Methods and compositions for treating thyroid eye disease

Abstract

Provided herein are methods and compositions for treating an individual having an insulin-like growth factor 1 receptor (IGF1R)-related disorder using an antagonist of IGF1R signaling.

Description

[0001] Cross-references

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 346,069, filed on May 26, 2022, and U.S. Provisional Application No. 63 / 386,528, filed on December 8, 2022, both of which are incorporated herein by reference in their entirety. Background Art

[0003] Insulin-like growth factor 1 receptor (IGF1R) is a cell surface receptor. IGF1R signaling is involved in many disorders, such as thyroid eye disease (TED), also known as Graves' eye disease, Graves' ophthalmopathy, Graves' orbitopathy, thyroid associated eye disease (TAO). Thyroid eye disease can affect the thyroid gland and the eye and cause inflammation and damage to the muscles and connective tissues of the eye, resulting in pain, swelling, defects in the eye socket, poor vision, or blindness.

[0004] There is a need for methods and compositions for treating IGF1R-associated disorders, such as thyroid eye disease.

[0005] Incorporation by Reference

[0006] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. Summary of the invention

[0007] In one aspect, provided herein is a method for treating an individual with an insulin-like growth factor 1 receptor (IGF1R)-associated disorder, the method comprising: a) selecting the individual for treatment with an antagonist of IGF1R signaling if the individual with the IGF1R-associated disorder exhibits normal glycemic control by a glycemic control test; and b) administering the antagonist of IGF1R signaling to the individual. In some embodiments, the IGF1R-associated disorder comprises thyroid eye disease. In some embodiments, the antagonist of IGF1R signaling comprises an antibody that binds to IGF1R. In some embodiments, the antibody that binds to IGF1R includes ganitumab, figitumumab, MEDI-573, cixutumumab, dalotuzumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumab or linsitinib. In some embodiments, the antibody that binds to IGF1R includes teprotumumab. In some embodiments, the antagonist of IGF1R signaling includes a small molecule that inhibits IGF1R signaling. In some embodiments, the small molecule that inhibits IGF1R signaling includes picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, ganetespib, ceritinib, or A-928605.In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising an amino acid sequence according to SEQ ID No.:5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising an amino acid sequence according to SEQ ID No.:6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising an amino acid sequence according to SEQ ID No.:7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising an amino acid sequence according to SEQ ID No.:8; (ii) a second light chain complementarity determining region (LCDR2) comprising an amino acid sequence according to SEQ ID No.:9; and (iii) a third light chain complementarity determining region (LCDR3) comprising an amino acid sequence according to SEQ ID No.:10. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence according to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence according to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence according to SEQ ID No.: 1; and b) a light chain comprising the amino acid sequence according to SEQ ID No.:2.

[0008] In some embodiments, the blood glucose control test comprises a measurement of hemoglobin A1c (HbA1c), an oral glucose tolerance test, a measurement of fasting blood glucose, a measurement of non-fasting blood glucose, or any combination thereof. In some embodiments, the blood glucose control test comprises a measurement of hemoglobin A1c (HbA1c). In some embodiments, if the measurement of hemoglobin A1c (HbA1c) is less than about 6.5%, the individual exhibits normal blood glucose control. In some embodiments, if the measurement of hemoglobin A1c (HbA1c) is less than about 5.7%, the individual exhibits normal blood glucose control. In some embodiments, the blood glucose control test comprises an oral glucose tolerance test. In some embodiments, if the individual exhibits a blood glucose level of less than about 200 mg / dL about two hours after oral intake of about 75 grams of sugar, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a blood glucose level of about 140 mg / dL or less about two hours after oral intake of about 75 grams of sugar, the individual exhibits normal blood glucose control. In some embodiments, the blood glucose control test comprises a measurement of fasting blood glucose. In some embodiments, if the individual exhibits a blood glucose level of less than about 126 mg / dL after an overnight fast, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a blood glucose level of about 99 mg / dL or less after an overnight fast, the individual exhibits normal blood glucose control. In some embodiments, the overnight fast lasts for at least about 8 hours. In some embodiments, the overnight fast lasts between about 8 and about 16 hours. In some embodiments, the blood glucose control test includes a measurement of non-fasting blood glucose. In some embodiments, if the individual exhibits a non-fasting blood glucose level of less than about 200 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, prior to treatment with the antagonist of IGF1R signaling, the individual was diagnosed as suffering from hyperglycemia, prediabetes, or diabetes. In some embodiments, the administration comprises intravenous infusion. In some embodiments, the administration comprises administering about 10 mg / kg of the antagonist of IGF1R signaling over a period of about 60 min to about 90 min, based on the individual's body weight. In some embodiments, the administering further comprises administering about 20 mg / kg of the antagonist of IGF1R signaling over the course of about 60 min to about 90 min based on the individual's body weight. In some embodiments, the administering further comprises administering about 20 mg / kg of the antagonist of IGF1R signaling once every 3 weeks for about 7 times.

[0009] In another aspect, provided herein is a method for treating an individual with an insulin-like growth factor 1 receptor (IGF1R)-related disorder, the method comprising: a) obtaining the results of a glycemic control test from the individual; and b) administering an antagonist of IGF1R signaling to the individual if the individual exhibits normal glycemic control by the glycemic control test. In some embodiments, the IGF1R-related disorder comprises thyroid eye disease. In some embodiments, the antagonist of IGF1R signaling comprises an antibody that binds to IGF1R. In some embodiments, the antibody that binds to IGF1R comprises ganitumab, figitumumab, MEDI-573, cixutumumab, dalotuzumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumab, or linsitinib. In some embodiments, the antibody that binds IGF1R comprises teprotumumab. In some embodiments, the antagonist of IGF1R signaling comprises a small molecule that inhibits IGF1R signaling. In some embodiments, the small molecule that inhibits IGF1R signaling includes picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, ganetespib, ceritinib, or A-928605.In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising an amino acid sequence according to SEQ ID No.:5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising an amino acid sequence according to SEQ ID No.:6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising an amino acid sequence according to SEQ ID No.:7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising an amino acid sequence according to SEQ ID No.:8; (ii) a second light chain complementarity determining region (LCDR2) comprising an amino acid sequence according to SEQ ID No.:9; and (iii) a third light chain complementarity determining region (LCDR3) comprising an amino acid sequence according to SEQ ID No.:10. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence according to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence according to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence according to SEQ ID No.: 1; and b) a light chain comprising the amino acid sequence according to SEQ ID No.: 2.

[0010] In some embodiments, the blood glucose control test comprises a measurement of hemoglobin A1c (HbA1c), an oral glucose tolerance test, a measurement of fasting blood glucose, a measurement of non-fasting blood glucose, or any combination thereof. In some embodiments, the blood glucose control test comprises a measurement of hemoglobin A1c (HbA1c). In some embodiments, if the measurement of the HbA1c is less than about 6.5%, the individual exhibits normal blood glucose control. In some embodiments, if the measurement of the HbA1c is less than about 5.7%, the individual exhibits normal blood glucose control. In some embodiments, the blood glucose control test comprises an oral glucose tolerance test. In some embodiments, if the individual exhibits a blood glucose level of less than about 200 mg / dL about two hours after oral intake of about 75 grams of sugar, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a blood glucose level of about 140 mg / dL or less about two hours after oral intake of about 75 grams of sugar, the individual exhibits normal blood glucose control. In some embodiments, the blood glucose control test comprises a measurement of fasting blood glucose. In some embodiments, if the individual exhibits a blood glucose level of less than about 126 mg / dL after an overnight fast, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a blood glucose level of about 99 mg / dL or less after an overnight fast, the individual exhibits normal blood glucose control. In some embodiments, the overnight fast lasts for at least about 8 hours. In some embodiments, the overnight fast lasts between about 8 and about 16 hours. In some embodiments, the blood glucose control test includes a measurement of non-fasting blood glucose. In some embodiments, if the individual exhibits a non-fasting blood glucose level of less than about 200 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, prior to treatment with the antagonist of IGF1R signaling, the individual was diagnosed as suffering from hyperglycemia, prediabetes, or diabetes. In some embodiments, the administration comprises intravenous infusion. In some embodiments, the administration comprises administering about 10 mg / kg of the antagonist of IGF1R signaling over a period of about 60 min to about 90 min, based on the individual's body weight. In some embodiments, the administering further comprises administering about 20 mg / kg of the antagonist of IGF1R signaling over the course of about 60 min to about 90 min based on the individual's body weight. In some embodiments, the administering further comprises administering about 20 mg / kg of the antagonist of IGF1R signaling once every 3 weeks for about 7 times.

[0011] In another aspect, provided herein is a method for monitoring an individual treated with an antagonist of insulin-like growth factor 1 receptor (IGF1R) signaling, wherein the individual suffers from an IGF1R-associated disorder, the method comprising: a) obtaining the results of a glycemic control test from the individual treated with the antagonist of IGF1R signaling; and b) interrupting treatment of the individual with the antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control as measured by the glycemic control test. In some embodiments, the IGF1R-associated disorder comprises thyroid eye disease. In some embodiments, the antagonist of IGF1R signaling comprises an antibody that binds to IGF1R. In some embodiments, the antibody that binds to IGF1R includes ganitumab, figitumumab, MEDI-573, cixutumumab, dalotuzumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumab or linsitinib. In some embodiments, the antibody that binds to IGF1R includes teprotumumab. In some embodiments, the antagonist of IGF1R signaling includes a small molecule that inhibits IGF1R signaling. In some embodiments, the small molecule that inhibits IGF1R signaling includes picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, ganetespib, ceritinib, or A-928605.In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising an amino acid sequence according to SEQ ID No.:5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising an amino acid sequence according to SEQ ID No.:6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising an amino acid sequence according to SEQ ID No.:7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising an amino acid sequence according to SEQ ID No.:8; (ii) a second light chain complementarity determining region (LCDR2) comprising an amino acid sequence according to SEQ ID No.:9; and (iii) a third light chain complementarity determining region (LCDR3) comprising an amino acid sequence according to SEQ ID No.:10. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence according to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence according to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence according to SEQ ID No.: 1; and b) a light chain comprising the amino acid sequence according to SEQ ID No.:2.

[0012] In some embodiments, the blood glucose control test comprises a measurement of hemoglobin A1c (HbA1c), an oral glucose tolerance test, a measurement of fasting blood glucose, a measurement of non-fasting blood glucose, or any combination thereof. In some embodiments, the blood glucose control test comprises a measurement of hemoglobin A1c (HbA1c). In some embodiments, if the measurement of the HbA1c is about 6.5% or higher, the individual exhibits abnormal blood glucose control. In some embodiments, if the measurement of the HbA1c is higher than about 5.7% or higher, the individual exhibits abnormal blood glucose control. In some embodiments, the blood glucose control test comprises an oral glucose tolerance test. In some embodiments, if the individual exhibits a blood glucose level of at least about 200 mg / dL about two hours after oral intake of about 75 grams of sugar, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual exhibits a blood glucose level higher than about 140 mg / dL about two hours after oral intake of about 75 grams of sugar, the individual exhibits abnormal blood glucose control. In some embodiments, the blood glucose control test comprises a measurement of fasting blood glucose. In some embodiments, if the measurement of the fasting blood glucose after an overnight fast is about 126 mg / dL or higher, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the fasting blood glucose after an overnight fast is higher than about 99 mg / dL, the individual exhibits abnormal glycemic control. In some embodiments, the overnight fast lasts at least about 8 hours. In some embodiments, the overnight fast lasts between about 8 and about 16 hours. In some embodiments, the glycemic control test includes a measurement of non-fasting blood glucose. In some embodiments, if the individual exhibits a non-fasting blood glucose level of about 200 mg / dL or higher, the individual exhibits abnormal glycemic control. In some embodiments, prior to treatment with the antagonist of IGF1R signaling, the individual is diagnosed with pre-existing hyperglycemia, prediabetes, or diabetes. In some embodiments, the administration comprises intravenous infusion. In some embodiments, the method further comprises obtaining the results of a second glycemic control test from the individual after treating the individual's abnormal glycemic control. In some embodiments, the method further comprises administering the antagonist of IGF1R signaling to the individual if the individual exhibits normal glycemic control by the second glycemic control test. In some embodiments, the administering further comprises administering about 10 mg / kg of the antagonist of IGF1R signaling based on the individual's body weight. In some embodiments, the administering further comprises administering about 20 mg / kg of the antagonist of IGF1R signaling based on the individual's body weight once every 3 weeks for about 7 times.

[0013] In another aspect, provided herein is a method for treating an individual with an insulin-like growth factor 1 receptor (IGF1R)-associated disorder, the method comprising: a) administering to the individual a first dose of an antagonist of IGF1R signaling; b) obtaining the results of a glycemic control test from the individual; and c) if the individual exhibits abnormal glycemic control by the glycemic control test, administering to the individual a second dose of the antagonist of IGF1R signaling, wherein the second dose is lower than the first dose. In some embodiments, the IGF1R-associated disorder comprises thyroid eye disease. In some embodiments, the antagonist of IGF1R signaling comprises an antibody that binds to IGF1R. In some embodiments, the antibody that binds to IGF1R includes ganitumab, figitumumab, MEDI-573, cixutumumab, dalotuzumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumab or linsitinib. In some embodiments, the antibody that binds to IGF1R includes teprotumumab. In some embodiments, the antagonist of IGF1R signaling includes a small molecule that inhibits IGF1R signaling. In some embodiments, the small molecule that inhibits IGF1R signaling includes picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, or A-928605.In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising an amino acid sequence according to SEQ ID No.:5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising an amino acid sequence according to SEQ ID No.:6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising an amino acid sequence according to SEQ ID No.:7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising an amino acid sequence according to SEQ ID No.:8; (ii) a second light chain complementarity determining region (LCDR2) comprising an amino acid sequence according to SEQ ID No.:9; and (iii) a third light chain complementarity determining region (LCDR3) comprising an amino acid sequence according to SEQ ID No.:10. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence according to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence according to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence according to SEQ ID No.: 1; and b) a light chain comprising the amino acid sequence according to SEQ ID No.:2.

[0014] In some embodiments, the blood glucose control test comprises a measurement of hemoglobin A1c (HbA1c), an oral glucose tolerance test, a measurement of fasting blood glucose, a measurement of non-fasting blood glucose, or any combination thereof. In some embodiments, the blood glucose control test comprises a measurement of hemoglobin A1c (HbA1c). In some embodiments, if the measurement of the HbA1c is about 6.5% or higher, the individual exhibits abnormal blood glucose control. In some embodiments, if the measurement of the HbA1c is about 5.7% or higher, the individual exhibits abnormal blood glucose control. In some embodiments, the blood glucose control test comprises an oral glucose tolerance test. In some embodiments, if the individual exhibits a blood glucose level of about 200 mg / dL or higher about two hours after oral intake of about 75 grams of sugar, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual exhibits a blood glucose level of greater than about 140 mg / dL about two hours after oral intake of about 75 grams of sugar, the individual exhibits abnormal blood glucose control. In some embodiments, the blood glucose control test comprises a measurement of fasting blood glucose. In some embodiments, if the measurement of the fasting blood glucose after an overnight fast is about 126 mg / dL or higher, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the fasting blood glucose after an overnight fast is higher than about 99 mg / dL, the individual exhibits abnormal glycemic control. In some embodiments, the overnight fast lasts at least about 8 hours. In some embodiments, the overnight fast lasts between about 8 and about 16 hours. In some embodiments, the glycemic control test includes the measurement of non-fasting blood glucose. In some embodiments, if the individual exhibits a non-fasting blood glucose level of about 200 mg / dL or higher, the individual exhibits abnormal glycemic control. In some embodiments, prior to treatment with the antagonist of IGF1R signaling, the individual was diagnosed with pre-existing hyperglycemia, prediabetes or diabetes. In some embodiments, the administration comprises intravenous infusion. In some embodiments, the first dose comprises about 10 mg / kg of the antagonist of IGF1R signaling administered over the course of about 60 min to about 90 min based on the individual's body weight. In some embodiments, the first dose further comprises about 20 mg / kg of the antagonist of IGF1R signaling administered over the course of about 60 min to about 90 min based on the individual's body weight. In some embodiments, the about 20 mg / kg of the antagonist of IGF1R signaling is administered to the individual once every 3 weeks for about 7 times.

[0015] In another aspect, provided herein is a method for treating an individual with an insulin-like growth factor 1 receptor (IGF1R)-related disorder, the method comprising: a) selecting the individual for treatment with an antagonist of IGF1R signaling if the individual with the IGF1R-related disorder exhibits normal glycemic control by a first glycemic control test; b) administering a first dose of the antagonist of IGF1R signaling to the individual; and c) obtaining the results of a second glycemic control test from the individual treated with the antagonist of IGF1R signaling. In some embodiments, the method further comprises interrupting treatment of the individual with the antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control by the results of the second glycemic control test. In some embodiments, the method further comprises administering a second dose of the antagonist of IGF1R signaling to the individual if the individual exhibits abnormal glycemic control by the results of the second glycemic control test. In some embodiments, the IGF1R-related disorder comprises thyroid eye disease. In some embodiments, the antagonist of IGF1R signaling comprises an antibody that binds to IGF1R. In some embodiments, the antibody that binds to IGF1R includes ganitumab, figitumumab, MEDI-573, cixutumumab, dalotuzumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumab or linsitinib. In some embodiments, the antibody that binds to IGF1R includes teprotumumab. In some embodiments, the antagonist of IGF1R signaling includes a small molecule that inhibits IGF1R signaling. In some embodiments, the small molecule that inhibits IGF1R signaling includes picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, or A-928605.In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising an amino acid sequence according to SEQ ID No.:5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising an amino acid sequence according to SEQ ID No.:6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising an amino acid sequence according to SEQ ID No.:7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising an amino acid sequence according to SEQ ID No.:8; (ii) a second light chain complementarity determining region (LCDR2) comprising an amino acid sequence according to SEQ ID No.:9; and (iii) a third light chain complementarity determining region (LCDR3) comprising an amino acid sequence according to SEQ ID No.:10. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence according to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence according to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence according to SEQ ID No.: 1; and b) a light chain comprising the amino acid sequence according to SEQ ID No.:2.

[0016] In some embodiments, the first or second glycemic control test comprises a measurement of hemoglobin A1c (HbA1c), an oral glucose tolerance test, a measurement of fasting blood glucose, a measurement of non-fasting blood glucose, or any combination thereof. In some embodiments, the first or second glycemic control test comprises a measurement of hemoglobin A1c (HbA1c). In some embodiments, if the measurement of HbA1c is about 6.5% or higher, the individual exhibits abnormal glycemic control, wherein if the measurement of hemoglobin A1c (HbA1c) is below about 6.5%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of HbA1c is about 5.7% or higher, the individual exhibits abnormal glycemic control, wherein if the measurement of hemoglobin A1c (HbA1c) is below about 5.7%, the individual exhibits normal glycemic control. In some embodiments, the glycemic control test comprises an oral glucose tolerance test. In some embodiments, if the individual shows a blood glucose level of at least about 200 mg / dL about two hours after oral intake of about 75 grams of sugar, the individual shows abnormal blood glucose control, wherein if the individual shows a blood glucose level of less than about 200 mg / dL about two hours after oral intake of about 75 grams of sugar, the individual shows normal blood glucose control. In some embodiments, if the individual shows a blood glucose level higher than about 140 mg / dL about two hours after oral intake of 75 grams of sugar, the individual shows abnormal blood glucose control, wherein if the individual shows a blood glucose level of about 140 mg / dL or less about two hours after oral intake of about 75 grams of sugar, the individual shows normal blood glucose control. In some embodiments, the blood glucose control test includes the measurement of fasting blood glucose. In some embodiments, if the measurement of the fasting blood glucose is about 126 mg / dL or higher after fasting overnight, the individual shows abnormal blood glucose control, wherein if the individual shows a blood glucose level lower than about 126 mg / dL after fasting overnight, the individual shows normal blood glucose control. In some embodiments, if the measurement of the fasting blood glucose after fasting overnight is higher than about 99 mg / dL, the individual exhibits abnormal blood glucose control, wherein if the individual exhibits a blood glucose level of about 99 mg / dL or lower after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, the fasting overnight lasts at least about 8 hours. In some embodiments, the fasting overnight lasts between about 8 and about 16 hours. In some embodiments, the blood glucose control test includes the measurement of non-fasting blood glucose. In some embodiments, if the individual exhibits a non-fasting blood glucose level of about 200 mg / dL or higher, the individual exhibits abnormal blood glucose control, wherein if the individual exhibits a non-fasting blood glucose level lower than about 200 mg / dL, the individual exhibits normal blood glucose control.In some embodiments, prior to treatment with the antagonist of IGF1R signaling, the individual is diagnosed with pre-existing hyperglycemia, prediabetes, or diabetes. In some embodiments, the administration comprises an intravenous infusion. In some embodiments, the first dose comprises about 10 mg / kg of the antagonist of IGF1R signaling administered over the course of about 60 min to about 90 min based on the individual's body weight. In some embodiments, the first dose further comprises about 20 mg / kg of the antagonist of IGF1R signaling administered over the course of about 60 min to about 90 min based on the individual's body weight. In some embodiments, the about 20 mg / kg of the antagonist of IGF1R signaling is administered to the individual once every 3 weeks for 7 times. In some embodiments, the method further comprises treating the individual's abnormal blood control if the individual exhibits abnormal blood glucose control as determined by the result of the second blood glucose control test.

