Methods and compositions for the treatment of thyroid eye disease

Abstract

Methods and compositions for treating individuals afflicted with insulin-like growth factor 1 receptor (IGF1R)-related diseases using antagonists of IGF1R signaling are provided herein.

Description

Technical Field

[0001] Cross-reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 346,069, filed May 26, 2022, and U.S. Provisional Patent Application No. 63 / 386,528, filed Dec. 8, 2022, both of which are hereby incorporated by reference in their entirety.

Background Art

[0002] Insulin-like growth factor 1 receptor (IGF1R) is a cell surface receptor. IGF1R signaling is involved in many diseases such as Graves' ophthalmopathy, Graves' eye disease, Graves' orbitopathy, and thyroid-associated ophthalmopathy (TAO), also known as thyroid eye disease (TED). Thyroid eye disease affects the thyroid and the eyes, causing inflammation and damage to the eye muscles and connective tissues, which may lead to pain, swelling, orbital deformity, vision loss, or blindness.

[0003] Methods and compositions for the treatment of IGF1R-related diseases such as thyroid eye disease are needed.

[0004] Incorporation by reference All publications, patents, and patent applications mentioned in this specification are hereby incorporated by reference to the same extent as if each individual publication, patent, or patent application had been specifically and individually indicated to be incorporated by reference.

Summary of the Invention

Means for Solving the Problems

[0005] In one aspect, a method for treating an individual suffering from an insulin-like growth factor 1 receptor (IGF1R)-related disease, comprising: a) selecting the individual for treatment with an antagonist of IGF1R signaling if the individual suffering from the IGF1R-related disease shows normal blood glucose management by a blood glucose management test; and b) administering to the individual an antagonist of IGF1R signaling, is provided herein. In some embodiments, the IGF1R-related disease includes thyroid ophthalmopathy. 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, siltuximab, daratumumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumab, or linsitinib. In some embodiments, the antibody that binds to 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 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.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 the amino acid sequence set forth in SEQ ID NO: 5; (ii) a second heavy chain complementarity-determining region (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 6; and (iii) a third heavy chain complementarity-determining region (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 7; and b) a light chain comprising: (i) a first light chain complementarity-determining region (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 8; (ii) a second light chain complementarity-determining region (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 9; and (iii) a third light chain complementarity-determining region (LCDR3) comprising the amino acid sequence set forth in 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 with 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 with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO: 3; and b) a light chain variable domain comprising the amino acid sequence set forth in 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 with SEQ ID NO: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity with SEQ ID NO: 2. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 1; and b) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 2.

[0006] In some embodiments, the blood glucose management 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, the blood glucose management test includes the measurement of hemoglobin A1c (HbA1c). In some embodiments, an individual exhibits normal blood glucose management if the measurement of hemoglobin A1c (HbA1c) is less than about 6.5%. In some embodiments, an individual exhibits normal blood glucose management if the measurement of hemoglobin A1c (HbA1c) is less than about 5.7%. In some embodiments, the blood glucose management test includes an oral glucose tolerance test. In some embodiments, an individual exhibits normal blood glucose management if the individual exhibits a blood glucose level of less than about 200 mg / dL about 2 hours after oral ingestion of about 75 grams of sugar. In some embodiments, an individual exhibits normal blood glucose management if the individual exhibits a blood glucose level of about 140 mg / dL or less about 2 hours after oral ingestion of about 75 grams of sugar. In some embodiments, the blood glucose management test includes the measurement of fasting blood glucose. In some embodiments, an individual exhibits normal blood glucose management if the individual exhibits a blood glucose level of less than about 126 mg / dL after an overnight fast. In some embodiments, an individual exhibits normal blood glucose management if the individual exhibits a blood glucose level of about 99 mg / dL or less after an overnight fast. In some embodiments, the overnight fast lasts at least about 8 hours. In some embodiments, the overnight fast lasts from about 8 to about 16 hours. In some embodiments, the blood glucose management test includes the measurement of non-fasting blood glucose. In some embodiments, an individual exhibits normal blood glucose management if the individual exhibits a non-fasting blood glucose level of less than about 200 mg / dL. In some embodiments, an individual is diagnosed with hyperglycemia, prediabetes, or diabetes prior to treatment with an antagonist of IGF1R signaling. In some embodiments, administration includes intravenous injection. In some embodiments, administration includes administering about 10 mg / kg of an antagonist of IGF1R signaling over about 60 minutes to about 90 minutes based on the weight of the individual. In some embodiments, administration further includes administering about 20 mg / kg of an antagonist of IGF1R signaling over about 60 minutes to about 90 minutes based on the weight of the individual.In some embodiments, administration further comprises administering an antagonist of IGF1R signaling at about 20 mg / kg once every three weeks over about seven administrations.