[0017] In one aspect, described herein is a method for treating an individual with an insulin-like growth factor 1 receptor (IGF1R)-related disorder, the method comprising: a) obtaining the results of a blood glucose test from the individual; and b) if the individual does not exhibit elevated blood glucose by the blood glucose test, administering to the individual a dose of an antagonist of IGF1R signaling. In certain embodiments, the IGF1R-related disorder comprises thyroid eye disease. In certain embodiments, the antagonist of IGF1R signaling comprises an antibody that binds to IGF1R. In certain embodiments, the antibody that binds to IGF1R comprises ganituzumab, fentolumab, MEDI-573, situmumab, darototumumab, rotumumab, AVE1642, BIIB022, zhentuzumab, estuzumab or lincitinib. In certain embodiments, the antibody that binds to IGF1R comprises tetotutumumab. In certain embodiments, the antagonist of IGF1R signaling comprises a small molecule that inhibits IGF1R signaling. In certain embodiments, the small molecule that inhibits IGF1R signaling includes picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, or A-928605. In certain embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising an amino acid sequence according to SEQ ID No.:5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising an amino acid sequence according to SEQ ID No.:6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising an amino acid sequence according to SEQ ID No.:7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising an amino acid sequence according to SEQ ID No.:8; (ii) a second light chain complementarity determining region (LCDR2) comprising an amino acid sequence according to SEQ ID No.:9; and (iii) a third light chain complementarity determining region (LCDR3) comprising an amino acid sequence according to SEQ ID No.:10.In certain embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 4. In certain embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence according to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence according to SEQ ID No.: 4. In certain embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 2. In certain embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising an amino acid sequence according to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence according to SEQ ID No.: 2. In certain embodiments, the blood glucose test comprises a measurement of hemoglobin A1c (HbA1c), an oral glucose tolerance test, a measurement of fasting blood glucose, a measurement of non-fasting blood glucose, or any combination thereof. In certain embodiments, the blood glucose test comprises a measurement of hemoglobin A1c (HbA1c). In certain embodiments, if the measurement of HbA1c is about 6.5% or less, the individual does not exhibit elevated blood glucose. In certain embodiments, if the measurement of HbA1c is about 5.7% or less, the individual does not exhibit elevated blood glucose. In certain embodiments, the blood glucose test comprises an oral glucose tolerance test. In certain embodiments, if the individual exhibits a blood glucose level of less than 200 mg / dL after about two hours after oral ingestion of about 75 grams of sugar, the individual does not exhibit elevated blood glucose. In certain embodiments, if the individual shows a blood glucose level lower than 140mg / dL after about two hours after oral intake of about 75 grams of sugar, the individual does not show elevated blood glucose. In certain embodiments, the blood glucose test includes the measurement of fasting blood glucose. In certain embodiments, if the measurement of the fasting blood glucose is lower than 126mg / dL after fasting overnight, the individual does not show elevated blood glucose. In certain embodiments, if the measurement of the fasting blood glucose is lower than 99mg / dL after fasting overnight, the individual does not show elevated blood glucose. In certain embodiments, the fasting overnight continues at least about 8 hours. In certain embodiments, the fasting overnight continues between about 8 and about 16 hours. In certain embodiments, the blood glucose test includes the measurement of non-fasting blood glucose.In certain embodiments, the individual does not exhibit elevated blood glucose if the individual exhibits a non-fasting blood glucose level of less than about 200 mg / dL. In certain embodiments, the individual was diagnosed with pre-existing hyperglycemia, prediabetes, or diabetes prior to treatment with the antagonist of IGF1R signaling. In certain embodiments, the administration comprises intravenous infusion. In certain embodiments, the dose comprises about 10 mg / kg of the antagonist of IGF1R signaling administered over a period of about 60 min to about 90 min based on the individual's body weight. In certain embodiments, the dose comprises about 20 mg / kg of the antagonist of IGF1R signaling administered over a period of about 60 min to about 90 min based on the individual's body weight. In certain embodiments, the about 20 mg / kg of the antagonist of IGF1R signaling is administered to the individual once every 3 weeks for about 7 times.

[0018] In another aspect, a method of treating an individual with an insulin-like growth factor 1 receptor (IGF1R)-related disorder, wherein the individual also has diabetes, is described herein, comprising: (a) administering one or more antidiabetic drugs to lower blood glucose levels; and (b) administering to the individual a dose of an antagonist of IGF1R signaling. In certain embodiments, the IGF1R-related disorder comprises thyroid eye disease. In certain embodiments, the antagonist of IGF1R signaling comprises an antibody that binds to IGF1R. In certain embodiments, the antibody that binds to IGF1R comprises ganituzumab, fentolumab, MEDI-573, situmumab, darototumumab, rotumumab, AVE1642, BIIB022, zhentuzumab, estuzumab or lincitinib. In certain embodiments, the antibody that binds to IGF1R comprises tetotumumab. In certain embodiments, the antagonist of IGF1R signaling comprises a small molecule that inhibits IGF1R signaling. In certain embodiments, the small molecule that inhibits IGF1R signaling includes picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, or A-928605. In certain embodiments, the antibody that binds to IGF1R comprises: (a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising an amino acid sequence according to SEQ ID No.:5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising an amino acid sequence according to SEQ ID No.:6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising an amino acid sequence according to SEQ ID No.:7; and (b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising an amino acid sequence according to SEQ ID No.:8; (ii) a second light chain complementarity determining region (LCDR2) comprising an amino acid sequence according to SEQ ID No.:9; and (iii) a third light chain complementarity determining region (LCDR3) comprising an amino acid sequence according to SEQ ID No.:10.In certain embodiments, the antibody that binds to IGF1R comprises: (a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and (b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 4. In certain embodiments, the antibody that binds to IGF1R comprises: (a) a heavy chain variable domain comprising an amino acid sequence according to SEQ ID No.: 3; and (b) a light chain variable domain comprising an amino acid sequence according to SEQ ID No.: 4. In certain embodiments, the antibody that binds to IGF1R comprises: (a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and (b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 2. V The antibody that binds to IGF1R comprises: (a) a heavy chain comprising an amino acid sequence according to SEQ ID No.: 1; and (b) a light chain comprising an amino acid sequence according to SEQ ID No.: 2. In certain embodiments, the one or more antidiabetic drugs are selected from the list consisting of: insulin, metformin, pioglitazone, rosiglitazone, acarbose, miglitol, bromocriptine, alogliptin, linagliptin, saxagliptin, sitagliptin, dulaglutide, exenatide, Liraglutide, lixisenatide, semaglutide, tirzepatide, nateglinide, repaglinide, canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, glimepiride, gliclazide, glipizide, and combinations thereof. In certain embodiments, blood glucose levels are established by measurement of hemoglobin A1c (HbA1c), oral glucose tolerance test, measurement of fasting blood glucose, measurement of non-fasting blood glucose, or any combination thereof. In certain embodiments, the administration comprises intravenous infusion.In certain embodiments, the dosage comprises about 10 mg / kg of the antagonist of IGF1R signaling administered over a period of about 60 min to about 90 min based on the individual's body weight. In certain embodiments, the dosage comprises about 20 mg / kg of the antagonist of IGF1R signaling administered over a period of about 60 min to about 90 min based on the individual's body weight. In certain embodiments, the about 20 mg / kg of the antagonist of IGF1R signaling is administered to the individual once every 3 weeks for about 7 times. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The novel features of the present disclosure are particularly set forth in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by referring to the following detailed description and accompanying drawings which illustrate illustrative embodiments utilizing the principles of the present invention, in which:

[0020] Figure 1 Examples of methods for treating an individual suffering from an IGF1R-related disorder with an antagonist of IGF1R signaling are described. DETAILED DESCRIPTION

[0021] Unless otherwise indicated, the present disclosure employs conventional biological and medical techniques, which are within the capabilities of those skilled in the art. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by those of ordinary skill in the art.

[0022] definition

[0023] Throughout this disclosure, various embodiments are presented in the form of ranges. It should be understood that the description of the range form is only for convenience and simplicity, and should not be interpreted as an inflexible limitation on the scope of any embodiment. Therefore, unless the context clearly stipulates otherwise, the description of the range should be considered to specifically disclose all possible sub-ranges and each numerical value accurate to one-tenth of the lower limit unit within this range. For example, the description of the range such as from 1 to 6 should be considered to have specifically disclosed a sub-range, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and a single value within this range, for example, 1.1, 2, 2.3, 5 and 5.9. Regardless of the width of the range, this is applicable. The upper and lower limits of these intermediate ranges can be independently included in a smaller range, and are also included in this disclosure, subject to any specifically excluded restrictions within the scope. Unless the context clearly stipulates otherwise, in the case where the range includes one or both of the limits, the scope excluding any one or both of these included limits is also included in this disclosure.

[0024] The specialized terms used herein are for the purpose of describing specific embodiments only and are not intended to limit any embodiment. Unless the context clearly indicates otherwise, as used herein, the singular forms "a", "an", and "the" are also intended to include the plural forms. It will also be understood that the terms "comprises" and / or "comprising", when used in this specification, specify the presence of the features, integers, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof. As used herein, the term "and / or" includes any and all combinations of one or more of the relevant listed items.

[0025] Unless otherwise specified or apparent from the context, as used herein, the term "about" in reference to a numerical value or range of values ​​should be understood to mean the stated value and its value + / - 10%, or 10% below the listed lower limit and 10% above the listed upper limit of the value listed in the range.

[0026] As used herein, the terms "individual," "patient," or "subject" refer to an individual diagnosed with, suspected of having, or at risk of developing at least one disease for which the described compositions and methods can be used to treat. In certain embodiments, the individual is a mammal. In certain embodiments, the mammal is a mouse, rat, rabbit, dog, cat, horse, cow, sheep, pig, goat, llama, alpaca, or yak. ​​In certain embodiments, the individual is a human.

[0027] The term "antibody" herein is used in the broadest sense and includes monoclonal antibodies, and includes complete antibodies and functional (antigen-binding) antibody fragments thereof, including the following fragments: antigen-binding (Fab) fragments, F(ab')2 fragments, Fab' fragments, Fv fragments, recombinant IgG (rIgG) fragments, single-chain antibody fragments (including single-chain variable fragments (sFv or scFv)) and single-domain antibodies (e.g., sdAb, sdFv, nanobody) fragments. The term encompasses genetically engineered and / or otherwise modified forms of immunoglobulins, such as intracellular antibodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies and heteroconjugate antibodies, multispecific (e.g., bispecific) antibodies, double antibodies, three antibodies and four antibodies, tandem two-scFv, tandem three-scFv. Unless otherwise indicated, the term "antibody" should be understood to encompass functional antibody fragments thereof. The term also encompasses intact or full-length antibodies, including antibodies of any class or subclass, including IgG and its subclasses, IgM, IgE, IgA and IgD. The antibody may comprise a human IgG1 constant region. The antibody may comprise a human IgG4 constant region.

[0028] The terms "complementarity determining region" and "CDR" (which are synonymous with "hypervariable region" or "HVR") are known in the art to refer to non-contiguous amino acid sequences within an antibody variable region that confer antigen specificity and / or binding affinity. Typically, there are three CDRs (CDR-H1, CDR-H2, CDR-H3) in each heavy chain variable region, and three CDRs (CDR-L1, CDR-L2, CDR-L3) in each light chain variable region. "Framework region" and "FR" are known in the art to refer to the non-CDR portions of the variable regions of the heavy and light chains. Typically, there are four FRs (FR-H1, FR-H2, FR-H3, and FR-H4) in each full-length heavy chain variable region, and four FRs (FR-L1, FR-L2, FR-L3, and FR-L4) in each full-length light chain variable region.The precise amino acid sequence boundaries of a given CDR or FR can be readily determined using any of a number of well-known schemes, including those described by Kabat et al. (1991), "Sequences of Proteins of Immunological Interest," 5th Edition, Public Health Service, National Institutes of Health, Bethesda, MD ("Kabat" numbering scheme), Al-Lazikani et al., (1997) JMB 273, 927-948 ("Chothia" numbering scheme); MacCallum et al., J. Mol. Biol. [Journal of Molecular Biology] 262:732-745 (1996), "Antibody-antigen interactions: Contact analysis and binding site topography [Antibody-antigen interactions: contact analysis and binding site topography]," J. Mol. Biol. [Journal of Molecular Biology] 262, 732-745. ("Contact" numbering scheme); Lefranc MP et al., "IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains," Dev Comp Immunol [Development and Comparative Immunology], 2003 Jan; 27(1): 55-77 ("IMGT" numbering scheme); Honegger A and Plückthun A, "Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool [Immunoglobulin variable domains]," J Mol Biol, 2001 Jun 8;309(3):657-70, ("Aho" numbering scheme); and. Whitelegg NR and Rees AR,“WAM: an improved algorithm for modelling antibodies on the WEB,” Protein Eng .[Protein Engineering] 2000 Dec; 13(12):819-24 ("AbM" numbering scheme). In certain embodiments, the CDRs of the antibodies described herein can be defined by a method selected from the group consisting of Kabat, Chothia, IMGT, Aho, AbM, or a combination thereof.

[0029] The boundary of a given CDR or FR may differ according to the scheme used for identification. For example, the Kabat scheme is based on structural alignment, and the Chothia scheme is based on structural information. The numbering of the Kabat and Chothia schemes is based on the most common antibody region sequence length, with the insertion provided by inserting letters (e.g., "30a") and the disappearance occurring in some antibodies. These two schemes place certain insertions and deletions ("indels") in different positions, thereby producing difference numbering. The Contact scheme is based on the analysis of complex crystal structures, and is similar to the Chothia numbering scheme in many respects.

[0030] The term "variable region" or "variable domain" refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to an antigen. The variable domains of the heavy and light chains of a native antibody (V H and V L ) generally have a similar structure, wherein each domain comprises four conserved framework regions (FRs) and three CDRs (see, e.g., Kindt et al. Kuby Immunology, 6th ed., WH Freeman and Co., p. 91 (2007)). A single V H or V L A domain may be sufficient to confer antigen binding specificity. In addition, antibodies that bind to a specific antigen may use a V H or V L The domains are separated from antibodies that bind to the antigen to screen for complementary V L or V H Libraries of domains (see, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991)).

[0031] The specific binding or binding of antibody molecules described herein refers to the binding mediated by one or more CDR portions of the antibody. Not all CDRs are necessary for specific binding. Specific binding can be demonstrated, for example, by ELISA for a specific target or antigen listed, which shows a significant increase in binding compared to an isotype control antibody.

[0032] Among the antibodies provided are antibody fragments. An "antibody fragment" refers to a molecule other than an intact antibody that contains a portion of an intact antibody that binds to an antigen to which the intact antibody binds. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab', Fab'-SH, F(ab')2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv or sFv); and multispecific antibodies formed from antibody fragments. In a specific embodiment, the antibody is a single-chain antibody fragment (such as, scFv) comprising a variable heavy chain region and / or a variable light chain region.

[0033] Antibody fragments can be prepared by a variety of techniques, including but not limited to proteolytic digestion of intact antibodies and production by recombinant host cells. In some embodiments, antibodies are recombinantly produced fragments, such as fragments comprising non-naturally occurring rearrangements, such as those having two or more antibody regions or chains joined by synthetic linkers (e.g., polypeptide linkers), and / or those not produced by enzymatic digestion of naturally occurring intact antibodies. In some aspects, antibody fragments are scFv.

[0034] "Humanized" antibody is an antibody in which all or substantially all CDR amino acid residues are derived from non-human CDR and all or substantially all FR amino acid residues are derived from human FR. Humanized antibodies optionally may include at least a portion of an antibody constant region derived from a human antibody. "Humanized form" of a non-human antibody refers to a variant of a non-human antibody that has undergone humanization, typically to reduce immunogenicity to people, while retaining the specificity and affinity of the parent non-human antibody. In certain embodiments, some FR residues in a humanized antibody are replaced by corresponding residues from a non-human antibody (e.g., an antibody derived from CDR residues), such as to restore or improve antibody specificity or affinity.

[0035] Among the antibodies provided are human antibodies. A "human antibody" is an antibody whose amino acid sequence corresponds to that of an antibody produced by a human or human cell or a non-human source utilizing a human antibody library or other human antibody encoding sequences (including human antibody libraries). The term excludes humanized forms of non-human antibodies comprising non-human antigen binding regions, such as those in which all or substantially all CDRs are non-human.

[0036] Human antibodies can be prepared by administering an immunogen to a transgenic animal that has been modified to produce complete human antibodies or complete antibodies with human variable regions in response to antigenic stimulation. Such animals typically contain all or part of a human immunoglobulin locus, which replaces an endogenous immunoglobulin locus, or it exists outside the chromosome or is randomly integrated into the chromosome of the animal. In such transgenic animals, the endogenous immunoglobulin locus is usually inactivated. Human antibodies can also be derived from human antibody libraries, including phage display and cell-free libraries, which contain antibody coding sequences derived from human libraries.

[0037] The terms "polypeptide" and "protein" are used interchangeably and refer to polymers of amino acid residues, and are not limited to a minimum length. Polypeptides (including antibodies and antibody chains provided and other peptides, such as linkers and binding peptides) may contain amino acid residues, including natural and / or non-natural amino acid residues. These terms also include post-expression modifications of polypeptides, such as glycosylation, sialylation, acetylation, phosphorylation, etc. In some aspects, these polypeptides may contain modifications relative to natural or native sequences, as long as the protein maintains the desired activity. These modifications may be intentional (such as by site-directed mutagenesis), or may be accidental (such as by mutations in the host producing the protein or errors caused by PCR amplification).

[0038] In some embodiments, it is contemplated that the amino acid sequence variants of the antibodies provided herein. The variants are typically different from the polypeptides particularly disclosed herein in terms of one or more substitutions, deletions, additions and / or insertions. Such variants may be naturally occurring or may be synthetically generated, for example, by modifying one or more of the above polypeptide sequences of the present invention and evaluating one or more biological activities of the polypeptides as described herein and / or using any of a variety of known techniques. For example, it may be desirable to improve the binding affinity and / or other biological properties of the antibody. The amino acid sequence variants of the antibody may be prepared by introducing appropriate modifications into the nucleotide sequence encoding the antibody or by peptide synthesis. Such modifications include, for example, the deletion of residues in the amino acid sequence of the antibody, and / or insertion and / or substitution. Any combination of deletions, insertions and substitutions may be performed to obtain the final construct, provided that the final construct has the desired characteristics, such as antigen binding.

[0039] The percentage of sequence identity (%) relative to a reference polypeptide sequence is to achieve the maximum percentage of sequence identity and not to consider any conservative substitution as part of sequence identity and to align the sequences and introduce a gap (if necessary), the percentage of the amino acid residues in the candidate sequence that are identical to the amino acid residues in the reference polypeptide sequence. The comparison for determining the percentage of amino acid sequence identity can be achieved in a known variety of ways, for example, using publicly available computer software, such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. It is possible to determine the appropriate parameters for aligning sequences, including the algorithm required for achieving maximum alignment on the full length of the sequence being compared. However, for the purposes of this article, the amino acid sequence identity % value is generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program is created by Genentech, Inc., and the source code has been submitted to the U.S. Copyright Office (USCopyright Office) (Washington DC 20559) together with user documentation, and registered in the U.S. Copyright Office with U.S. Copyright Registration Number TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc., South San Francisco, California, or can be compiled from source code. The ALIGN-2 program should be compiled for use on a UNIX operating system, including digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not change.

[0040] Where ALIGN-2 is used for amino acid sequence comparison, the % amino acid sequence identity of a given amino acid sequence A to, with or relative to a given amino acid sequence B (which may alternatively be phrased as a given amino acid sequence A having or comprising a certain % amino acid sequence identity to, with or relative to a given amino acid sequence B) is calculated as follows: the fraction X / Y multiplied by 100, where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in this program's alignment of A and B, and where Y is the total number of amino acid residues in B. It should be understood that if the length of amino acid sequence A is not equal to the length of amino acid sequence B, then the % amino acid sequence identity of A to B will not be equal to the % amino acid sequence identity of B to A. Unless expressly stated otherwise, all % amino acid sequence identity values ​​used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program.

[0041] As described herein, a "glycemic control test" is any test that can accurately measure an individual's blood glucose. Such tests can utilize personal glucose monitors, such as those compatible with diabetic test strips or insulin pumps; continuous glucose monitors, and laboratory glucose analyzers and automated analyzers used by hospitals and laboratory contractors. Such glycemic control tests include, but are not limited to, measurement of fasting blood glucose, measurement of non-fasting blood glucose, oral glucose tolerance test, or measurement of glycosylated hemoglobin A1c (HbA1c).

[0042] As used herein, "treat", "treatment" or "treating" refers to, for example, an intentional intervention in a physiological disease state, such that the severity of the disease or condition is reduced; the duration of the disease process is reduced; one or more symptoms associated with the disease or condition are improved or eliminated; or a beneficial effect is provided to a subject suffering from the disease or condition. Treatment does not require a cure of the underlying disease or condition. As used herein, with respect to thyroid eye disease, treatment can result in a reduction in the clinical activity score (CAS). This reduction can be a reduction of 1, 2, 3, 4, 5, 6 or more points.

[0043] Normal blood sugar control (when not present) can be achieved by any appropriate means, including but not limited to diet, exercise, or treatment with biguanides, insulin, DPP4 inhibitors, GLP-1 receptor agonists, meglitinides, sulfonylureas, thiazolidinediones, SGLT2 inhibitors, alpha-glucosidase inhibitors, or any combination thereof. Normal blood sugar can be established by administering insulin by a physician or by the patient himself prior to administering an IGF1R inhibitor.

[0044] A "therapeutically effective amount," "effective dose," "effective amount," or "therapeutically effective dose" of a drug or therapeutic agent is any amount of the drug, when used alone or in combination with another therapeutic agent, that protects a subject from the onset of a disease or promotes regression of a disease as evidenced by a reduction in the severity of disease symptoms, an increase in the frequency and duration of disease symptom-free periods, or the prevention of impairment or disability due to the disease distress. The ability of a therapeutic agent to promote regression of a disease can be evaluated using a variety of methods known to skilled practitioners, such as in human subjects during clinical trials, in animal model systems predictive of efficacy in humans, or by measuring the activity of the agent in in vitro assays.

[0045] As used herein, "pharmaceutically acceptable carriers, excipients or diluents" include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, etc. that are physiologically compatible. In some aspects, the carrier is suitable for intravenous, intramuscular, subcutaneous, parenteral, spinal or epidermal administration (e.g., by injection or infusion). Depending on the route of administration, the active compound (i.e., antibody) can be coated in a material to protect the compound from the action of acids and other natural conditions that can inactivate the compound.

[0046] Methods and compositions for treating IGF1R-related disorders

[0047] Insulin-like growth factor 1 receptor (IGF1R) is expressed on the surface of many cell types. IGF1R belongs to the insulin receptor family and has tyrosine kinase activity. IGF1R signaling is involved in disease disorders, including thyroid eye disease (TED), also known as Graves' eye disease, Graves' ophthalmopathy, Graves' orbitopathy, thyroid associated eye disease (TAO). Thyroid eye disease is an autoimmune disease and may cause inflammation and damage to the muscles and connective tissues of the eye. Symptoms of thyroid eye disease can include eye swelling, orbital defects, poor vision, and blindness. IGF1R related disorders can be treated with antagonists of IGF1R signaling.

[0048] Thyroid eye disease can be assessed by the clinical activity score (CAS) described in Mourits et al., British Journal of Ophthalmology, 1989, 73, No. 8, 639-644 as a way to assess the extent of active disease. The score based on the typical signs of acute inflammation (pain, redness, swelling, and impaired function) is proposed as a clinical classification to easily distinguish active disease from inactive disease, and was revised in 1997 (Mourits et al., Clinical Endocrinology, 1997.47, No. 1, 9-14). CAS consists of seven parts: spontaneous retrobulbar pain, pain when attempting eye movement (upward, left and right, and downward gaze), conjunctival redness, eyelid redness, conjunctival edema, swelling of the tear caruncle / folds, and eyelid swelling. Each part is scored as presence (1 point) or absence (0 points). The score for each efficacy assessment is the sum of all items present; a range of 0-7 is given, with 0 or 1 constituting inactive disease and 7 constituting severely active eye disease. The CAS score can distinguish active from inactive TED. An individual's quality of life can be measured using a self-assessment questionnaire, such as the Graves' ophthalmopathy quality of life (GO-QoL) questionnaire. See, e.g., Terwee CB, Gerding MN, Dekker FW, Prummel MF, Wiersinga WM. Development of adisease specific quality of life questionnaire for patients with Graves' ophthalmopathy: the GO-QoL. Br J Ophthalmol. 1998 Jul;82(7):773-9.

[0049] In certain embodiments, individuals are also selected for treatment by CAS, and individuals with lower CAS may have treatment delayed. In certain embodiments, individuals have a CAS of 3 or less, 2 or less, 1 or less, or 0. Treatment may be delayed until normoglycemia is established. Individuals with inactive or non-inflammatory TED may have treatment delayed until normoglycemic control is established.

[0050] On the one hand, the present invention provides a method for diagnosing, treating or monitoring an individual with an insulin-like growth factor 1 receptor (IGF1R)-related disorder. In some embodiments, the method includes one or more steps disclosed herein. In some embodiments, the method includes one or more, but not all, of the steps disclosed herein. Figure 1 is a diagram of one embodiment of the method 100. The processes, steps, components and parts of the method 100 are for illustrative purposes only and should not be interpreted in any way as limiting the scope of the method disclosed herein.

[0051] In some embodiments, the method includes a step 102 of obtaining the results of a first glycemic control test from an individual with an IGF1R-associated disorder. In some embodiments, the method includes a step 104 of selecting an individual with an IGF1R-associated disorder for treatment with an antagonist of IGF1R signaling. In some embodiments, the method includes selecting an individual with an IGF1R-associated disorder for treatment with an antagonist of IGF1R signaling based on the results of the first glycemic control test. In some embodiments, the method includes selecting an individual with an IGF1R-associated disorder for treatment with an antagonist of IGF1R signaling if the individual with the IGF1R-associated disorder exhibits normal glycemic control by the first glycemic control test. In some embodiments, the method includes selecting an individual with an IGF1R-associated disorder for treatment with an antagonist of IGF1R signaling if the individual with the IGF1R-associated disorder exhibits abnormal glycemic control by the first glycemic control test. In some embodiments, the method includes treating the individual for abnormal glycemic control prior to selecting the individual with an IGF1R-associated disorder for treatment with an antagonist of IGF1R signaling. In some embodiments, the treatment of the abnormal glycemic control includes any suitable treatment, including but not limited to insulin therapy.

[0052] In some embodiments, the method includes step 106 of administering to the individual a first dose of an antagonist of IGF1R signaling. In some embodiments, the method includes administering to the individual a first dose of an antagonist of IGF1R signaling based on the results of a first glycemic control test. In some embodiments, the method includes administering to the individual a first dose of an antagonist of IGF1R signaling if the individual exhibits normal glycemic control by the first glycemic control test. In some embodiments, the method includes administering to the individual a first dose of an antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control by the first glycemic control test. In some embodiments, the method includes treating the individual's abnormal glycemic control prior to administering to the individual a first dose of an antagonist of IGF1R signaling.

[0053] In some embodiments, the method includes step 108 of obtaining the results of a second glycemic control test from the individual treated with the first dose of the antagonist of IGF1R signaling. In some embodiments, the method includes step 110 of discontinuing treatment of the individual with the first dose of the antagonist of IGF1R signaling. In some embodiments, the method includes discontinuing treatment of the individual with the first dose of the antagonist of IGF1R signaling based on the results of the second glycemic control test. In some embodiments, the method includes discontinuing treatment of the individual with the first dose of the antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control by the second glycemic control test. In some embodiments, the method includes discontinuing treatment of the individual with the first dose of the antagonist of IGF1R signaling if the individual exhibits normal glycemic control by the second glycemic control test.

[0054] In some embodiments, the method includes a step 112 of administering a second dose of an antagonist of IGF1R signaling to the individual. In some embodiments, the method includes administering a second dose of an antagonist of IGF1R signaling to the individual based on the results of a second glycemic control test. In some embodiments, the method includes administering a second dose of an antagonist of IGF1R signaling to the individual if the individual exhibits abnormal glycemic control by the second glycemic control test. In some embodiments, the method includes administering a second dose of an antagonist of IGF1R signaling to the individual if the individual exhibits normal glycemic control by the second glycemic control test. In some embodiments, the second dose of the antagonist of IGF1R signaling is the same as the first dose of the antagonist of IGF1R signaling. In some embodiments, the second dose of the antagonist of IGF1R signaling is different from the first dose of the antagonist of IGF1R signaling. In some embodiments, the second dose of the antagonist of IGF1R signaling is higher than the first dose of the antagonist of IGF1R signaling. In some embodiments, the second dose of the antagonist of IGF1R signaling is lower than the first dose of the antagonist of IGF1R signaling. In some embodiments, the second blood glucose control test is a different test than the first blood glucose control test. In some embodiments, the second blood glucose control test is the same test as the first blood glucose control test. In some embodiments, the method includes a step 114 of treating abnormal blood glucose control in the individual if the individual exhibits abnormal blood glucose control by the second blood glucose control test. In some embodiments, the treatment of the abnormal blood glucose control includes any suitable treatment, including but not limited to insulin therapy.

[0055] In some embodiments, the method 100 disclosed herein or one or more steps or processes of the method 100 may be performed using a pharmaceutical composition comprising an antagonist of IGF1R signaling, as described below. In some embodiments, the pharmaceutical composition comprises an effective amount of an antagonist of IGF1R signaling. In some embodiments, the method comprises obtaining the results of a first glycemic control test from an individual with an IGF1R-related disorder. In some embodiments, the method comprises selecting an individual with an IGF1R-related disorder for treatment with a pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the method comprises selecting an individual with an IGF1R-related disorder for treatment with a pharmaceutical composition comprising an antagonist of IGF1R signaling based on the results of the first glycemic control test. In some embodiments, the method comprises selecting an individual with an IGF1R-related disorder for treatment with a pharmaceutical composition comprising an antagonist of IGF1R signaling if the individual with the IGF1R-related disorder exhibits normal glycemic control by the first glycemic control test. In some embodiments, the method comprises selecting an individual with an IGF1R-related disorder for treatment with a pharmaceutical composition comprising an antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control by the first glycemic control test. In some embodiments, the method comprises treating abnormal glycemic control in an individual with an IGF1R-related disorder prior to selecting the individual for treatment with a pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the treatment of abnormal glycemic control comprises any suitable treatment, including but not limited to insulin therapy.

[0056] In some embodiments, the method comprises administering to the individual a first dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the method comprises administering to the individual a first dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling based on the results of a first glycemic control test. In some embodiments, the method comprises administering to the individual a first dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling if the individual exhibits normal glycemic control by the first glycemic control test. In some embodiments, the method comprises administering to the individual a first dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control by the first glycemic control test. In some embodiments, the method comprises treating the individual's abnormal glycemic control prior to administering to the individual a first dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling.

[0057] In some embodiments, the method includes obtaining the results of a second glycemic control test from an individual treated with a first dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the method includes discontinuing treatment of the individual with the first dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the method includes discontinuing treatment of the individual with the first dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling based on the results of the second glycemic control test. In some embodiments, the method includes discontinuing treatment of the individual with the first dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control by the second glycemic control test. In some embodiments, the method includes discontinuing treatment of the individual with the first dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling if the individual exhibits normal glycemic control by the second glycemic control test.

[0058] In some embodiments, the method comprises administering to the individual a second dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the method comprises administering to the individual a second dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling based on the results of a second glycemic control test. In some embodiments, the method comprises administering to the individual a second dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control by the second glycemic control test. In some embodiments, the method comprises administering to the individual a second dose of a pharmaceutical composition comprising an antagonist of IGF1R signaling if the individual exhibits normal glycemic control by the second glycemic control test. In some embodiments, the second dose of the pharmaceutical composition comprising an antagonist of IGF1R signaling is the same as the first dose of the pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the second dose of the pharmaceutical composition comprising an antagonist of IGF1R signaling is different from the first dose of the pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the second dose of the pharmaceutical composition comprising an antagonist of IGF1R signaling is higher than the first dose of the pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the second dose of the pharmaceutical composition comprising an antagonist of IGF1R signaling is lower than the first dose of the pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the second glycemic control test is a different test from the first glycemic control test. In some embodiments, the second glycemic control test is the same test as the first glycemic control test. In some embodiments, the method includes treating abnormal glycemic control of the individual if the individual exhibits abnormal glycemic control by the second glycemic control test. In some embodiments, the treatment of the abnormal glycemic control includes any suitable treatment, including but not limited to insulin treatment.

[0059] In some embodiments, the IGF1R-related disorder comprises thyroid eye disease (TED). In some embodiments, the thyroid eye disease is Graves' ophthalmopathy, Graves' ophthalmopathy, Graves' orbitopathy, or thyroid-associated ophthalmopathy (TAO). In some embodiments, the antagonist of IGF1R signaling inhibits, reduces, blocks or prevents IGF1R signaling. In some embodiments, the antagonist of IGF1R signaling comprises an antibody that binds to IGF1R. In some embodiments, the binding of the antagonist of IGF1R signaling to IGF1R inhibits, reduces, blocks or prevents IGF1R signaling. In some embodiments, the antibody that binds to IGF1R comprises one or more selected from the group consisting of: ganituzumab, fentolumab, MEDI-573, situmumab, darototumumab, rotumumab, AVE1642, BIIB022, zhentuzumab, estuzumab, lincitinib, and tetuzumab. In some embodiments, the antibody that binds to IGF1R includes two selected from the group consisting of: ganituzumab, fentolumab, MEDI-573, citumumab, darotozumab, rotolumab, AVE1642, BIIB022, zhentuzumab, asiltuzumab, linsitinib, and tetulumab. In some embodiments, the antibody that binds to IGF1R includes three selected from the group consisting of: ganituzumab, fentolumab, MEDI-573, citumumab, darotozumab, rotolumab, AVE1642, BIIB022, zhentuzumab, asiltuzumab, linsitinib, and tetulumab. In some embodiments, the antibody that binds to IGF1R includes four or more selected from the group consisting of: ganituzumab, fentolumab, MEDI-573, citumumab, darotozumab, rotuximab, AVE1642, BIIB022, zhentuzumab, estuzumab, linsitinib, and tetutumumab. In some embodiments, the antibody that binds to IGF1R includes tetutumumab, also known as (Tetutumumab-trbw). In some embodiments, the antagonist of IGF1R signaling includes a small molecule that inhibits, reduces, blocks or prevents IGF1R signaling. In some embodiments, the small molecule includes one or more selected from the group consisting of picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, ganetespib, ceritinib and A-928605. In some embodiments, the small molecule comprises two selected from the group consisting of picropodophyllotoxin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, ganetespib, ceritinib, and A-928605. In some embodiments, the small molecule includes three selected from the group consisting of picropodophyllotoxin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, ganetespib, ceritinib, and A-928605.In some embodiments, the small molecule includes four or more selected from the group consisting of picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, ganetespib, ceritinib, and A-928605.

[0060] In some embodiments, the antagonist of IGF1R signaling comprises: (a) an antibody that binds to IGF1R; and (b) a small molecule that inhibits, reduces, blocks or prevents IGF1R signaling. In some embodiments, the antagonist of IGF1R signaling comprises (a) an antibody that binds to IGF1R, which comprises one or more selected from the group consisting of: ganituzumab, fentolumab, MEDI-573, citumumab, darotozumab, rotumumab, AVE1642, BIIB022, zhentuzumab, estuzumab, linsitinib, and tetumumab; and (b) a small molecule that inhibits, reduces, blocks or prevents IGF1R signaling, which comprises one or more selected from the group consisting of picropodophyllin, BMS-7548 07, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100(NDGA), XL-228, ganetespib, ceritinib, and A-928605. In some embodiments, the antagonist of IGF1R signaling comprises (a) an antibody that binds to IGF1R, including tetumumab; and (b) a small molecule that inhibits, reduces, blocks or prevents IGF1R signaling, including one or more selected from the group consisting of picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK190452 9A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100(NDGA), XL-228, ganetespib, ceritinib, and A-928605.

[0061] In some embodiments, the antibody that binds IGF1R comprises an amino acid sequence according to any one listed in Table 1.

[0062] Table 1. Sequences of Tetumumab

[0063]

[0064]

[0065] HC 1 : Heavy chain

[0066] LC 2 :Light chain

[0067] V H 3 : Heavy chain variable region

[0068] V L 4 : Light chain variable region

[0069] HCDR1 5 : First heavy chain complementarity determining region

[0070] HCDR2 6 : Second heavy chain complementarity determining region

[0071] HCDR3 7 : The third heavy chain complementarity determining region

[0072] LCDR1 8 : First light chain complementarity determining region

[0073] LCDR2 9 : Second light chain complementarity determining region

[0074] LCDR3 10 : The third light chain complementarity determining region

[0075] In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising a first heavy chain complementarity determining region (HCDR1) comprising an amino acid sequence according to SEQ ID No.: 5. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising a second heavy chain complementarity determining region (HCDR2) comprising an amino acid sequence according to SEQ ID No.: 6. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising a third heavy chain complementarity determining region (HCDR3) comprising an amino acid sequence according to SEQ ID No.: 7. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising: (a) a HCDR1 comprising an amino acid sequence according to SEQ ID No.: 5; (b) a HCDR2 comprising an amino acid sequence according to SEQ ID No.: 6; and (c) a HCDR3 comprising an amino acid sequence according to SEQ ID No.: 7. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising a first light chain complementary determining region (LCDR1) comprising an amino acid sequence according to SEQ ID No.: 8. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising a second light chain complementary determining region (LCDR2) comprising an amino acid sequence according to SEQ ID No.: 9. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising a third light chain complementary determining region (LCDR3) comprising an amino acid sequence according to SEQ ID No.: 10. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising: (a) LCDR1 comprising an amino acid sequence according to SEQ ID No.: 8; (b) LCDR2 comprising an amino acid sequence according to SEQ ID No.: 9; and (c) LCDR3 comprising an amino acid sequence according to SEQ ID No.: 10. In some embodiments, the antibody that binds to IGF1R comprises: (a) a heavy chain comprising: (i) HCDR1 comprising the amino acid sequence of SEQ ID No.:5; (ii) HCDR2 comprising the amino acid sequence of SEQ ID No.:6; and (iii) HCDR3 comprising the amino acid sequence of SEQ ID No.:7; and (b) a light chain comprising: (i) LCDR1 comprising the amino acid sequence of SEQ ID No.:8; (ii) LCDR2 comprising the amino acid sequence of SEQ ID No.:9; and (iii) LCDR3 comprising the amino acid sequence of SEQ ID No.:10.