[0007] In another aspect, there is provided herein a method of treating an individual afflicted with an insulin-like growth factor 1 receptor (IGF1R)-related disease, the method comprising: a) obtaining the results of a blood glucose management test from the individual; and b) administering to the individual an antagonist of IGF1R signaling if the individual exhibits normal blood glucose management as determined by the blood glucose management test. In some embodiments, the IGF1R-related disease includes thyroid ophthalmopathy. In some embodiments, the antagonist of IGF1R signaling includes an antibody that binds to IGF1R. In some embodiments, the antibody that binds to IGF1R includes ganitumab, figitumumab, MEDI-573, cixutumumab, daratumumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumumab, 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 the amino acid sequence set forth in SEQ ID NO: 5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 8; (ii) a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 9; and (iii) a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence set forth in 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 with 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 with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO: 3; and b) a light chain variable domain comprising the amino acid sequence set forth in 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 with SEQ ID NO: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity with SEQ ID NO: 2. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 1; and b) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 2.

[0008] In some embodiments, the blood glucose management test includes measurement of hemoglobin A1c (HbA1c), an oral glucose tolerance test, measurement of fasting blood glucose, measurement of non-fasting blood glucose, or any combination thereof. In some embodiments, the blood glucose management test includes measurement of hemoglobin A1c (HbA1c). In some embodiments, an individual exhibits normal blood glucose management if the measurement of HbA1c is less than about 6.5%. In some embodiments, an individual exhibits normal blood glucose management if the measurement of HbA1c is less than about 5.7%. In some embodiments, the blood glucose management test includes an oral glucose tolerance test. In some embodiments, an individual exhibits normal blood glucose management if the individual exhibits a blood glucose level of less than about 200 mg / dL at about 2 hours after oral ingestion of about 75 grams of sugar. In some embodiments, an individual exhibits normal blood glucose management if the individual exhibits a blood glucose level of about 140 mg / dL or less at about 2 hours after oral ingestion of about 75 grams of sugar. In some embodiments, the blood glucose management test includes measurement of fasting blood glucose. In some embodiments, an individual exhibits normal blood glucose management if the individual exhibits a blood glucose level of less than about 126 mg / dL after an overnight fast. In some embodiments, an individual exhibits normal blood glucose management if the individual exhibits a blood glucose level of about 99 mg / dL or less after an overnight fast. In some embodiments, the overnight fast lasts at least about 8 hours. In some embodiments, the overnight fast lasts from about 8 to about 16 hours. In some embodiments, the blood glucose management test includes measurement of non-fasting blood glucose. In some embodiments, an individual exhibits normal blood glucose management if the individual exhibits a non-fasting blood glucose level of less than about 200 mg / dL. In some embodiments, an individual is diagnosed with hyperglycemia, prediabetes, or diabetes prior to treatment with an antagonist of IGF1R signaling. In some embodiments, administration includes intravenous injection. In some embodiments, administration includes administering about 10 mg / kg of an antagonist of IGF1R signaling over about 60 to about 90 minutes based on the weight of the individual. In some embodiments, administration further includes administering about 20 mg / kg of an antagonist of IGF1R signaling over about 60 to about 90 minutes based on the weight of the individual.In some embodiments, administration further comprises administering an antagonist of IGF1R signaling at about 20 mg / kg once every three weeks over about seven administrations.