[0076] In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 75% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 76% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 77% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 78% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 79% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 80% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 81% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 82% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 83% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 84% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 85% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H), the heavy chain variable domain comprising an amino acid sequence having at least 86% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 87% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 88% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 89% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 90% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 91% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 92% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 93% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 94% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 95% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 96% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H), the heavy chain variable domain comprising an amino acid sequence having at least 97% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 98% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 99% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprises the amino acid sequence according to SEQ ID No.: 3.

[0077] In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ), the light chain variable domain comprising an amino acid sequence having at least 75% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ), the light chain variable domain comprising an amino acid sequence having at least 76% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ), the light chain variable domain comprising an amino acid sequence having at least 77% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ), the light chain variable domain comprising an amino acid sequence having at least 78% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ), the light chain variable domain comprising an amino acid sequence having at least 79% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ), the light chain variable domain comprises an amino acid sequence having at least 80% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 81% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H), the heavy chain variable domain comprising an amino acid sequence having at least 82% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 83% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 84% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 85% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 86% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 87% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 88% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 89% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 90% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 91% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 92% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H), the heavy chain variable domain comprising an amino acid sequence having at least 93% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 94% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 95% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 96% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 97% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 98% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ), the heavy chain variable domain comprising an amino acid sequence having at least 99% sequence identity to SEQ ID No.: 3. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ), the light chain variable domain comprising the amino acid sequence according to SEQ ID No.:4.

[0078] In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 75% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 75% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 76% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 76% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H, the V H comprising an amino acid sequence having at least 77% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 77% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 78% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 78% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 79% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 79% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 80% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 80% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 81% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 81% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 82% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 82% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 83% sequence identity to SEQ ID No.: 3; and V L , the V Lcomprising an amino acid sequence having at least 83% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 84% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 84% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 85% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 85% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 86% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 86% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 87% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 87% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 88% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 88% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 89% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 89% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V Hcomprising an amino acid sequence having at least 90% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 90% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 91% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 91% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 92% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 92% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 93% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 93% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 94% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 94% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 95% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 95% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 96% sequence identity to SEQ ID No.: 3; and V L , the V Lcomprising an amino acid sequence having at least 96% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 97% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 97% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 98% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 98% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising an amino acid sequence having at least 99% sequence identity to SEQ ID No.: 3; and V L , the V L comprising an amino acid sequence having at least 99% sequence identity to SEQ ID No.: 4. In some embodiments, the antibody that binds to IGF1R comprises V H , the V H comprising the amino acid sequence according to SEQ ID No.: 3; and V L , the V L Comprising the amino acid sequence according to SEQ ID No.:4.

[0079] In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 75% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 76% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 77% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 78% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 79% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 80% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 81% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 82% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 83% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 84% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 85% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 86% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 87% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 88% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 89% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 90% sequence identity to SEQ ID No.: 1.In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 91% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 92% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 93% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 94% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 95% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 96% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 97% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 98% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 99% sequence identity to SEQ ID No.: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence according to SEQ ID No.: 1.

[0080] In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 75% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 76% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 77% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 78% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 79% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 80% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 81% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 82% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 83% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 84% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 85% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 86% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 87% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 88% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 89% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 90% sequence identity to SEQ ID No.: 2.In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 91% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 92% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 93% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 94% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 95% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 96% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 97% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 98% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 99% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence according to SEQ ID No.: 2.

[0081] In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 75% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 75% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 76% sequence identity to SEQ ID No.: 1 and a light chain comprising an amino acid sequence having at least 76% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 77% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 77% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 78% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 78% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 79% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 79% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 80% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 80% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 81% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 81% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 82% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 82% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 83% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 83% sequence identity to SEQ ID No.: 2.In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 84% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 84% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 85% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 85% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 86% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 86% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 87% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 87% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 88% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 88% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 89% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 89% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 90% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 90% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 91% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 91% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 92% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 92% sequence identity to SEQ ID No.: 2.In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 93% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 93% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 94% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 94% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 95% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 95% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 96% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 96% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 97% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 97% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 98% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 98% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 99% sequence identity to SEQ ID No.: 1; and a light chain comprising an amino acid sequence having at least 99% sequence identity to SEQ ID No.: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence according to SEQ ID No.: 1; and a light chain comprising an amino acid sequence according to SEQ ID No.: 2.

[0082] In some embodiments, the blood glucose control test includes a test for measuring the glucose level in a blood sample. In some embodiments, the blood glucose control test includes a test for measuring the sugar level in a blood sample. In some embodiments, when the blood glucose level is within a first range, the individual can be classified as healthy. In some embodiments, when the blood glucose level is within a second range and each value of the second range is higher than each value within the first range, the individual can be classified as having prediabetes. In some embodiments, when the blood glucose level is within a third range and each value of the third range is higher than each value within the second range, the individual can be classified as having diabetes. In some embodiments, the blood glucose control test includes any type of test that has been used, is being used, or will be used to measure blood glucose levels. In some embodiments, the blood glucose control test includes any type of test that has been used, is being used, or will be used to diagnose disorders related to blood glucose, including but not limited to high blood glucose levels, hyperglycemia, prediabetes, diabetes, type I diabetes, type II diabetes, gestational diabetes, impaired glucose tolerance, or glucose intolerance. In some embodiments, a blood glucose test kit, a blood glucose test device, or both can be used to perform a blood glucose control test. In some embodiments, the blood glucose control test includes the measurement of hemoglobin A1c (HbA1c), an oral glucose tolerance test, the measurement of fasting blood glucose, the measurement of non-fasting blood glucose, or any combination thereof. In some embodiments, a glycemic control test disclosed herein is suitable for use in a first glycemic control test of a method disclosed herein, a second glycemic control test of a method disclosed herein, or both.

[0083] In some embodiments, the glycemic control test comprises a measurement of hemoglobin A1c (HbA1c) in a blood sample. In some embodiments, the measurement of hemoglobin A1c (HbA1c) in a blood sample is also referred to as a glycated hemoglobin test, a glycosylated hemoglobin test, a hemoglobin A1C test, or an HbA1c test. In some embodiments, the HbA1c test comprises a measurement of glycated hemoglobin in a blood sample. In some embodiments, the HbA1c test comprises a measurement of an average level of glycated hemoglobin in a blood sample over a period of time. In some embodiments, the HbA1c test comprises a measurement of an average level of a percentage of glycated hemoglobin in the total amount of hemoglobin in a blood sample over a period of time. In some embodiments, the period of time is about 90 days. In some embodiments, the time period for the HbA1c test is between about 0 and about 24 months, for example, about 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, 11.0, 11.5, 12.0 , 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, 20.5, 21.0, 21.5, 22.0, 22.5, 23.0, 23.5 or about 24.0 months, or any time period therebetween. In some embodiments, the time period for the HbA1c test is between about 0 and about 24 months, between about 0 and about 12 months, between about 0 and about 6 months, between about 0 and about 5 months, between about 0 and about 4 months, between about 0 and about 3 months, between about 0 and about 2 months, between about 0 and about 1 month, between about 1 and 24 months, between about 1 and 12 months, between about 1 and 6 months, between about 1 and 5 months, between about 1 and 4 months, between about 1 and 3 months, between about 1 and 2 months, between about 2 and 24 In some embodiments, the HbA1c test is performed for a period of about 1 month. In some embodiments, the HbA1c test is performed for a period of about 2 months. In some embodiments, the HbA1c test is performed for a period of about 3 months.

[0084] In some embodiments, if the measurement of the HbA1c is less than about 4.5%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 4.6%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 4.7%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 4.8%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 4.9%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 5.0%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 5.1%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 5.2%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 5.3%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 5.4%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 5.5%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 5.6%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 5.7%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 5.8%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 5.9%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 6.0%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 6.1%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 6.2%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is below about 6.3%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is below about 6.4%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is below about 6.5%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is below about 6.6%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is below about 6.7%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is below about 6.8%, the individual exhibits normal glycemic control.In some embodiments, if the measurement of the HbA1c is less than about 6.9%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 7.0%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 7.1%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 7.2%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 7.3%, the individual exhibits normal glycemic control. %. In some embodiments, if the measurement of the HbA1c is less than about 7.4%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 7.5%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 7.6%, the individual exhibits normal glycemic control. In some embodiments, if the measurement of the HbA1c is less than about 7.7%, the individual exhibits normal glycemic control. In some embodiments, if the HbA1c measurement is below about 7.8%, the individual exhibits normal glycemic control. In some embodiments, if the HbA1c measurement is below about 7.9%, the individual exhibits normal glycemic control. In some embodiments, if the HbA1c measurement is below about 8.0%, the individual exhibits normal glycemic control. In some embodiments, if the HbA1c measurement is below about 8.5%, the individual exhibits normal glycemic control. In some embodiments, if the HbA1c measurement is below about 9.0%, the individual exhibits normal glycemic control.

[0085] In some embodiments, if the HbA1c measurement is between 0% and about 7.5%, for example, about 7.4%, about 7.3%, about 7.2%, about 7.1%, about 7%, about 6.9%, about 6.8%, about 6.7%, about 6.6%, about 6.5%, about 6.4%, about 6.3%, about 6.2%, about 6.1%, about 6%, about 5.9%, about 5.8%, about 5.7%, about 5.6%, about 5.5%, about 5.4%, about 5.3%, about 5.2%, about 5.1%, about 5%, about 4.9%, about 4.8%, about 4.7%, about 4.6%, about 4.5%, about 4.4%, about 4.3%, about 4.2%, about 4.1%, about 4.9%, about 4.8 ... If the subject's glycemic control is about 1%, about 2%, about 8%, about 3.7%, about 3.6%, about 3.5%, about 3.4%, about 3.3%, about 3.2%, about 3.1%, about 3%, about 2.9%, about 2.8%, about 2.7%, about 2.6%, about 2.5%, about 2.4%, about 2.3%, about 2.2%, about 2.1%, about 2%, about 1.9%, about 1.8%, about 1.7%, about 1.6%, about 1.5%, about 1.4%, about 1.3%, about 1.2%, about 1.1%, about 1%, about 0.9%, about 0.8%, about 0.7%, about 0.6%, about 0.5%, about 0.4%, about 0.3%, about 0.2%, or about 0.1%, or any percentage therebetween, the subject exhibits normal glycemic control.

[0086] In some embodiments, the method of treating an individual with an IGF1R-associated disorder includes the step of not selecting the individual for treatment with an antagonist of IGF1R signaling if the individual with the IGF1R-associated disorder exhibits abnormal glycemic control. In some embodiments, the individual exhibits abnormal glycemic control if the measurement of the HbA1c is at least about 4.5%. In some embodiments, the individual exhibits abnormal glycemic control if the measurement of the HbA1c is at least about 4.6%. In some embodiments, the individual exhibits abnormal glycemic control if the measurement of the HbA1c is at least about 4.7%. In some embodiments, the individual exhibits abnormal glycemic control if the measurement of the HbA1c is at least about 4.8%. In some embodiments, the individual exhibits abnormal glycemic control if the measurement of the HbA1c is at least about 4.9%. In some embodiments, the individual exhibits abnormal glycemic control if the measurement of the HbA1c is at least about 5.0%. In some embodiments, the individual exhibits abnormal glycemic control if the measurement of the HbA1c is at least about 5.1%. In some embodiments, if the measurement of the HbA1c is at least about 5.2%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 5.3%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 5.4%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 5.5%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 5.6%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 5.7%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 5.8%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 5.9%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 6.0%, the individual exhibits abnormal glycemic control. In some embodiments, the individual exhibits abnormal glycemic control if the HbA1c is measured at least about 6.1%. In some embodiments, the individual exhibits abnormal glycemic control if the HbA1c is measured at least about 6.2%. In some embodiments, the individual exhibits abnormal glycemic control if the HbA1c is measured at least about 6.3%. In some embodiments, the individual exhibits abnormal glycemic control if the HbA1c is measured at least about 6.4%. In some embodiments, the individual exhibits abnormal glycemic control if the HbA1c is measured at least about 6.5%. In some embodiments, the individual exhibits abnormal glycemic control if the HbA1c is measured at least about 6.In some embodiments, if the measurement of HbA1c is at least about 6.6%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of HbA1c is at least about 6.7%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of HbA1c is at least about 6.8%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of HbA1c is at least about 6.9%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of HbA1c is at least about 7.0%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of HbA1c is at least about 7.1%, the individual exhibits abnormal glycemic control. %. In some embodiments, if the measurement of HbA1c is at least about 7.2%, the individual exhibits abnormal glycemic control. %. In some embodiments, if the measurement of HbA1c is at least about 7.3%, the individual exhibits abnormal glycemic control. %. In some embodiments, if the measurement of HbA1c is at least about 7.4%, the individual exhibits abnormal glycemic control. %. In some embodiments, if the measurement of the HbA1c is at least about 7.5%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 7.6%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 7.7%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 7.8%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 7.9%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 8.0%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 8.5%, the individual exhibits abnormal glycemic control. In some embodiments, if the measurement of the HbA1c is at least about 9.0%, the individual exhibits abnormal glycemic control. In some embodiments, if the HbA1c is measured to be at least about 4.5%, for example about 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5%, 5.1%, 5.2%, 5.3%, 5.4%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9%, 6%, 6.1%, 6.2%, 6.3%, 6.4%, 6.5%, 6.6%, 6.7%, 6.8%, 6.9%, 7%, 7.1%, 7.2%, 7.3%, 7.4%, 7.5%, 7.6%, 7.7%, 7.8%, 7.9%, 8.1%, 8.2%, 8.3%, 8.4%, 8.5%, 8.6%, 8.7%, 8.8%, 8.9%, 9.In some embodiments, the test for glycemic control includes an oral glucose tolerance test. In some embodiments, the oral glucose tolerance test includes the measurement of the response of an individual to glucose. In some embodiments, the oral glucose tolerance test includes subjecting an individual to fasting for a period of time. In some embodiments, the fasting period is overnight. In some embodiments, the fasting period is about 6 hours to about 18 hours, such as about 6 hours, 6.5 hours, 7 hours, 7.5 hours, 8 hours, 8.5 hours, 9 hours, 9.5 hours, 10 hours, 10.5 hours, 11 hours, 11.5 hours, 12 hours, 12.5 hours, 13 hours, 13.5 hours, 14 hours, 14.5 hours, 15 hours, 15.5 hours, 16 hours, 16.5 hours, 17 hours, 17.5 hours, or 18 hours or any duration therebetween. In some embodiments, the fasting period is from about 6 hours to about 18 hours, from about 6 hours to about 17.5 hours, from about 6 hours to about 17 hours, from about 6 hours to about 16.5 hours, from about 6 hours to about 16 hours, from about 6 hours to about 15.5 hours, from about 6 hours to about 15 hours, from about 6 hours to about 14.5 hours, from about 6 hours to about 14 hours, from about 6 hours to about 13.5 hours, from about 6 hours to about 13 hours, from about 6 hours to about 12.5 hours, from about 6 hours to about 12 hours. hours, about 6 hours to about 11.5 hours, about 6 hours to about 11 hours, about 6 hours to about 10.5 hours, about 6 hours to about 10 hours, about 6 hours to about 9.5 hours, about 6 hours to about 9 hours, about 6 hours to about 8.5 hours, about 6 hours to about 8 hours, about 6 hours to about 7.5 hours, about 6 hours to about 7 hours, about 6 hours to about 6.5 hours, about 7 hours to about 18 hours, about 7 hours to about 17.5 hours, about 7 hours to about 17 hours, about 7 hours to about 16.5 hours, about 7 hours to about 16 hours, about 7 hours to about 15.5 hours, about 7 hours to about 15 hours, about 7 hours to about 14.5 hours, about 7 hours to about 14 hours, about 7 hours to about 13.5 hours, about 7 hours to about 13 hours, about 7 hours to about 12.5 hours, about 7 hours to about 12 hours, about 7 hours to about 11.5 hours, about 7 hours to about 11 hours, about 7 hours to about 10.5 hours, about 7 hours to about 10 hours, about 7 hours to about 9.5 hours, about 7 hours to about 9 hours, about 7 hours to about 8.5 hours, about 7 hours to about 8 hours, about 7 hours to about 7.5 hours, about 8 hours to about 18 hours, about 8 hours to about 17.5 hours, about 8 hours to about 17 hours, about 8 hours to about 16.5 hours, about 8 hours to about 16 hours, about 8 hours to about 15.5 hours, about 8 hours to about 15 hours, about 8 hours to about 14.5 hours, about 8 hours to about 14 hours, about 8 hours to about 13.5 hours, about 8 hours to about 13 hours, about 8 hours to about 12.5 hours, about 8 hours to about 12 hours, about 8 hours to about 11.5 hours, about 8 hours to about 11 hours, about 8 hours to about 10.5 hours, about 8 hours to about 10 hours, about 8 hours to about 9.5 hours, about 8 hours to about 9 hours, about 8 hours to about 8.5 hours, about 9 hours to about 18 hours, about 9 hours to about 17.5 hours, about 9 hours to about 17 hours, about 9 hours to about 16.5 hours, about 9 hours to about 16 hours, about 9 hours to about 15.5 hours, about 9 hours to about 15 hours, about 9 hours to about 14.5 hours, about 9 hours to about 14 hours, about 9 hours to about 13.5 hours, about 9 hours 14 hours, about 15 hours to about 16 hours, about 17 hours to about 18 hours, about 19 hours to about 19 hours, about 20 hours to about 18 hours, about 15 ... , about 10 hours to about 12 hours, about 10 hours to about 11.5 hours, about 10 hours to about 11 hours, about 10 hours to about 10.5 hours, about 11 hours to about 18 hours, about 11 hours to about 17.5 hours, about 11 hours to about 17 hours, about 11 hours to about 16.5 hours, about 11 hours to about 16 hours, about 11 hours to about 15.5 hours, about 11 hours to about 15 hours, about 11 hours to about 14.5 hours, about 11 hours to about 14 hours, about 11 hours to about 13.5 hours, about 11 hours to about 13 hours, about 11 hours to about 12.5 hours, about 11 hours to about 12 hours, about 11 hours to about 11.5 hours, about 12 hours to about 18 hours , about 12 hours to about 17.5 hours, about 12 hours to about 17 hours, about 12 hours to about 16.5 hours, about 12 hours to about 16 hours, about 12 hours to about 15.5 hours, about 12 hours to about 15 hours, about 12 hours to about 14.5 hours, about 12 hours to about 14 hours, about 12 hours to about 13.5 hours, about 12 hours to about 13 hours, about 12 hours to about 12.5 hours, about 13 hours to about 18 hours, about 13 hours to about 17.5 hours, about 13 hours to about 17 hours, about 13 hours to about 16.5 hours, about 13 hours to about 16 hours, about 13 hours to about 15.5 hours, about 13 hours to about 1 ...5 hours, about 13 hours to about 14 hours, about 13 hours to about 13.5 hours, about 14 hours to about 18 hours, about 14 hours to about 17.5 hours, about 14 hours to about 17 hours, about 14 hours to about 16.5 hours, about 14 hours to about 16 hours, about 14 hours to about 15.5 hours, about 14 hours to about 15 hours, about 14 hours to about 14.5 hours, about 15 hours to about 18 hours, about 15 hours to about 17.5 hours, about 15 hours to about 17 hours, about 15 hours to about 16.5 hours, about 15 hours to about 16 hours, about 15 hours to about 15.5 hours, about 16 hours to about 18 hours, about 16 hours to about 17.5 hours, about 16 hours to about 17 hours, about 16 hours to about 16.5 hours, about 17 hours to about 18 hours, or about 17 hours to about 17.5 hours. .