[0009] In another aspect, provided herein is a method of monitoring an individual afflicted with an IGF1R-related disease being treated with an antagonist of insulin-like growth factor 1 receptor (IGF1R) signaling, the method comprising: a) obtaining the results of a blood glucose management test from an individual being treated with an antagonist of IGF1R signaling; and b) interrupting treatment of the individual with the antagonist of IGF1R signaling if the individual exhibits abnormal blood glucose management as determined by the blood glucose management test. In some embodiments, the IGF1R-related disease includes Graves' ophthalmopathy. 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, siltuximab, daratumumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumab, or linsitinib. In some embodiments, the antibody that binds to 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 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.In some embodiments, an 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 set forth in SEQ ID NO: 5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 8; (ii) a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 9; and (iii) a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 10. In some embodiments, an 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 with 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 with SEQ ID NO: 4. In some embodiments, an antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO: 3; and b) a light chain variable domain comprising the amino acid sequence set forth in SEQ ID NO: 4. In some embodiments, an antibody that binds to IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity with SEQ ID NO: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity with SEQ ID NO: 2. In some embodiments, an antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 1; and b) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 2.

[0010] In some embodiments, the blood glucose management 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, the blood glucose management test includes the measurement of hemoglobin A1c (HbA1c). In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is about 6.5% or higher. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is about 5.7% or higher. In some embodiments, the blood glucose management test includes an oral glucose tolerance test. In some embodiments, an individual exhibits abnormal blood glucose management if the individual exhibits a blood glucose level of at least about 200 mg / dL at about 2 hours after oral ingestion of about 75 grams of sugar. In some embodiments, an individual exhibits abnormal blood glucose management if the individual exhibits a blood glucose level exceeding about 140 mg / dL at about 2 hours after oral ingestion of about 75 grams of sugar. In some embodiments, the blood glucose management test includes the measurement of fasting blood glucose. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of fasting blood glucose is about 126 mg / dL or higher after an overnight fast. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of fasting blood glucose exceeds about 99 mg / dL after an overnight fast. In some embodiments, the overnight fast lasts for at least about 8 hours. In some embodiments, the overnight fast lasts from about 8 to about 16 hours. In some embodiments, the blood glucose management test includes the measurement of non-fasting blood glucose. In some embodiments, an individual exhibits abnormal blood glucose management if the individual exhibits a non-fasting blood glucose level of about 200 mg / dL or higher. In some embodiments, an individual has been diagnosed with existing hyperglycemia, prediabetes, or diabetes prior to treatment with an antagonist of IGF1R signaling. In some embodiments, administration includes intravenous injection. In some embodiments, the method further includes obtaining the results of a second blood glucose management test from the individual after treating the individual for abnormal blood glucose management. In some embodiments, the method further includes administering an antagonist of IGF1R signaling to the individual if the individual exhibits normal blood glucose management by the second blood glucose management test.In some embodiments, administration further comprises administering an antagonist of IGF1R signaling at about 10 mg / kg based on the body weight of the individual. In some embodiments, administration further comprises administering an antagonist of IGF1R signaling at about 20 mg / kg based on the body weight of the individual once every three weeks over about seven times.

[0011] In another aspect, a method of treating an individual afflicted with an insulin-like growth factor 1 receptor (IGF1R)-related disease, comprising: a) administering to the individual a first dose of an antagonist of IGF1R signaling; b) obtaining from the individual the results of a blood glucose management test; and c) if the individual exhibits abnormal blood glucose management as determined by the blood glucose management test, administering to the individual a second dose of an antagonist of IGF1R signaling, wherein the second dose is lower than the first dose, is provided herein. In some embodiments, the IGF1R-related disease includes thyroid ophthalmopathy. In some embodiments, the antagonist of IGF1R signaling includes an antibody that binds to IGF1R. In some embodiments, the antibody that binds to IGF1R includes ganitumab, figitumumab, MEDI-573, cixutumumab, daratumumab, 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 the amino acid sequence represented by SEQ ID NO: 5; (ii) a second heavy chain complementarity-determining region (HCDR2) comprising the amino acid sequence represented by SEQ ID NO: 6; and (iii) a third heavy chain complementarity-determining region (HCDR3) comprising the amino acid sequence represented by SEQ ID NO: 7; and b) a light chain comprising: (i) a first light chain complementarity-determining region (LCDR1) comprising the amino acid sequence represented by SEQ ID NO: 8; (ii) a second light chain complementarity-determining region (LCDR2) comprising the amino acid sequence represented by SEQ ID NO: 9; and (iii) a third light chain complementarity-determining region (LCDR3) comprising the amino acid sequence represented by 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 with 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 with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising the amino acid sequence represented by SEQ ID NO: 3; and b) a light chain variable domain comprising the amino acid sequence represented by 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 with SEQ ID NO: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity with SEQ ID NO: 2. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence represented by SEQ ID NO: 1; and b) a light chain comprising the amino acid sequence represented by SEQ ID NO: 2.