[0087] In some embodiments, the oral glucose tolerance test includes measuring a first blood glucose level of the individual after fasting. In some embodiments, the oral glucose tolerance test includes oral intake of a certain amount of sugar by the individual after fasting. In some embodiments, the oral glucose tolerance test includes oral intake of a certain amount of sugar by the individual after measuring the first blood glucose level of the individual. In some embodiments, the oral glucose tolerance test includes oral intake of a certain amount of glucose by the individual after fasting. In some embodiments, the oral glucose tolerance test includes oral intake of a certain amount of glucose by the individual after measuring the first blood glucose level of the individual. In some embodiments, the amount of sugar or glucose ingested is between about 50 and 150 grams (g), for example, about 50g, 51g, 52g, 53g, 54g, 55g, 56g, 57g, 58g, 59g, 60g, 61g, 62g, 63g, 64g, 65g, 66g, 67g, 68g, 69g, 70g, 71g, 72g, 73g, 74g, 75g, 76g, 77g, 78g, 79g, 80g, 81g, 82g, 83g, 84g, 85g, 86g, 87g, 88g, 89g, 90g, 91g, 92g, 93g, 94g, 95g, 96g, 97g, 98g, 99g, 100g, 101g, 102g , 103g, 104g, 105g, 106g, 107g, 108g, 109g, 110g, 111g, 112g, 113g, 114g, 11 5g, 116g, 117g, 118g, 119g, 120g, 121g, 122g, 123g, 124g, 125g, 126g, 127g, In some embodiments, the oral glucose tolerance test comprises an individual taking about 75g of sugar dissolved in an aqueous medium after fasting. In some embodiments, the oral glucose tolerance test comprises an individual taking about 75g of sugar dissolved in an aqueous medium after fasting. In some embodiments, the oral glucose tolerance test comprises an individual taking about 75g of sugar dissolved in an aqueous medium after fasting. In some embodiments, the oral glucose tolerance test comprises an individual taking about 75g of sugar dissolved in an aqueous medium after fasting. In some embodiments, the oral glucose tolerance test comprises an individual taking about 75g of sugar dissolved in an aqueous medium after measuring the first blood glucose level of the individual. In some embodiments, the oral glucose tolerance test comprises the individual orally ingesting about 75 g of glucose dissolved in an aqueous medium after measuring the individual's first blood glucose level. In some embodiments, the aqueous medium comprises water.

[0088] In certain embodiments, the oral glucose tolerance test is included in the second blood glucose level of the individual after the individual oral intake of sugar or glucose is measured. In certain embodiments, the duration between the individual oral intake of sugar or glucose and the second blood glucose level of the individual is about 30 minutes (min) to about 6 hours, such as about 30min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, or about 6 hours or any duration therebetween. In certain embodiments, the duration between the individual oral intake of about 75g of sugar or glucose dissolved in an aqueous medium and the second blood glucose level of the individual is about 30 minutes (min) to about 6 hours, such as about 30min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, or about 6 hours or any duration therebetween. In some embodiments, the duration between oral ingestion of a sugar or glucose dissolved in an aqueous medium by a subject and measurement of a second blood glucose level of the subject is about 30 min to about 6 hours, about 30 min to about 5.5 hours, about 30 min to about 5 hours, about 30 min to about 4.5 hours, about 30 min to about 4 hours, about 30 min to about 3.5 hours, about 30 min to about 3 hours, about 30 min to about 2.5 hours, about 30 min to about 2 hours, about 30 min to about 1.5 hours, about 30 min to about 1 hour, about 1 hour to about 6 hours, about 1 hour to about 5.5 hours, about 1 hour to about 5 hours, about 1 hour to about 4.5 hours, about 1 hour to about 4 hours, about 1 hour to about 3.5 hours, about 30 min to about 3 hours, about 30 min to about 2.5 hours, about 30 min to about 2 hours, about 30 min to about 1.5 hours, about 30 min to about 1 hour, about 1 hour to about 6 hours, about 1 hour to about 5.5 hours, about 1 hour to about 5 hours, about 1 hour to about 4.5 hours, about 1 hour to about 4 hours, about 1 hour to about 3.5 hours, about 1 hour to about 3 hours, about 1 hour to about 2.5 hours, about 1 hour to about 2 hours, 1.5 hours, about 2 hours to about 6 hours, about 2 hours to about 5.5 hours, about 2 hours to about 5 hours, about 2 hours to about 4.5 hours, about 2 hours to about 4 hours, about 2 hours to about 3.5 hours, about 2 hours to about 3 hours, about 2 hours to about 2.5 hours, about 2.5 hours to about 6 hours, about 2.5 hours to about 5.5 hours, about 2.5 hours to about 5 hours, about 2.5 hours to about 4.5 hours, about 2.5 hours to about 4 hours, about 2.5 hours to about 3.5 hours, about 2.5 hours to about 3 hours, about 3 hours to about 6 hours, about 3 hours to about 5.5 hours, about 3 hours to about 5 hours, about 3 hours to about 4.5 hours, about 3 hours to about 4 hours, about 3 hours to about 3.5 hours, about 4 hours to about 6 hours, about 4 hours to about 5.5 hours, about 4 hours to about 5 hours, or about 4 hours to about 4.5 hours.In some embodiments, the duration between the individual's oral ingestion of 75 g of sugar or glucose dissolved in an aqueous medium and the measurement of the individual's second blood glucose level is about 30 min to about 6 hours, about 30 min to about 5.5 hours, about 30 min to about 5 hours, about 30 min to about 4.5 hours, about 30 min to about 4 hours, about 30 min to about 3.5 hours, about 30 min to about 3 hours, about 30 min to about 2.5 hours, about 30 min to about 2 hours, about 30 min to about 1.5 hours, about 30 min to about 1 hour, about 1 hour to about 6 hours, about 1 hour to about 6 hours. to about 5.5 hours, about 1 hour to about 5 hours, about 1 hour to about 4.5 hours, about 1 hour to about 4 hours, about 1 hour to about 3.5 hours, about 1 hour to about 3 hours, about 1 hour to about 2.5 hours, about 1 hour to about 2 hours, about 1 hour to about 1.5 hours, about 1.5 hours to about 6 hours, about 1.5 hours to about 5.5 hours, about 1.5 hours to about 5 hours, about 1.5 hours to about 4.5 hours, about 1.5 hours to about 4 hours, about 1.5 hours to about 3.5 hours, about 1.5 hours to about 3 hours, about 1.5 hours to about 2.5 hours, about 1.5 hours to about 2 hours, about 2 hours to about 6 hours, about 2 hours to about 5.5 hours, about 2 hours to about 5 hours, about 2 hours to about 4.5 hours, about 2 hours to about 4 hours, about 2 hours to about 3.5 hours, about 2 hours to about 3 hours, about 2 hours to about 2.5 hours, about 2.5 hours to about 6 hours, about 2.5 hours to about 5.5 hours, about 2.5 hours to about 5 hours, about 2.5 hours to about 4.5 hours, about 2.5 hours to about 4 hours, about 2.5 hours to about 3.5 hours, about 2.5 hours to about 3 hours, about 3 hours to about 6 hours, about 3 hours to about 5.5 hours, about 3 hours From about 3 hours to about 4.5 hours, from about 3 hours to about 4 hours, from about 3 hours to about 3.5 hours, from about 3.5 hours to about 6 hours, from about 3.5 hours to about 5.5 hours, from about 3.5 hours to about 5 hours, from about 3.5 hours to about 4.5 hours, from about 3.5 hours to about 4 hours, from about 4 hours to about 6 hours, from about 4 hours to about 5.5 hours, from about 4 hours to about 5 hours, from about 4 hours to about 4.5 hours, from about 4.5 hours to about 6 hours, from about 4.5 hours to about 5.5 hours, from about 4.5 hours to about 5 hours, from about 5 hours to about 6 hours, or from about 5.5 hours to about 6 hours.

[0089] In some embodiments, the duration between an individual's oral intake of 75 g of sugar or glucose dissolved in an aqueous medium and the measurement of the individual's second blood glucose level is about 1 hour. In some embodiments, the duration between an individual's oral intake of about 75 g of sugar or glucose dissolved in an aqueous medium and the measurement of the individual's second blood glucose level is about 1.5 hours. In some embodiments, the duration between an individual's oral intake of about 75 g of sugar or glucose dissolved in an aqueous medium and the measurement of the individual's second blood glucose level is about 2 hours. In some embodiments, the duration between an individual's oral intake of about 75 g of sugar or glucose dissolved in an aqueous medium and the measurement of the individual's second blood glucose level is about 2.5 hours. In some embodiments, the duration between an individual's oral intake of about 75 g of sugar or glucose dissolved in an aqueous medium and the measurement of the individual's second blood glucose level is about 3 hours. In some embodiments, the duration between an individual's oral intake of about 75 g of sugar or glucose dissolved in an aqueous medium and the measurement of the individual's second blood glucose level is about 3.5 hours. In some embodiments, the duration between an individual's oral intake of about 75 g of sugar or glucose dissolved in an aqueous medium and the measurement of the individual's second blood glucose level is about 4 hours.

[0090] In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 250 milligrams per deciliter (mg / dL), the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 245 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 240 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 235 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 230 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 225 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 220 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 215 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 210 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 205 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 200 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 195 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 190 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 185 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 180 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 175 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 170 mg / dL, the individual exhibits normal blood glucose control.In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 165 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 160 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 155 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 150 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 145 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 140 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 135 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 130 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 125 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 120 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 115 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 110 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 105 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test does not exceed 100 mg / dL, the individual exhibits normal blood glucose control.

[0091] In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 250 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 245 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 240 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 235 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 230 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 225 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 220 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 215 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, the individual exhibits normal glycemic control if the individual's second blood glucose level as measured by an oral glucose tolerance test does not exceed 210 mg / dL and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium.In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 205 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 200 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 195 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 190 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 185 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 180 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 175 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 170 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, the individual exhibits normal glycemic control if the individual's second blood glucose level as measured by an oral glucose tolerance test does not exceed 165 mg / dL and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium.In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 160 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 155 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 150 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 145 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 140 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 135 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 130 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 125 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, the individual exhibits normal glycemic control if the individual's second blood glucose level as measured by an oral glucose tolerance test does not exceed 120 mg / dL and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium.In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 115 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 110 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 105 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test does not exceed 100 mg / dL, and the second blood glucose level is measured about 2 hours after the individual orally ingests about 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits normal blood glucose control.

[0092] In some embodiments, if the second blood glucose level of the individual as measured by an oral glucose tolerance test is from about 0 to about 250 mg / dL, for example, about 1 mg / dL, 2 mg / dL, 3 mg / dL, 4 mg / dL, 5 mg / dL, 6 mg / dL, 7 mg / dL, 8 mg / dL, 9 mg / dL, 10 mg / dL, 11 mg / dL, 12 mg / dL, 13 mg / dL, 14 mg / dL, 15 mg / dL, 16 mg / dL, 17 mg / dL, 18 mg / dL, 19 mg / dL, 20 mg / dL, 21 mg / dL, 22 mg / dL, 23 mg / dL, 24 mg / dL, 25 mg / dL, 26 mg / dL , 27mg / dL, 28mg / dL, 29mg / dL, 30mg / dL, 31mg / dL, 32mg / dL, 33mg / dL, 34mg / dL, 35mg / dL, 36mg / dL, 37mg / dL, 38mg / dL, 39mg / dL, 40mg / dL, 41mg / dL, 42m g / dL, 43mg / dL, 44mg / dL, 45mg / dL, 46mg / dL, 47mg / dL, 48mg / dL, 49mg / dL, 50mg / dL, 51mg / dL, 52mg / dL, 53mg / dL, 54mg / dL, 55mg / dL, 56mg / dL, 57mg / dL, 58mg / dL, 59mg / dL, 60mg / dL, 61mg / dL, 62mg / dL, 63mg / dL, 64mg / dL, 65mg / dL, 66mg / dL, 67mg / dL, 68mg / dL, 69mg / dL, 70mg / dL, 71mg / dL, 72mg / dL, 73mg / dL, 74mg / dL, 75mg / dL, 76mg / dL, 77mg / dL, 78mg / dL, 79mg / dL, 80mg / dL, 81mg / dL, 82mg / dL, 83mg / dL, 84mg / dL, 85mg / dL, 86mg / dL, 87mg / dL, 88mg / dL, 8 9mg / dL、90mg / dL、91mg / dL、92mg / dL、93mg / dL、94mg / dL、95mg / dL、96mg / dL、97mg / dL、98mg / dL、99mg / dL、100mg / dL、101mg / dL、102mg / dL、103mg / dL、1 04mg / dL, 105mg / dL, 106mg / dL, 107mg / dL, 108mg / dL, 109mg / dL, 110mg / dL, 111mg / dL, 112mg / dL, 113mg / dL, 114mg / dL, 115mg / dL, 116mg / dL, 117mg / dL,118mg / dL、119mg / dL、120mg / dL、121mg / dL、122mg / dL、123mg / dL、124mg / dL、125mg / dL、126mg / dL、127mg / dL、128mg / dL、129mg / dL、130mg / dL、131mg / dL、132mg / dL、133mg / dL、134mg / dL、135mg / dL、136mg / dL、137mg / dL、138mg / dL、139mg / dL、140mg / dL、141mg / dL、142mg / dL、143mg / dL、144mg / dL、145mg / dL、146mg / dL、147mg / dL、148mg / dL、149mg / dL、150mg / dL、151mg / dL、152mg / dL、153mg / dL、154mg / dL、155mg / dL、156mg / dL、157mg / dL、158mg / dL、159mg / dL、160mg / dL、161mg / dL、162mg / dL、163mg / dL、164mg / dL、165mg / dL、166mg / dL、167mg / dL、168mg / dL、169mg / dL、170mg / dL、171mg / dL、172mg / dL、173mg / dL、174mg / dL、175mg / dL、176mg / dL、177mg / dL、178mg / dL、179mg / dL、180mg / dL、181mg / dL、182mg / dL、183mg / dL、184mg / dL、185mg / dL、186mg / dL、187mg / dL、188mg / dL、189mg / dL、190mg / dL、191mg / dL、192mg / dL、193mg / dL、194mg / dL、195mg / dL、196mg / dL、197mg / dL、198mg / dL、199mg / dL、200mg / dL、201mg / dL、202mg / dL、203mg / dL、204mg / dL、205mg / dL、206mg / dL、207mg / dL、208mg / dL、209mg / dL、210mg / dL、211mg / dL、212mg / dL、213mg / dL、214mg / dL、215mg / dL、216mg / dL、217mg / dL、218mg / dL、219mg / dL、220mg / dL、221mg / dL、222mg / dL、223mg / dL、224mg / dL、225mg / dL、226mg / dL、227mg / dL、228mg / dL、If the individual has normal glycemic control, the individual exhibits normal glycemic control if the individual has a glycemic index of 229 mg / dL, 230 mg / dL, 231 mg / dL, 232 mg / dL, 233 mg / dL, 234 mg / dL, 235 mg / dL, 236 mg / dL, 237 mg / dL, 238 mg / dL, 239 mg / dL, 240 mg / dL, 241 mg / dL, 242 mg / dL, 243 mg / dL, 244 mg / dL, 245 mg / dL, 246 mg / dL, 247 mg / dL, 248 mg / dL, 249 mg / dL, or 250 mg / dL, or any concentration therebetween.

[0093] In some embodiments, during an oral glucose tolerance test, when the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or a sugar dissolved in an aqueous medium, if the second blood glucose level is between about 0 and about 250 mg / dL, e.g., about 1 mg / dL, 2 mg / dL, 3 mg / dL, 4 mg / dL, 5 mg / dL, 6 mg / dL, 7 mg / dL, 8 mg / dL, 9 mg / dL, 10 mg / dL, 11 mg / dL, 12 mg / dL, 13 mg / dL, 14 mg / dL, 15 mg / dL, 16 mg / dL, 17 mg / dL, 18 mg / dL, 19 mg / dL, 20 mg / dL, 21 mg / dL, 22 mg / dL, 2mg / dL, 23mg / dL, 24mg / dL, 25mg / dL, 26mg / dL, 27mg / dL, 28mg / dL, 29mg / dL, 30mg / dL, 31mg / dL, 32mg / dL, 33mg / dL, 34mg / dL, 35mg / dL, 36mg / dL, 37mg / d L, 38mg / dL, 39mg / dL, 40mg / dL, 41mg / dL, 42mg / dL, 43mg / dL, 44mg / dL, 45mg / dL, 46mg / dL, 47mg / dL, 48mg / dL, 49mg / dL, 50mg / dL, 51mg / dL, 52mg / dL, 53m g / dL, 54mg / dL, 55mg / dL, 56mg / dL, 57mg / dL, 58mg / dL, 59mg / dL, 60mg / dL, 61mg / dL, 62mg / dL, 63mg / dL, 64mg / dL, 65mg / dL, 66mg / dL, 67mg / dL, 68mg / dL , 69mg / dL, 70mg / dL, 71mg / dL, 72mg / dL, 73mg / dL, 74mg / dL, 75mg / dL, 76mg / dL, 77mg / dL, 78mg / dL, 79mg / dL, 80mg / dL, 81mg / dL, 82mg / dL, 83mg / dL, 84mg 1 00mg / dL, 101mg / dL, 102mg / dL, 103mg / dL, 104mg / dL, 105mg / dL, 106mg / dL, 107mg / dL, 108mg / dL, 109mg / dL, 110mg / dL, 111mg / dL, 112mg / dL, 113mg / dL,114mg / dL、115mg / dL、116mg / dL、117mg / dL、118mg / dL、119mg / dL、120mg / dL、121mg / dL、122mg / dL、123mg / dL、124mg / dL、125mg / dL、126mg / dL、127mg / dL、128mg / dL、129mg / dL、130mg / dL、131mg / dL、132mg / dL、133mg / dL、134mg / dL、135mg / dL、136mg / dL、137mg / dL、138mg / dL、139mg / dL、140mg / dL、141mg / dL、142mg / dL、143mg / dL、144mg / dL、145mg / dL、146mg / dL、147mg / dL、148mg / dL、149mg / dL、150mg / dL、151mg / dL、152mg / dL、153mg / dL、154mg / dL、155mg / dL、156mg / dL、157mg / dL、158mg / dL、159mg / dL、160mg / dL、161mg / dL、162mg / dL、163mg / dL、164mg / dL、165mg / dL、166mg / dL、167mg / dL、168mg / dL、169mg / dL、170mg / dL、171mg / dL、172mg / dL、173mg / dL、174mg / dL、175mg / dL、176mg / dL、177mg / dL、178mg / dL、179mg / dL、180mg / dL、181mg / dL、182mg / dL、183mg / dL、184mg / dL、185mg / dL、186mg / dL、187mg / dL、188mg / dL、189mg / dL、190mg / dL、191mg / dL、192mg / dL、193mg / dL、194mg / dL、195mg / dL、196mg / dL、197mg / dL、198mg / dL、199mg / dL、200mg / dL、201mg / dL、202mg / dL、203mg / dL、204mg / dL、205mg / dL、206mg / dL、207mg / dL、208mg / dL、209mg / dL、210mg / dL、211mg / dL、212mg / dL、213mg / dL、214mg / dL、215mg / dL、216mg / dL、217mg / dL、218mg / dL、219mg / dL、220mg / dL、221mg / dL、222mg / dL、223mg / dL、224mg / dL、dL, 225 mg / dL, 226 mg / dL, 227 mg / dL, 228 mg / dL, 229 mg / dL, 230 mg / dL, 231 mg / dL, 232 mg / dL, 233 mg / dL, 234 mg / dL, 235 mg / dL, 236 mg / dL, 237 mg / dL, 238 mg / dL, 239 mg / dL, 240 mg / dL, 241 mg / dL, 242 mg / dL, 243 mg / dL, 244 mg / dL, 245 mg / dL, 246 mg / dL, 247 mg / dL, 248 mg / dL, 249 mg / dL, or 250 mg / dL, or any concentration therebetween, then the individual exhibits normal glycemic control.

[0094] In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 250 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 240 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 230 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 220 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 210 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 200 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 190 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 180 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 170 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 160 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 150 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 140 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 130 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual measured by the oral glucose tolerance test is higher than 120 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the second blood glucose level of the individual as measured by an oral glucose tolerance test is above 110 mg / dL, the individual exhibits abnormal glycemic control. In some embodiments, if the second blood glucose level of the individual as measured by an oral glucose tolerance test is above 100 mg / dL, the individual exhibits abnormal glycemic control.

[0095] In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 250 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 240 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 230 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 220 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 210 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 200 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 190 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 180 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, the individual exhibits abnormal glycemic control if the second blood glucose level of the individual as measured by an oral glucose tolerance test is above 170 mg / dL and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or a sugar dissolved in an aqueous medium. In some embodiments, the individual exhibits abnormal glycemic control if the second blood glucose level of the individual as measured by an oral glucose tolerance test is above 160 mg / dL and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or a sugar dissolved in an aqueous medium.In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 150 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 140 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 130 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, if the second blood glucose level of the individual measured by an oral glucose tolerance test is higher than 120 mg / dL, and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or sugar dissolved in an aqueous medium, the individual exhibits abnormal glycemic control. In some embodiments, the individual exhibits abnormal glycemic control if the second blood glucose level of the individual as measured by an oral glucose tolerance test is above 110 mg / dL and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or a sugar dissolved in an aqueous medium. In some embodiments, the individual exhibits abnormal glycemic control if the second blood glucose level of the individual as measured by an oral glucose tolerance test is above 100 mg / dL and the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or a sugar dissolved in an aqueous medium.

[0096] In some embodiments, if the second blood glucose level of the individual as measured by an oral glucose tolerance test is above about 100 mg / dL, such as about 101 mg / dL, 102 mg / dL, 103 mg / dL, 104 mg / dL, 105 mg / dL, 106 mg / dL, 107 mg / dL, 108 mg / dL, 109 mg / dL, 110 mg / dL, 111 mg / dL, 112 mg / dL, 113 mg / dL, 114 mg / dL, 115 mg / dL, 116 mg / dL, 117 mg / dL, 118 mg / dL, 119 mg / dL, 120 mg / dL, 121 mg / dL, 122 mg / dL, 123 mg / dL, 124 mg / dL, 125 3mg / dL, 124mg / dL, 125mg / dL, 126mg / dL, 127mg / dL, 128mg / dL, 129mg / dL, 130mg / dL, 131mg / dL, 132mg / dL, 133mg / dL, 134mg / dL, 135mg / dL, 136mg / dL, 137mg / dL, 138mg / dL, 139mg / dL, 140mg / dL, 141mg / dL, 142mg / dL, 143mg / dL, 144mg / dL, 145mg / dL, 146mg / dL, 147mg / dL, 148mg / dL, 149mg / dL, 150mg / d L, 151mg / dL, 152mg / dL, 153mg / dL, 154mg / dL, 155mg / dL, 156mg / dL, 157mg / dL, 158mg / dL, 159mg / dL, 160mg / dL, 161mg / dL, 162mg / dL, 163mg / dL, 164mg / dL, 165mg / dL, 166mg / dL, 167mg / dL, 168mg / dL, 169mg / dL, 170mg / dL, 171mg / dL, 172mg / dL, 173mg / dL, 174mg / dL, 175mg / dL, 176mg / dL, 177mg / dL, 178 mg / dL, 179mg / dL, 180mg / dL, 181mg / dL, 182mg / dL, 183mg / dL, 184mg / dL, 185mg / dL, 186mg / dL, 187mg / dL, 188mg / dL, 189mg / dL, 190mg / dL, 191mg / dL, 1 92mg / dL, 193mg / dL, 194mg / dL, 195mg / dL, 196mg / dL, 197mg / dL, 198mg / dL, 199mg / dL, 200mg / dL, 201mg / dL, 202mg / dL, 203mg / dL, 204mg / dL, 205mg / dL,206mg / dL, 207mg / dL, 208mg / dL, 209mg / dL, 210mg / dL, 211mg / dL, 212mg / dL, 213mg / dL, 214mg / dL, 2 15mg / dL, 216mg / dL, 217mg / dL, 218mg / dL, 219mg / dL, 220mg / dL, 221mg / dL, 222mg / dL, 223mg / dL, 224 mg / dL, 225mg / dL, 226mg / dL, 227mg / dL, 228mg / dL, 229mg / dL, 230mg / dL, 231mg / dL, 232mg / dL, 233mg / dL, 234mg / dL, 235mg / dL, 236mg / dL, 237mg / dL, 238mg / dL, 239mg / dL, 240mg / dL, 241mg / dL, 242mg / d L, 243mg / dL, 244mg / dL, 245mg / dL, 246mg / dL, 247mg / dL, 248mg / dL, 249mg / dL, 250mg / dL, 251mg / dL, 252mg / dL, 253mg / dL, 254mg / dL, 255mg / dL, 256mg / dL, 257mg / dL, 258mg / dL, 259mg / dL, 260mg / dL, 26 dL, 215 mg / dL, 216 mg / dL, 217 mg / dL, 218 mg / dL, 219 mg / dL, 220 mg / dL, 221 mg / dL, 222 mg / dL, 223 mg / dL, 224 mg / dL, 225 mg / dL, 226 mg / dL, 227 mg / dL, 228 mg / dL, 229 mg / dL, 230 mg / dL, 231 mg / dL, 232 mg / dL, 233 mg / dL, 234 mg / dL, 235 mg / dL, or about 236 mg / dL, or any concentration above about 236 mg / dL, then the individual exhibits abnormal glycemic control.

[0097] In some embodiments, during an oral glucose tolerance test, when the second blood glucose level is measured 2 hours after the individual orally ingests 75 g of glucose or a sugar dissolved in an aqueous medium, if the second blood glucose level is above about 100 mg / dL, such as about 101 mg / dL, 102 mg / dL, 103 mg / dL, 104 mg / dL, 105 mg / dL, 106 mg / dL, 107 mg / dL, 108 mg / dL, 109 mg / dL, 110 mg / dL, 111 mg / dL, 112 mg / dL, 113 mg / dL, 114 mg / dL, 115 mg / dL, 116 mg / dL, 117 mg / dL, 118 mg / dL, 119 mg / dL, 200 mg / dL, 201 mg / dL 19mg / dL, 120mg / dL, 121mg / dL, 122mg / dL, 123mg / dL, 124mg / dL, 125mg / dL, 126mg / dL, 127mg / dL, 128mg / dL, 129mg / dL, 130mg / dL, 131mg / dL, 132mg / dL , 133mg / dL, 134mg / dL, 135mg / dL, 136mg / dL, 137mg / dL, 138mg / dL, 139mg / dL, 140mg / dL, 141mg / dL, 142mg / dL, 143mg / dL, 144mg / dL, 145mg / dL, 146mg / d L, 147mg / dL, 148mg / dL, 149mg / dL, 150mg / dL, 151mg / dL, 152mg / dL, 153mg / dL, 154mg / dL, 155mg / dL, 156mg / dL, 157mg / dL, 158mg / dL, 159mg / dL, 160mg / dL, 161mg / dL, 162mg / dL, 163mg / dL, 164mg / dL, 165mg / dL, 166mg / dL, 167mg / dL, 168mg / dL, 169mg / dL, 170mg / dL, 171mg / dL, 172mg / dL, 173mg / dL, 174 mg / dL, 175mg / dL, 176mg / dL, 177mg / dL, 178mg / dL, 179mg / dL, 180mg / dL, 181mg / dL, 182mg / dL, 183mg / dL, 184mg / dL, 185mg / dL, 186mg / dL, 187mg / dL, 1 88mg / dL, 189mg / dL, 190mg / dL, 191mg / dL, 192mg / dL, 193mg / dL, 194mg / dL, 195mg / dL, 196mg / dL, 197mg / dL, 198mg / dL, 199mg / dL, 200mg / dL, 201mg / dL,202mg / dL, 203mg / dL, 204mg / dL, 205mg / dL, 206mg / dL, 207mg / dL, 208mg / dL, 209mg / dL, 210mg / dL, 211mg / dL, 212mg / dL, 213mg / dL, 214mg / dL, 215mg / dL, 216mg / dL, 217mg / dL, 218mg / dL, 219mg / dL, 220mg / dL, 221 mg / dL, 222mg / dL, 223mg / dL, 224mg / dL, 225mg / dL, 226mg / dL, 227mg / dL, 228mg / dL, 229mg / dL, 230mg / dL, 231mg / dL, 232mg / dL, 233mg / dL, 234mg / dL, 235mg / dL, 236mg / dL, 237mg / dL, 238mg / dL, 239mg / dL, 240mg / d L, 241mg / dL, 242mg / dL, 243mg / dL, 244mg / dL, 245mg / dL, 246mg / dL, 247mg / dL, 248mg / dL, 249mg / dL, 250m g / dL, 251mg / dL, 252mg / dL, 253mg / dL, 254mg / dL, 255mg / dL, 256mg / dL, 257mg / dL, 258mg / dL, 259mg / dL, 26 If the individual has an abnormal glycemic control, the individual may have an abnormal glycemic control if the individual has an glycemic control of about 275 mg / dL, about 0 mg / dL, about 261 mg / dL, about 262 mg / dL, about 263 mg / dL, about 264 mg / dL, about 265 mg / dL, about 266 mg / dL, about 267 mg / dL, about 268 mg / dL, about 269 mg / dL, about 270 mg / dL, about 271 mg / dL, about 272 mg / dL, about 273 mg / dL, about 274 mg / dL, or about 275 mg / dL.

[0098] In certain embodiments, the blood sugar control test includes the measurement of fasting blood sugar. In certain embodiments, the measurement of fasting blood sugar includes subjecting the individual to fasting. In certain embodiments, the fasting continues overnight. In certain embodiments, the fasting continues for about 6 hours to about 18 hours, for example, about 6 hours, 6.5 hours, 7 hours, 7.5 hours, 8 hours, 8.5 hours, 9 hours, 9.5 hours, 10 hours, 10.5 hours, 11 hours, 11.5 hours, 12 hours, 12.5 hours, 13 hours, 13.5 hours, 14 hours, 14.5 hours, 15 hours, 15.5 hours, 16 hours, 16.5 hours, 17 hours, 17.5 hours, or 18 hours or any duration therebetween. In some embodiments, the fasting lasts from about 6 hours to about 18 hours, from about 6 hours to about 17.5 hours, from about 6 hours to about 17 hours, from about 6 hours to about 16.5 hours, from about 6 hours to about 16 hours, from about 6 hours to about 15.5 hours, from about 6 hours to about 15 hours, from about 6 hours to about 14.5 hours, from about 6 hours to about 14 hours, from about 6 hours to about 13.5 hours, from about 6 hours to about 13 hours, from about 6 hours to about 12.5 hours, from about 6 hours to about 12 hours, from about 6 hours to about 11.5 hours, from about 6 hours to about 15 hours. to about 11 hours, about 6 hours to about 10.5 hours, about 6 hours to about 10 hours, about 6 hours to about 9.5 hours, about 6 hours to about 9 hours, about 6 hours to about 8.5 hours, about 6 hours to about 8 hours, about 6 hours to about 7.5 hours, about 6 hours to about 7 hours, about 6 hours to about 6.5 hours, about 7 hours to about 18 hours, about 7 hours to about 17.5 hours, about 7 hours to about 17 hours, about 7 hours to about 16.5 hours, about 7 hours to about 16 hours, about 7 hours to about 15.5 hours, about 7 hours to about 15 hours, about 7 hours to about 14.5 hours, about 7 hours to about 14 hours, about 7 hours to about 13.5 hours, about 7 hours to about 13 hours, about 7 hours to about 12.5 hours, about 7 hours to about 12 hours, about 7 hours to about 11.5 hours, about 7 hours to about 11 hours, about 7 hours to about 10.5 hours, about 7 hours to about 10 hours, about 7 hours to about 9.5 hours, about 7 hours to about 9 hours, about 7 hours to about 8.5 hours, about 7 hours to about 8 hours, about 7 hours to about 7.5 hours, about 8 hours. Hours to about 18 hours, about 8 hours to about 17.5 hours, about 8 hours to about 17 hours, about 8 hours to about 16.5 hours, about 8 hours to about 16 hours, about 8 hours to about 15.5 hours, about 8 hours to about 15 hours, about 8 hours to about 14.5 hours, about 8 hours to about 14 hours, about 8 hours to about 13.5 hours, about 8 hours to about 13 hours, about 8 hours to about 12.5 hours, about 8 hours to about 12 hours, about 8 hours to about 11.5 hours, about 8 hours to about 11 hours, about 8 hours to about 10.5 hours, about 8 hours to about 10 hours, about 8 hours to about 9.5 hours, about 8 hours to about 9 hours, about 8 hours to about 8.5 hours, about 9 hours to about 18 hours, about 9 hours to about 17.5 hours, about 9 hours to about 17 hours, about 9 hours to about 16.5 hours, about 9 hours to about 16 hours, about 9 hours to about 15.5 hours, about 9 hours to about 15 hours, about 9 hours to about 14.5 hours, about 9 hours to about 14 hours, about 9 hours to about 13.5 hours, about 9 hours to about 13 hours, about 9 hours to about 12.5 hours, about 9 hours to about 12 hours, about 9 hours to about 11.5 hours, about 9 hours to about 11 hours, about 9 hours to about 10.5 hours, about 9 hours to about 10 hours, about 9 hours to about 9.5 hours, about 10 hours to about 18 hours, about 10 hours to about 17.5 hours, about 10 hours to about 17 hours, about 10 hours to about 16.5 hours, about 10 hours to about 16 hours, about 10 hours to about 15.5 hours, about 10 hours to about 15 hours, about 10 hours to about 14.5 hours, about 10 hours to about 14 hours, about 10 hours to about 13.5 hours, about 10 hours to about 13 hours, about 10 hours to about 12.5 hours, about 10 hours to about 12 hours, about 10 hours to about 11.5 hours, about 10 hours to about 11 hours, about 10 hours to about 10.5 hours, about 11 hours to about 18 hours, about 11 hours to about 17. 5 hours, about 11 hours to about 17 hours, about 11 hours to about 16.5 hours, about 11 hours to about 16 hours, about 11 hours to about 15.5 hours, about 11 hours to about 15 hours, about 11 hours to about 14.5 hours, about 11 hours to about 14 hours, about 11 hours to about 13.5 hours, about 11 hours to about 13 hours, about 11 hours to about 12.5 hours, about 11 hours to about 12 hours, about 11 hours to about 11.5 hours, about 12 hours to about 18 hours, about 12 hours to about 17.5 hours, about 12 hours to about 17 hours, about 12 hours to about 16.5 hours, about 12 hours to about 16 hours, about 12 hours to about 15.5 hours, about 12 hours to about 15 hours, about 12 hours to about 14.5 hours, about 12 hours to about 14 hours, about 12 hours to about 13.5 hours, about 12 hours to about 13 hours, about 12 hours to about 12.5 hours, about 13 hours to about 18 hours, about 13 hours to about 17.5 hours, about 13 hours to about 17 hours, about 13 hours to about 16.5 hours, about 13 hours to about 16 hours, about 13 hours to about 15.5 hours, about 13 hours to about 15 hours, about 13 hours to about 14.5 hours, about 13 hours to about 14 hours, about 13 hours to about 13.5 hours, about 14 hours to about 18 hours, about 14 hours to about 17.5 hours, about 14 hours to about 17 hours, about 14 hours to about 16.5 hours5 hours, about 14 hours to about 16 hours, about 14 hours to about 15.5 hours, about 14 hours to about 15 hours, about 14 hours to about 14.5 hours, about 15 hours to about 18 hours, about 15 hours to about 17.5 hours, about 15 hours to about 17 hours, about 15 hours to about 16.5 hours, about 15 hours to about 16 hours, about 15 hours to about 15.5 hours, about 16 hours to about 18 hours, about 16 hours to about 17.5 hours, about 16 hours to about 17 hours, about 16 hours to about 16.5 hours, about 17 hours to about 18 hours, or about 17 hours to about 17.5 hours. .

[0099] In some embodiments, the measurement of the fasting blood glucose test includes measuring the blood glucose level of the individual after fasting. In some embodiments, if the blood glucose level of the individual after fasting is no more than about 150mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is no more than about 149mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is no more than about 148mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is no more than about 147mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is no more than about 146mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is no more than about 145mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is no more than about 144mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is no more than about 143mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 142mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 141mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 140mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 139mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 138mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 137mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 136mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 135mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 134 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 133 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 132 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 131 mg / dL, the individual exhibits normal blood glucose control.In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 130mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 129mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 128mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 127mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 126mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 125mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 124mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 123mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 122mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 121mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 120mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 119mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 118mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 117mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 116mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 115mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual's blood sugar level after fasting does not exceed about 114 mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the individual's blood sugar level after fasting does not exceed about 113 mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the individual's blood sugar level after fasting does not exceed about 112 mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the individual's blood sugar level after fasting does not exceed about 111 mg / dL, the individual exhibits normal blood sugar control.In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 110mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 109mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 108mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 107mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 106mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 105mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 104mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 103mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 102 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 101 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 100 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 99 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 98 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 97 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 96 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 95 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 94 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting does not exceed about 93 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting does not exceed about 92 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting does not exceed about 91 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting does not exceed about 90 mg / dL, the individual exhibits normal blood glucose control.In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 89 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 88 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 87 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 86 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 85 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 84 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 83 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 82 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting does not exceed about 81 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 80 mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 79 mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 78 mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 77 mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 76 mg / dL, the individual exhibits normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting does not exceed about 75 mg / dL, the individual exhibits normal blood sugar control.