[0012] In some embodiments, the blood glucose management 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, the blood glucose management test includes the measurement of hemoglobin A1c (HbA1c). In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is about 6.5% or more. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is about 5.7% or more. In some embodiments, the blood glucose management test includes an oral glucose tolerance test. In some embodiments, an individual exhibits abnormal blood glucose management if the individual exhibits a blood glucose level of about 200 mg / dL or more about 2 hours after oral ingestion of about 75 grams of sugar. In some embodiments, an individual exhibits abnormal blood glucose management if the individual exhibits a blood glucose level exceeding about 140 mg / dL about 2 hours after oral ingestion of about 75 grams of sugar. In some embodiments, the blood glucose management test includes the measurement of fasting blood glucose. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of fasting blood glucose is about 126 mg / dL or more after an overnight fast. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of fasting blood glucose exceeds about 99 mg / dL after an overnight fast. In some embodiments, the overnight fast lasts at least about 8 hours. In some embodiments, the overnight fast lasts from about 8 to about 16 hours. In some embodiments, the blood glucose management test includes the measurement of non-fasting blood glucose. In some embodiments, an individual exhibits abnormal blood glucose management if the individual exhibits a non-fasting blood glucose level of about 200 mg / dL or more. In some embodiments, an individual has been diagnosed with existing hyperglycemia, prediabetes, or diabetes prior to treatment with an antagonist of IGF1R signaling. In some embodiments, administration includes intravenous injection. In some embodiments, the first dose includes about 10 mg / kg of an antagonist of IGF1R signaling administered over about 60 to about 90 minutes based on the weight of the individual. In some embodiments, the first dose further includes about 20 mg / kg of an antagonist of IGF1R signaling administered over about 60 to about 90 minutes based on the weight of the individual.In some embodiments, an antagonist of IGF1R signaling at about 20 mg / kg is administered to an individual once every three weeks for about seven times.

[0013] In another aspect, a method of treating an individual suffering from an insulin-like growth factor 1 receptor (IGF1R)-related disease, comprising: a) selecting an individual suffering from an IGF1R-related disease for treatment with an antagonist of IGF1R signaling if the individual shows normal blood glucose management by a first test of blood glucose management; b) administering a first dose of an antagonist of IGF1R signaling to the individual; and c) obtaining the results of a second test of blood glucose management from the individual being treated with the antagonist of IGF1R signaling, is provided herein. In some embodiments, the method further comprises interrupting the treatment of the individual with the antagonist of IGF1R signaling if the individual shows abnormal blood glucose management based on the results of the second test of blood glucose management. In some embodiments, the method further comprises administering a second dose of an antagonist of IGF1R signaling to the individual if the individual shows abnormal blood glucose management based on the results of the second test of blood glucose management. In some embodiments, the IGF1R-related disease includes thyroid ophthalmopathy. 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, daratumumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumumab, or linsitinib. In some embodiments, the antibody that binds to 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 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.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 the amino acid sequence set forth in SEQ ID NO: 5; (ii) a second heavy chain complementarity-determining region (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 6; and (iii) a third heavy chain complementarity-determining region (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 7; and b) a light chain comprising: (i) a first light chain complementarity-determining region (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 8; (ii) a second light chain complementarity-determining region (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 9; and (iii) a third light chain complementarity-determining region (LCDR3) comprising the amino acid sequence set forth in 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 with 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 with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising the amino acid sequence set forth in SEQ ID NO: 3; and b) a light chain variable domain comprising the amino acid sequence set forth in 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 with SEQ ID NO: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity with SEQ ID NO: 2. In some embodiments, the antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 1; and b) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 2.

[0014] In some embodiments, the first or second test for blood glucose management includes measurement of hemoglobin A1c (HbA1c), an oral glucose tolerance test, measurement of fasting blood glucose, measurement of non-fasting blood glucose, or any combination thereof. In some embodiments, the first or second test for blood glucose management includes measurement of hemoglobin A1c (HbA1c). In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is about 6.5% or more, and an individual exhibits normal blood glucose management if the measurement of hemoglobin A1c (HbA1c) is less than about 6.5%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is about 5.7% or more, and an individual exhibits normal blood glucose management if the measurement of hemoglobin A1c (HbA1c) is less than about 5.7%. In some embodiments, the test for blood glucose management includes an oral glucose tolerance test. In some embodiments, an individual exhibits abnormal blood glucose management if the individual shows a blood glucose level of at least about 200 mg / dL about 2 hours after oral ingestion of about 75 grams of sugar, and an individual exhibits normal blood glucose management if the individual shows a blood glucose level of less than about 200 mg / dL about 2 hours after oral ingestion of about 75 grams of sugar. In some embodiments, an individual exhibits abnormal blood glucose management if the individual shows a blood glucose level exceeding about 140 mg / dL about 2 hours after oral ingestion of 75 grams of sugar, and an individual exhibits normal blood glucose management if the individual shows a blood glucose level of about 140 mg / dL or less about 2 hours after oral ingestion of about 75 grams of sugar. In some embodiments, the test for blood glucose management includes measurement of fasting blood glucose. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of fasting blood glucose is about 126 mg / dL or more after an overnight fast, and an individual exhibits normal blood glucose management if the individual shows a blood glucose level of less than about 126 mg / dL after an overnight fast. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of fasting blood glucose exceeds about 99 mg / dL after an overnight fast, and an individual exhibits normal blood glucose management if the individual shows a blood glucose level of about 99 mg / dL or less after an overnight fast. In some embodiments, the overnight fast lasts at least about 8 hours. In some embodiments, the overnight fast lasts from about 8 to about 16 hours. In some embodiments, the test for blood glucose management includes measurement of non-fasting blood glucose.In some embodiments, when an individual exhibits a non-fasting blood glucose level of about 200 mg / dL or higher, the individual exhibits abnormal blood glucose management, and when the individual exhibits a non-fasting blood glucose level of less than about 200 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, the individual has been diagnosed with existing hyperglycemia, prediabetes, or diabetes prior to treatment with an antagonist of IGF1R signaling. In some embodiments, administration includes intravenous injection. In some embodiments, the first dose comprises about 10 mg / kg of an antagonist of IGF1R signaling administered over about 60 to about 90 minutes based on the weight of the individual. In some embodiments, the first dose further comprises about 20 mg / kg of an antagonist of IGF1R signaling administered over about 60 to about 90 minutes based on the weight of the individual. In some embodiments, about 20 mg / kg of an antagonist of IGF1R signaling is administered to the individual once every three weeks for seven times. In some embodiments, the method further comprises treating the individual for abnormal blood glucose management when the individual exhibits abnormal blood glucose management based on the results of a second test of blood glucose management.