[0100] In some embodiments, if an individual's blood glucose level is between about 0 and about 150 mg / dL after fasting, such as about 1 mg / dL, 2 mg / dL, 3 mg / dL, 4 mg / dL, 5 mg / dL, 6 mg / dL, 7 mg / dL, 8 mg / dL, 9 mg / dL, 10 mg / dL, 11 mg / dL, 12 mg / dL, 13 mg / dL, 14 mg / dL, 15 mg / dL, 16 mg / dL, 17 mg / dL, 18 mg / dL, 19 mg / dL, 20 mg / dL, 21 mg / dL, 22 mg / dL, 23 mg / dL, 24 mg / dL, 25 mg / dL, 26 mg / dL, 27 mg / dL, 28 mg / dL, 29 mg / dL, 30 mg / dL, 31 mg / dL, 32 mg / dL, 33 mg / dL, 34 mg / dL, 35 mg / dL, 36 mg / dL, 37 mg / dL, 38 mg / dL, 39 mg / dL, 40 mg / dL, 41 mg / dL, 42 mg / dL, 43 mg / dL, 44 mg / dL, 45 mg / dL, 46 mg / dL, 47 mg / dL, 48 mg / dL, 49 mg / dL, 50 mg / dL, 51 mg / dL, 52 mg / dL, 53 mg / dL, 54 mg / dL, 55 mg / dL, 56 mg / dL, 57 mg / dL, 58 mg / dL, 59 mg / dL, 60 mg / dL, 61 mg / dL, 62 mg / dL, 63 mg / dL, 64 mg / dL, 65 mg / dL, 66 mg / dL, 67 mg / dL, 68 mg / dL, 69 mg / dL, 70 mg / dL, 71 mg / dL, 72 mg / dL, 73 mg / dL, 74 mg / dL, 75 mg / dL, 76 mg / dL, 77 mg / dL, 78 mg / dL, 79 mg / dL, 80 mg / dL, 81 mg / dL, 82 mg / dL, 83 mg / dL, 84 mg / dL, 85 mg / dL, 86 mg / dL, 87 mg / dL, 88 mg / dL, 89 mg / dL, 90 mg / dL, 91 mg / dL, 92 mg / dL, 93 mg / dL, 94 mg / dL, 95 mg / dL, 96 mg / dL, 97 mg / dL, 98 mg / dL, 99 mg / dL, 100 mg / dL, 101 mg / dL, 102 mg / dL, 103 mg / dL, 104 mg / dL, 105 mg / dL, 106 mg / dL, 107 mg / dL, 108 mg / dL, 109 mg / dL, 110 mg / dL, 111 mg / dL, 112 mg / dL, 113 mg / dL, 114 mg / dL, 115 mg / dL, 116 mg / dL, 117 mg / dL, 118 mg / dL,119mg / dL, 120mg / dL, 121mg / dL, 122mg / dL, 123mg / dL, 124mg / dL, 125mg / dL, 126mg / dL, 127mg / dL, 128mg / dL, 129mg / dL, 130mg / dL, 131mg / dL, 132mg / dL, 133mg / dL, 134mg / dL, 135mg / dL, 136 If the individual's blood sugar level is about 100 mg / dL, 112 mg / dL, 113 mg / dL, 114 mg / dL, 115 mg / dL, 116 mg / dL, 117 mg / dL, 118 mg / dL, 119 mg / dL, 120 mg / dL, 121 mg / dL, 122 mg / dL, 123 mg / dL, 124 mg / dL, 125 mg / dL, 126 mg / dL, 127 mg / dL, 128 mg / dL, 129 mg / dL, 130 mg / dL, 131 mg / dL, 132 mg / dL, 133 mg / dL, 134 mg / dL, 135 mg / dL, 136 mg / dL, 137 mg / dL, 138 mg / dL, 139 mg / dL, 140 mg / dL, 141 mg / dL, 142 mg / dL, 143 mg / dL, 144 mg / dL, 145 mg / dL, 146 mg / dL, 147 mg / dL, 148 mg / dL, 149 mg / dL, or about 150 mg / dL, or any concentration therebetween, the individual exhibits normal glycemic control.

[0101] In some embodiments, if the blood glucose level of an individual does not exceed about 150 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 149 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 148 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 147 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 146 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 145 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 144 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 143 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 142mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 141mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 140mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 139mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 138mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 137mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 136mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 135mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual does not exceed about 134 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual does not exceed about 133 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual does not exceed about 132 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of the individual does not exceed about 131 mg / dL after fasting overnight, the individual exhibits normal blood glucose control.In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 130mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 129mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 128mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 127mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 126mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 125mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 124mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 123mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 122mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 121mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 120mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 119mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 118mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 117mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 116mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 115mg / dL, the individual shows normal blood glucose control. In some embodiments, if the individual's blood sugar level does not exceed about 114 mg / dL after fasting overnight, the individual exhibits normal blood sugar control. In some embodiments, if the individual's blood sugar level does not exceed about 113 mg / dL after fasting overnight, the individual exhibits normal blood sugar control. In some embodiments, if the individual's blood sugar level does not exceed about 112 mg / dL after fasting overnight, the individual exhibits normal blood sugar control. In some embodiments, if the individual's blood sugar level does not exceed about 111 mg / dL after fasting overnight, the individual exhibits normal blood sugar control.In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 110mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 109mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 108mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 107mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 106mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 105mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 104mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting overnight is no more than about 103mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 102 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 101 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 100 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 99 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 98 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 97 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 96 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the blood glucose level of an individual does not exceed about 95 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the individual's blood glucose level does not exceed about 94 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the individual's blood glucose level does not exceed about 93 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the individual's blood glucose level does not exceed about 92 mg / dL after fasting overnight, the individual exhibits normal blood glucose control. In some embodiments, if the individual's blood glucose level does not exceed about 91 mg / dL after fasting overnight, the individual exhibits normal blood glucose control.In some embodiments, if the blood sugar level of the individual after fasting overnight is no more than about 90mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting overnight is no more than about 89mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting overnight is no more than about 88mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting overnight is no more than about 87mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting overnight is no more than about 86mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting overnight is no more than about 85mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting overnight is no more than about 84mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood sugar level of the individual after fasting overnight is no more than about 83mg / dL, the individual shows normal blood sugar control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 82mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 81mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 80mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 79mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 78mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 77mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 76mg / dL, the individual shows normal blood glucose control. In some embodiments, if the blood glucose level of an individual after fasting overnight is no more than about 75mg / dL, the individual shows normal blood glucose control.

[0102] In some embodiments, if the subject's blood glucose level after an overnight fast is between about 0 and about 150 mg / dL, e.g., about 1 mg / dL, 2 mg / dL, 3 mg / dL, 4 mg / dL, 5 mg / dL, 6 mg / dL, 7 mg / dL, 8 mg / dL, 9 mg / dL, 10 mg / dL, 11 mg / dL, 12 mg / dL, 13 mg / dL, 14 mg / dL, 15 mg / dL, 16 mg / dL, 17 mg / dL, 18 mg / dL, 19 mg / dL, 20 mg / dL, 21 mg / dL, 22 mg / dL, 23 mg / dL, 24 mg / dL, 25 mg / dL, 26 mg / dL, 27 mg / dL , 28mg / dL, 29mg / dL, 30mg / dL, 31mg / dL, 32mg / dL, 33mg / dL, 34mg / dL, 35mg / dL, 36mg / dL, 37mg / dL, 38mg / dL, 39mg / dL, 40mg / dL, 41mg / dL, 42mg / dL, 43m g / dL, 44mg / dL, 45mg / dL, 46mg / dL, 47mg / dL, 48mg / dL, 49mg / dL, 50mg / dL, 51mg / dL, 52mg / dL, 53mg / dL, 54mg / dL, 55mg / dL, 56mg / dL, 57mg / dL, 58mg / dL, 59mg / dL, 60mg / dL, 61mg / dL, 62mg / dL, 63mg / dL, 64mg / dL, 65mg / dL, 66mg / dL, 67mg / dL, 68mg / dL, 69mg / dL, 70mg / dL, 71mg / dL, 72mg / dL, 73mg / dL, 74mg 9 1 05mg / dL, 106mg / dL, 107mg / dL, 108mg / dL, 109mg / dL, 110mg / dL, 111mg / dL, 112mg / dL, 113mg / dL, 114mg / dL, 115mg / dL, 116mg / dL, 117mg / dL, 118mg / dL,119mg / dL, 120mg / dL, 121mg / dL, 122mg / dL, 123mg / dL, 124mg / dL, 125mg / dL, 126mg / dL, 127mg / dL, 128mg / dL, 129mg / dL, 130mg / dL, 131mg / dL, 132mg / dL, 133mg / dL, 134mg / dL, 135mg / dL, 136 If the individual's blood sugar level is about 100 mg / dL, 112 mg / dL, 113 mg / dL, 114 mg / dL, 115 mg / dL, 116 mg / dL, 117 mg / dL, 118 mg / dL, 119 mg / dL, 120 mg / dL, 121 mg / dL, 122 mg / dL, 123 mg / dL, 124 mg / dL, 125 mg / dL, 126 mg / dL, 127 mg / dL, 128 mg / dL, 129 mg / dL, 130 mg / dL, 131 mg / dL, 132 mg / dL, 133 mg / dL, 134 mg / dL, 135 mg / dL, 136 mg / dL, 137 mg / dL, 138 mg / dL, 139 mg / dL, 140 mg / dL, 141 mg / dL, 142 mg / dL, 143 mg / dL, 144 mg / dL, 145 mg / dL, 146 mg / dL, 147 mg / dL, 148 mg / dL, 149 mg / dL, or about 150 mg / dL, or any concentration therebetween, the individual exhibits normal glycemic control.

[0103] In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 150mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 149mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 148mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 147mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 146mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 145mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 144mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 143mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 142mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 141mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 140mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 139mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 138 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 137 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 136 mg / dL, the individual exhibits normal blood glucose control.In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 135mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 134mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 133mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 132mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 131mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 130mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 129mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 128mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 127mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 126mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 125mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 124mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 123 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 122 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 121 mg / dL, the individual exhibits normal blood glucose control.In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 120mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 119mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 118mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 117mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 116mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 115mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 114 mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 113 mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 112 mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 111 mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 110 mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 109 mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 108 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 107 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 106 mg / dL, the individual exhibits normal blood glucose control.In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 105mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 104mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 103mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 102mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 101mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 100mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting does not exceed about 99 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting does not exceed about 98 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting does not exceed about 97 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting does not exceed about 96 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting does not exceed about 95 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting does not exceed about 94 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is no more than about 93 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is no more than about 92 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is no more than about 91 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is no more than about 90 mg / dL, the individual shows normal blood glucose control.In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is no more than about 89 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is no more than about 88 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is no more than about 87 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is no more than about 86 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is no more than about 85 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is no more than about 84 mg / dL, the individual shows normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 83mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 82mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 81mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 80mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 79mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood sugar level of the individual after fasting is no more than about 78mg / dL, the individual shows normal blood sugar control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 77 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 76 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the individual's blood glucose level after fasting does not exceed about 75 mg / dL, the individual exhibits normal blood glucose control.

[0104] In some embodiments, normal glycemic control is established on the day of administration of the IGF1R inhibitor. In some embodiments, normal glycemic control is established 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 21, 28, 35, 42, 48, or 56 days prior to administration of the IGF1R inhibitor.

[0105] In some embodiments, when fasting lasts for about 8 to about 16 hours, if after fasting the individual's blood glucose level is between 0 and about 150 mg / dL, e.g., about 1 mg / dL, 2 mg / dL, 3 mg / dL, 4 mg / dL, 5 mg / dL, 6 mg / dL, 7 mg / dL, 8 mg / dL, 9 mg / dL, 10 mg / dL, 11 mg / dL, 12 mg / dL, 13 mg / dL, 14 mg / dL, 15 mg / dL, 16 mg / dL, 17 mg / dL, 18 mg / dL, 19 mg / dL, 20 mg / dL, 21 mg / dL, 22 mg / dL, 23 mg / dL, 24 mg / dL, 25 mg / dL, 26 mg / dL 4 2mg / dL, 43mg / dL, 44mg / dL, 45mg / dL, 46mg / dL, 47mg / dL, 48mg / dL, 49mg / dL, 50mg / dL, 51mg / dL, 52mg / dL, 53mg / dL, 54mg / dL, 55mg / dL, 56mg / dL, 57mg / d L, 58mg / dL, 59mg / dL, 60mg / dL, 61mg / dL, 62mg / dL, 63mg / dL, 64mg / dL, 65mg / dL, 66mg / dL, 67mg / dL, 68mg / dL, 69mg / dL, 70mg / dL, 71mg / dL, 72mg / dL, 73m g / dL, 74mg / dL, 75mg / dL, 76mg / dL, 77mg / dL, 78mg / dL, 79mg / dL, 80mg / dL, 81mg / dL, 82mg / dL, 83mg / dL, 84mg / dL, 85mg / dL, 86mg / dL, 87mg / dL, 88mg / dL, 89mg / dL、90mg / dL、91mg / dL、92mg / dL、93mg / dL、94mg / dL、95mg / dL、96mg / dL、97mg / dL、98mg / dL、99mg / dL、100mg / dL、101mg / dL、102mg / dL、103mg / dL 04mg / dL, 105mg / dL, 106mg / dL, 107mg / dL, 108mg / dL, 109mg / dL, 110mg / dL, 111mg / dL, 112mg / dL, 113mg / dL, 114mg / dL, 115mg / dL, 116mg / dL, 117mg / dL,118mg / dL, 119mg / dL, 120mg / dL, 121mg / dL, 122mg / dL, 123mg / dL, 124mg / dL, 125mg / dL, 126mg / dL , 127mg / dL, 128mg / dL, 129mg / dL, 130mg / dL, 131mg / dL, 132mg / dL, 133mg / dL, 134mg / dL, 135mg / dL dL, 136 mg / dL, 137 mg / dL, 138 mg / dL, 139 mg / dL, 140 mg / dL, 141 mg / dL, 142 mg / dL, 143 mg / dL, 144 mg / dL, 145 mg / dL, 146 mg / dL, 147 mg / dL, 148 mg / dL, 149 mg / dL, or about 150 mg / dL, or any concentration therebetween, the individual exhibits normal glycemic control.

[0106] In some embodiments, if the blood glucose level of the individual after fasting is higher than about 150mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 149mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 148mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 147mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 146mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 145mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 144mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 143mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 142 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 141 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 140 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 139 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 138 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 137 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 136 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 135 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 134 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 133 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 132 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 131 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 130 mg / dL, the individual exhibits abnormal blood glucose control.In some embodiments, if the blood glucose level of the individual after fasting is higher than about 129 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 128 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 127 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 126 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 125 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 124 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 123 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 122 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 121 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 120 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 119 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 118 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 117 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 116 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 115 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 114 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 113 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 112 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 111 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 110 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 109 mg / dL, the individual exhibits abnormal blood glucose control.In some embodiments, if the blood glucose level of the individual after fasting is higher than about 108 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 107 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 106 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 105 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 104 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 103 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 102 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual after fasting is higher than about 101 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 100 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 99 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 98 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 97 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 96 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 95 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 94 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 93 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 92 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is above about 91 mg / dL, the individual exhibits abnormal glycemic control. In some embodiments, if the individual's blood glucose level after fasting is above about 90 mg / dL, the individual exhibits abnormal glycemic control. In some embodiments, if the individual's blood glucose level after fasting is above about 89 mg / dL, the individual exhibits abnormal glycemic control. In some embodiments, if the individual's blood glucose level after fasting is above about 88 mg / dL, the individual exhibits abnormal glycemic control.In some embodiments, if the individual's blood glucose level after fasting is higher than about 87 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 86 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 85 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 84 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 83 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 82 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 81 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 80 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is higher than about 79 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level after fasting is above about 78 mg / dL, the individual exhibits abnormal glycemic control. In some embodiments, if the individual's blood glucose level after fasting is above about 77 mg / dL, the individual exhibits abnormal glycemic control. In some embodiments, if the individual's blood glucose level after fasting is above about 76 mg / dL, the individual exhibits abnormal glycemic control. In some embodiments, if the individual's blood glucose level after fasting is above about 75 mg / dL, the individual exhibits abnormal glycemic control.

[0107] In some embodiments, if the individual's blood glucose level after fasting is above about 75 mg / dL, such as about 76 mg / dL, 77 mg / dL, 78 mg / dL, 79 mg / dL, 80 mg / dL, 81 mg / dL, 82 mg / dL, 83 mg / dL, 84 mg / dL, 85 mg / dL, 86 mg / dL, 87 mg / dL, 88 mg / dL, 89 mg / dL, 90 mg / dL, 91 mg / dL, 92 mg / dL, 93 mg / dL , 94mg / dL, 95mg / dL, 96mg / dL, 97mg / dL, 98mg / dL, 99mg / dL, 100mg / dL, 101mg / dL, 102mg / dL, 103mg / dL, 104mg / dL, 105mg / dL, 106mg / dL, 107mg / dL, 108mg / dL, 109mg / dL, 110mg / dL, 111mg / dL, 112mg / dL, 113mg / dL, 114mg / dL, 115mg / dL, 116mg / dL, 117mg / dL, 118mg / dL, 119mg / dL, 120mg / dL, 121mg / dL, 122mg / dL, 123mg / dL, 124m g / dL, 125mg / dL, 126mg / dL, 127mg / dL, 128mg / dL, 129mg / dL, 130mg / dL, 131mg / dL, 132mg / dL, 133mg / dL, 134m g / dL, or any concentration above 150 mg / dL, the individual exhibits abnormal glycemic control.

[0108] In some embodiments, if the blood glucose level of an individual is higher than about 150 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 149 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 148 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 147 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 146 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 145 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 144 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 143 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 142 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 141 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 140 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 139 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 138 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 137 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 136 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 135 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 134 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 133 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 132 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 131 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control.In some embodiments, if the blood glucose level of the individual is higher than about 130 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 129 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 128 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 127 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 126 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 125 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 124 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 123 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 122 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 121 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 120 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 119 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 118 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 117 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 116 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 115 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 114 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 113 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 112 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 111 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control.In some embodiments, if the blood glucose level of the individual is higher than about 110 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 109 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 108 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 107 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 106 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 105 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 104 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of the individual is higher than about 103 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 102 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 101 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 100 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 99 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 98 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 97 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 96 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 95 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 94 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 93 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 92 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control. In some embodiments, if the individual's blood glucose level is above about 91 mg / dL after an overnight fast, the individual exhibits abnormal blood glucose control.In some embodiments, if the blood glucose level of an individual is higher than about 90 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 89 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 88 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 87 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 86 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 85 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 84 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 83 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 82 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 81 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 80 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 79 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 78 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 77 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 76 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control. In some embodiments, if the blood glucose level of an individual is higher than about 75 mg / dL after fasting overnight, the individual exhibits abnormal blood glucose control.

[0109] In some embodiments, if the subject's blood glucose level after an overnight fast is above about 75 mg / dL, e.g., about 76 mg / dL, 77 mg / dL, 78 mg / dL, 79 mg / dL, 80 mg / dL, 81 mg / dL, 82 mg / dL, 83 mg / dL, 84 mg / dL, 85 mg / dL, 86 mg / dL, 87 mg / dL, 88 mg / dL, 89 mg / dL, 90 mg / dL, 91 mg / dL, 92 mg / dL, 93 mg / dL L, 94mg / dL, 95mg / dL, 96mg / dL, 97mg / dL, 98mg / dL, 99mg / dL, 100mg / dL, 101mg / dL, 102mg / dL, 103mg / dL, 104m g / dL, 105mg / dL, 106mg / dL, 107mg / dL, 108mg / dL, 109mg / dL, 110mg / dL, 111mg / dL, 112mg / dL, 113mg / dL, 114m g / dL, 115mg / dL, 116mg / dL, 117mg / dL, 118mg / dL, 119mg / dL, 120mg / dL, 121mg / dL, 122mg / dL, 123mg / dL, 124m g / dL, 125mg / dL, 126mg / dL, 127mg / dL, 128mg / dL, 129mg / dL, 130mg / dL, 131mg / dL, 132mg / dL, 133mg / dL, 134m g / dL, 135 mg / dL, 136 mg / dL, 137 mg / dL, 138 mg / dL, 139 mg / dL, 140 mg / dL, 141 mg / dL, 142 mg / dL, 143 mg / dL, 144 mg / dL, 145 mg / dL, 146 mg / dL, 147 mg / dL, 148 mg / dL, 149 mg / dL, or any concentration about 150 mg / dL, or above 150 mg / dL, then the individual exhibits abnormal glycemic control.

[0110] In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 150mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 149mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 148mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 147mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 146mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 145mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 144 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 143 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 142 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 141 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 140 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 139 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 138 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 137 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 136 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 135 mg / dL, the individual exhibits abnormal blood glucose control.In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 134 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 133 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 132 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 131 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 130 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 129 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 128mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 127mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 126mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 125mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 124mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 123mg / dL, the individual shows abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 122 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 121 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 120 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 119 mg / dL, the individual exhibits abnormal blood glucose control.In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 118 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 117 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 116 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 115 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 114 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 113 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 112 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 111 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 110 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 109 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 108 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 107 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 106 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 105 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 104 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 103 mg / dL, the individual exhibits abnormal blood glucose control.In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 102 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 101 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 100 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 99 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 98 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 97 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 96 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 95 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 94 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 93 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 92 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 91 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 90 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 89 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 88 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 87 mg / dL, the individual exhibits abnormal blood glucose control.In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 86 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 85 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 84 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 83 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 82 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 81 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 80 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 79 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 78 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 77 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 76 mg / dL, the individual exhibits abnormal blood glucose control. In some embodiments, when fasting lasts for about 8 to about 16 hours, if the blood glucose level of the individual after fasting is higher than about 75 mg / dL, the individual exhibits abnormal blood glucose control.

[0111] In some embodiments, when fasting lasts for about 8 to about 16 hours, if after fasting the individual's blood glucose level is above about 75 mg / dL, e.g., about 76 mg / dL, 77 mg / dL, 78 mg / dL, 79 mg / dL, 80 mg / dL, 81 mg / dL, 82 mg / dL, 83 mg / dL, 84 mg / dL, 85 mg / dL, 86 mg / dL, 87 mg / dL, 88 mg / dL, 89 mg / dL, 90 mg / dL, 91 mg / dL, 92 mg / dL / dL, 93mg / dL, 94mg / dL, 95mg / dL, 96mg / dL, 97mg / dL, 98mg / dL, 99mg / dL, 100mg / dL, 101mg / dL, 102mg / dL, 103mg / dL, 104mg / dL, 105mg / dL, 106mg / dL, 107mg / dL, 108mg / dL, 109mg / dL, 110mg / dL, 111mg / dL, 112mg / dL, 113mg / d L, 114mg / dL, 115mg / dL, 116mg / dL, 117mg / dL, 118mg / dL, 119mg / dL, 120mg / dL, 121mg / dL, 122mg / dL, 123mg / dL , 124mg / dL, 125mg / dL, 126mg / dL, 127mg / dL, 128mg / dL, 129mg / dL, 130mg / dL, 131mg / dL, 132mg / dL, 133mg / dL, 1 or any concentration about 150 mg / dL, or above 150 mg / dL, then the individual exhibits abnormal glycemic control.

[0112] In some embodiments, the blood glucose control test includes the measurement of non-fasting blood glucose. In some embodiments, the measurement of non-fasting blood glucose includes measuring the blood glucose level or blood glucose level of the individual without subjecting the individual to fasting. In some embodiments, the measurement of non-fasting blood glucose includes measuring the blood glucose level or blood glucose level of the individual at any time without subjecting the individual to fasting.

[0113] In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 250 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 249 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 248 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 247 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 246 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 245 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 244 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 243 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 242 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 241 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 240 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 239 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 238 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 237 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 236 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 235 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 234 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 233 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 232 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 231 mg / dL, the individual exhibits normal blood glucose control.In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 230 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 229 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 228 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 227 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 226 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 225 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 224 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 223 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 222 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 221 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 220 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 219 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 218 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 217 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 216 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 215 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level of less than about 214 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level of less than about 213 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level of less than about 212 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level of less than about 211 mg / dL, the individual exhibits normal blood glucose control.In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 210 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 209 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 208 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 207 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 206 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 205 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 204 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 203 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 202 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 201 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 200 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 199 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 198 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 197 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 196 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 195 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level of less than about 194 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level of less than about 193 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level of less than about 192 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level of less than about 191 mg / dL, the individual exhibits normal blood glucose control.In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 190 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 189 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 188 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 187 mg / dL, the individual exhibits normal blood glucose control. In some embodiments, if the individual exhibits a non-fasting blood glucose level below about 186 mg / dL, the individual exhibits normal blood glucos...

Claims

1. A method of treating an individual suffering from an insulin-like growth factor 1 receptor (IGF1R)-related disorder, the method comprising: a) selecting the individual suffering from the IGF1R-associated disorder for treatment with an antagonist of IGF1R signaling if the individual exhibits normal glycemic control as measured by a glycemic control test; and b) administering to the individual an antagonist of IGF1R signaling.

2. The method of claim 1, wherein the IGF1R-related disorder comprises thyroid eye disease.

3. The method of claim 1 or 2, wherein the antagonist of IGF1R signaling comprises an antibody that binds IGF1R.

4. The method of claim 3, wherein the antibody that binds to IGF1R comprises ganituzumab, fentolumab, MEDI-573, citumumab, darototumumab, rotuximab, AVE1642, BIIB022, centuzumab, estuzumab or lincitinib.

5. The method of claim 3, wherein the antibody that binds to IGF1R comprises tetumumab.

6. The method of claim 1 or 2, wherein the antagonist of IGF1R signaling comprises a small molecule that inhibits IGF1R signaling, and wherein the small molecule that inhibits IGF1R signaling comprises picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, ganetespib, ceritinib, or A-928605.

7. The method of any one of claims 3 to 5, wherein the antibody that binds to IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising the amino acid sequence according to SEQ ID No.: 5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence according to SEQ ID No.: 6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence according to SEQ ID No.: 7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence according to SEQ ID No.: 8; (ii) a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence according to SEQ ID No.: 9; and (iii) a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence according to SEQ ID No.:

10.

8. The method of any one of claims 3-5 and 7, wherein the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

4.

9. The method of any one of claims 3-5, 7 and 8, wherein the antibody that binds to IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

2.

10. The method of any one of claims 3-5 and 7-9, wherein the antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence according to SEQ ID No.: 1; and b) a light chain comprising the amino acid sequence according to SEQ ID No.:

2.

11. The method of claim 1, wherein the blood sugar control test comprises measurement of hemoglobin A1c (HbA1c).

12. The method of claim 11, wherein the subject exhibits normal glycemic control if the hemoglobin A1c (HbA1c) measurement is below about 6.5%.

13. The method of claim 1, wherein the blood glucose control test comprises measurement of fasting blood glucose.

14. The method of claim 13, wherein the subject exhibits normal glycemic control if the subject exhibits a blood glucose level of less than about 126 mg / dL after an overnight fast.

15. A method of treating an individual suffering from an insulin-like growth factor 1 receptor (IGF1R)-related disorder, the method comprising: a) obtaining results of a glycemic control test from the individual; and b) administering to the individual an antagonist of IGF1R signaling if the individual exhibits normal glycemic control as measured by the glycemic control test.

16. The method of claim 15, wherein the IGF1R-related disorder comprises thyroid eye disease.

17. The method of claim 15 or 16, wherein the antagonist of IGF1R signaling comprises an antibody that binds IGF1R.

18. The method of claim 17, wherein the antibody that binds to IGF1R comprises ganituzumab, fentolumab, MEDI-573, citumumab, darototumumab, rotuximab, AVE1642, BIIB022, centuzumab, estuzumab, or lincitinib.

19. The method of claim 17, wherein the antibody that binds to IGF1R comprises tetumumab.

20. The method of claim 15 or 16, wherein the antagonist of IGF1R signaling comprises a small molecule that inhibits IGF1R signaling, and wherein the small molecule that inhibits IGF1R signaling comprises picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, ganetespib, ceritinib, or A-928605.

21. The method of any one of claims 17-19, wherein the antibody that binds to IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising the amino acid sequence according to SEQ ID No.: 5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence according to SEQ ID No.: 6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence according to SEQ ID No.: 7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence according to SEQ ID No.: 8; (ii) a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence according to SEQ ID No.: 9; and (iii) a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence according to SEQ ID No.:

10.

22. The method of any one of claims 17-19 and 21, wherein the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

4.

23. The method of any one of claims 17-19, 21 and 22, wherein the antibody that binds to IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

2.

24. The method of any one of claims 17-19 and 21-23, wherein the antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence according to SEQ ID No.: 1; and b) a light chain comprising the amino acid sequence according to SEQ ID No.:

2.

25. The method of claim 1, wherein the blood glucose control test comprises measurement of hemoglobin A1c (HbA1c).

26. The method of claim 25, wherein if the HbA1c measurement is below about 6.5%, the subject exhibits normal glycemic control.

27. The method of claim 1, wherein the blood glucose control test comprises measurement of fasting blood glucose.

28. The method of claim 27, wherein the subject exhibits normal glycemic control if the subject exhibits a blood glucose level of less than about 126 mg / dL after an overnight fast.

29. A method of monitoring an individual being treated with an antagonist of insulin-like growth factor 1 receptor (IGF1R) signaling, wherein the individual suffers from an IGF1R-related disorder, the method comprising: a) obtaining the results of a glycemic control test from the individual treated with the antagonist of IGF1R signaling; and b) discontinuing treatment of the individual with the antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control as measured by the test for glycemic control.

30. The method of claim 29, wherein the IGF1R-related disorder comprises thyroid eye disease.

31. The method of claim 29 or 30, wherein the antagonist of IGF1R signaling comprises an antibody that binds IGF1R.

32. The method of claim 31, wherein the antibody that binds to IGF1R comprises ganituzumab, fentolumab, MEDI-573, citumumab, darototumumab, rotuximab, AVE1642, BIIB022, centuzumab, estuzumab, or lincitinib.

33. The method of claim 31, wherein the antibody that binds IGF1R comprises tetumumab.

34. The method of claim 29 or 30, wherein the antagonist of IGF1R signaling comprises a small molecule that inhibits IGF1R signaling, and wherein the small molecule that inhibits IGF1R signaling comprises picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, ganetespib, ceritinib, or A-928605.

35. The method of any one of claims 31-33, wherein the antibody that binds IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising the amino acid sequence according to SEQ ID No.: 5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence according to SEQ ID No.: 6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence according to SEQ ID No.: 7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence according to SEQ ID No.: 8; (ii) a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence according to SEQ ID No.: 9; and (iii) a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence according to SEQ ID No.:

10.

36. The method of any one of claims 31-33 and 35, wherein the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

4.

37. The method of any one of claims 31-33, 35 and 36, wherein the antibody that binds IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

2.

38. The method of claim 29, wherein the blood glucose control test comprises measurement of hemoglobin A1c (HbA1c).

39. The method of claim 38, wherein the subject exhibits abnormal glycemic control if the HbA1c measurement is at least about 6.5%.

40. The method of claim 29, wherein the blood glucose control test comprises measurement of fasting blood glucose.

41. The method of claim 40, wherein the individual exhibits abnormal glycemic control if the fasting blood glucose measurement after an overnight fast is at least about 126 mg / dL.

42. The method of claim 29, further comprising obtaining results of a second test of glycemic control from the individual after the discontinuation after treating the individual's abnormal glycemic control.

43. The method of claim 42, further comprising administering to the individual an antagonist of IGF1R signaling if the individual exhibits normal glycemic control by the second test of glycemic control.

44. A method of treating an individual suffering from an insulin-like growth factor 1 receptor (IGF1R)-related disorder, the method comprising: a) administering to the individual a first dose of an antagonist of IGF1R signaling; b) obtaining results of a blood glucose control test from the individual; as well as c) administering to the individual a second dose of the antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control as measured by the glycemic control test, wherein the second dose is lower than the first dose.

45. The method of claim 44, wherein the IGF1R-related disorder comprises thyroid eye disease.

46. ​​The method of claim 44 or 45, wherein the antagonist of IGF1R signaling comprises an antibody that binds IGF1R.

47. The method of claim 46, wherein the antibody that binds to IGF1R comprises ganituzumab, fentolumab, MEDI-573, citumumab, darototumumab, rotuximab, AVE1642, BIIB022, centuzumab, estuzumab, or lincitinib.

48. The method of claim 46, wherein the antibody that binds IGF1R comprises tetumumab.

49. The method of claim 44 or 45, wherein the antagonist of IGF1R signaling comprises a small molecule that inhibits IGF1R signaling, and wherein the small molecule that inhibits IGF1R signaling comprises picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, or A-928605.

50. The method of any one of claims 46-48, wherein the antibody that binds IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising the amino acid sequence according to SEQ ID No.: 5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence according to SEQ ID No.: 6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence according to SEQ ID No.: 7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence according to SEQ ID No.: 8; (ii) a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence according to SEQ ID No.: 9; and (iii) a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence according to SEQ ID No.:

10.

51. The method of any one of claims 46-48 and 50, wherein the antibody that binds IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

4.

52. The method of any one of claims 46-48, 50 and 51, wherein the antibody that binds IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

2.

53. The method of claim 44, wherein the blood glucose control test comprises measurement of hemoglobin A1c (HbA1c).

54. The method of claim 53, wherein the subject exhibits abnormal glycemic control if the HbA1c measurement is about 6.5% or higher.

55. The method of claim 44, wherein the blood glucose control test comprises measurement of fasting blood glucose.

56. The method of claim 55, wherein the subject exhibits abnormal glycemic control if the fasting blood glucose measurement after an overnight fast is about 126 mg / dL or higher.

57. A method of treating an individual suffering from an insulin-like growth factor 1 receptor (IGF1R)-related disorder, the method comprising: a) selecting the individual suffering from the IGF1R-associated disorder for treatment with an antagonist of IGF1R signaling if the individual exhibits normal glycemic control as measured by a first test of glycemic control; b) administering to the individual a first dose of the antagonist of IGF1R signaling; and c) obtaining the results of a second test of glycemic control from the individual treated with the antagonist of IGF1R signaling.

58. The method of claim 57, further comprising discontinuing treatment of the individual with the antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control as determined by the results of the second test of glycemic control.

59. The method of claim 57, further comprising administering to the individual a second dose of the antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control as determined by the results of the second glycemic control test, wherein the second dose is lower than the first dose.

60. The method of claim 57, wherein the IGF1R-related disorder comprises thyroid eye disease.

61. The method of any one of claims 57-60, wherein the antagonist of IGF1R signaling comprises an antibody that binds IGF1R.

62. The method of claim 61, wherein the antibody that binds to IGF1R comprises ganituzumab, fentolumab, MEDI-573, citumumab, darototumumab, rotuximab, AVE1642, BIIB022, centuzumab, estuzumab, or lincitinib.

63. The method of claim 61, wherein the antibody that binds IGF1R comprises tetumumab.

64. The method of any one of claims 57 to 60, wherein the antagonist of IGF1R signaling comprises a small molecule that inhibits IGF1R signaling, and wherein the small molecule that inhibits IGF1R signaling comprises picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, or A-928605.

65. The method of any one of claims 61-63, wherein the antibody that binds IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising the amino acid sequence according to SEQ ID No.: 5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence according to SEQ ID No.: 6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence according to SEQ ID No.: 7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence according to SEQ ID No.: 8; (ii) a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence according to SEQ ID No.: 9; and (iii) a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence according to SEQ ID No.:

10.

66. The method of any one of claims 61-63 and 65, wherein the antibody that binds IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

4.

67. The method of any one of claims 61-63, 65 and 66, wherein the antibody that binds IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

2.

68. The method of claim 57, wherein the first or second blood glucose control test comprises measurement of hemoglobin A1c (HbA1c).

69. The method of claim 68, wherein the subject exhibits abnormal glycemic control if the HbA1c measurement is about 6.5% or higher, wherein the subject exhibits normal glycemic control if the hemoglobin A1c (HbA1c) measurement is below about 6.5%.

70. The method of claim 57, wherein the blood glucose control test comprises measurement of fasting blood glucose.

71. The method of claim 70, wherein the individual exhibits abnormal glycemic control if the fasting blood glucose measurement after an overnight fast is about 126 mg / dL or higher, wherein the individual exhibits normal glycemic control if the individual exhibits a blood glucose level below about 126 mg / dL after an overnight fast.

72. The method of any one of claims 57-71, wherein the method further comprises treating the individual's abnormal blood control if the individual exhibits abnormal blood sugar control as determined by the results of the second blood sugar control test.

73. A method of treating an individual suffering from an insulin-like growth factor 1 receptor (IGF1R)-related disorder, the method comprising: a) obtaining the results of a blood glucose test from the individual; and b) if the individual does not exhibit elevated blood glucose as determined by the blood glucose test, administering to the individual a dose of an antagonist of IGF1R signaling.

74. The method of claim 73, wherein the IGF1R-related disorder comprises thyroid eye disease.

75. The method of claim 73 or 74, wherein the antagonist of IGF1R signaling comprises an antibody that binds IGF1R.

76. The method of claim 75, wherein the antibody that binds to IGF1R comprises ganituzumab, fentolumab, MEDI-573, citumumab, darototumumab, rotuximab, AVE1642, BIIB022, centuzumab, estuzumab, or lincitinib.

77. The method of claim 75, wherein the antibody that binds IGF1R comprises tetumumab.

78. The method of claim 73 or 74, wherein the antagonist of IGF1R signaling comprises a small molecule that inhibits IGF1R signaling, and wherein the small molecule that inhibits IGF1R signaling comprises picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, or A-928605.

79. The method of any one of claims 75-77, wherein the antibody that binds IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising the amino acid sequence according to SEQ ID No.: 5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence according to SEQ ID No.: 6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence according to SEQ ID No.: 7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence according to SEQ ID No.: 8; (ii) a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence according to SEQ ID No.: 9; and (iii) a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence according to SEQ ID No.:

10.

80. The method of any one of claims 75-77 and 79, wherein the antibody that binds IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

4.

81. The method of any one of claims 75-77, 79 and 80, wherein the antibody that binds IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

2.

82. The method of claim 73, wherein the blood glucose test comprises measurement of hemoglobin A1c (HbA1c).

83. The method of claim 82, wherein if the HbA1c measurement is about 6.5% or less, the individual does not exhibit elevated blood glucose.

84. The method of claim 73, wherein the blood glucose test comprises measurement of fasting blood glucose.

85. The method of claim 84, wherein the individual does not exhibit elevated blood glucose if the fasting blood glucose measurement after an overnight fast is less than 126 mg / dL.

86. A method of treating an individual suffering from an insulin-like growth factor 1 receptor (IGF1R)-related disorder, wherein the individual also suffers from diabetes, the method comprising: a. administering one or more antidiabetic drugs to lower blood glucose levels; and b. administering to the individual a dose of an antagonist of IGF1R signaling.

87. The method of claim 86, wherein the IGF1R-related disorder comprises thyroid eye disease.

88. The method of claim 86 or 87, wherein the antagonist of IGF1R signaling comprises an antibody that binds IGF1R.

89. The method of claim 88, wherein the antibody that binds to IGF1R comprises ganituzumab, fentolumab, MEDI-573, citumumab, darototumumab, rotuximab, AVE1642, BIIB022, centuzumab, estuzumab, or lincitinib.

90. The method of claim 89, wherein the antibody that binds IGF1R comprises tetumumab.

91. The method of claim 86 or 87, wherein the antagonist of IGF1R signaling comprises a small molecule that inhibits IGF1R signaling, and wherein the small molecule that inhibits IGF1R signaling comprises picropodophyllin, BMS-754807, BMS-536924, BMS-554417, GSK1838705A, GSK1904529A, NVP-AEW541, NVP-ADW742, GTx-134, AG1024, KW-2450, PL-2258, NVP-AEW541, INSM-18, AZD3463, AZD9362, BI885578, BI893923, TT-100 (NDGA), XL-228, or A-928605.

92. The method of any one of claims 88-90, wherein the antibody that binds IGF1R comprises: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising the amino acid sequence according to SEQ ID No.: 5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence according to SEQ ID No.: 6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence according to SEQ ID No.: 7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence according to SEQ ID No.: 8; (ii) a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence according to SEQ ID No.: 9; and (iii) a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence according to SEQ ID No.:

10.

93. The method of any one of claims 88-90 and 92, wherein the antibody that binds IGF1R comprises: a) a heavy chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 3; and b) a light chain variable domain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

4.

94. The method of any one of claims 88-90, 92, and 93, wherein the antibody that binds IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity to SEQ ID No.:

2.

95. The method of any one of claims 86-94, wherein the one or more antidiabetic drugs are selected from the list consisting of insulin, metformin, pioglitazone, rosiglitazone, acarbose, miglitol, bromocriptine, alogliptin, linagliptin, saxagliptin, sitagliptin, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, telpotide, nateglinide, repaglinide, canagliflozin, dapagliflozin, empagliflozin, erpagliflozin, glimepiride, gliclazide, glipizide, and combinations thereof.

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