[0015] In one aspect, there is provided a method of treating an individual suffering from an insulin-like growth factor 1 receptor (IGF1R)-related disease, the method comprising: a) obtaining the results of a blood glucose test from the individual; and b) administering to the individual a dose of an antagonist of IGF1R signaling if the individual does not exhibit hyperglycemia as determined by the blood glucose test. In certain embodiments, the IGF1R-related disease includes thyroid ophthalmopathy. In certain embodiments, the antagonist of IGF1R signaling includes an antibody that binds to IGF1R. In certain embodiments, the antibody that binds to IGF1R includes ganitumab, figitumumab, MEDI-573, cixutumumab, daratumumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumumab, or linsitinib. In certain embodiments, the antibody that binds to IGF1R includes teprotumumab. In certain embodiments, the antagonist of IGF1R signaling includes 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 includes: a) a heavy chain comprising: (i) a first heavy chain complementarity determining region (HCDR1) comprising the amino acid sequence represented by SEQ ID NO: 5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence represented by SEQ ID NO: 6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence represented by SEQ ID NO: 7; and b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence represented by SEQ ID NO: 8; (ii) a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence represented by SEQ ID NO: 9; and (iii) a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence represented by SEQ ID NO: 10.In certain embodiments, an 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 with 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 with SEQ ID NO: 4. In certain embodiments, an antibody that binds to IGF1R comprises: a) a heavy chain variable domain comprising the amino acid sequence represented by SEQ ID NO: 3; and b) a light chain variable domain comprising the amino acid sequence represented by SEQ ID NO: 4. In certain embodiments, an antibody that binds to IGF1R comprises: a) a heavy chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity with SEQ ID NO: 1; and b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity with SEQ ID NO: 2. In certain embodiments, an antibody that binds to IGF1R comprises: a) a heavy chain comprising the amino acid sequence represented by SEQ ID NO: 1; and b) a light chain comprising the amino acid sequence represented by SEQ ID NO: 2. In certain embodiments, a blood glucose test comprises 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 certain embodiments, a blood glucose test comprises the measurement of hemoglobin A1c (HbA1c). In certain embodiments, an individual does not exhibit hyperglycemia when the measurement of HbA1c is about 6.5% or less. In certain embodiments, an individual does not exhibit hyperglycemia when the measurement of HbA1c is about 5.7% or less. In certain embodiments, a blood glucose test comprises an oral glucose tolerance test. In certain embodiments, an individual does not exhibit hyperglycemia when the individual exhibits a blood glucose level of less than 200 mg / dL about 2 hours after an oral ingestion of about 75 grams of sugar. In certain embodiments, an individual does not exhibit hyperglycemia when the individual exhibits a blood glucose level of less than 140 mg / dL about 2 hours after an oral ingestion of about 75 grams of sugar. In certain embodiments, a blood glucose test comprises the measurement of fasting blood glucose. In certain embodiments, an individual does not exhibit hyperglycemia when the measurement of fasting blood glucose is less than 126 mg / dL after an overnight fast. In certain embodiments, an individual does not exhibit hyperglycemia when the measurement of fasting blood glucose is less than 99 mg / dL after an overnight fast. In certain embodiments, an overnight fast lasts for at least about 8 hours. In certain embodiments, an overnight fast lasts from about 8 to about 16 hours.In certain embodiments, the blood glucose test includes measurement of non-fasting blood glucose. In certain embodiments, if an individual exhibits a non-fasting blood glucose value of less than about 200 mg / dL, the individual does not exhibit hyperglycemia. In certain embodiments, the individual has been diagnosed with existing hyperglycemia, prediabetes, or diabetes prior to treatment with an antagonist of IGF1R signaling. In certain embodiments, administration includes intravenous injection. In certain embodiments, the dose includes about 10 mg / kg of an antagonist of IGF1R signaling administered over about 60 to about 90 minutes based on the weight of the individual. In certain embodiments, the dose includes about 20 mg / kg of an antagonist of IGF1R signaling administered over about 60 to about 90 minutes based on the weight of the individual. In certain embodiments, about 20 mg / kg of an antagonist of IGF1R signaling is administered to the individual once every three weeks over about 7 times.

[0016] In another aspect, there is provided a method of treating an individual suffering from an insulin-like growth factor 1 receptor (IGF1R)-related disease and also suffering from diabetes, the method comprising: (a) administering one or more anti-diabetic agents to lower blood glucose levels; and (b) administering to the individual a dosage of an antagonist of IGF1R signaling. In certain embodiments, the IGF1R-related disease includes Graves' ophthalmopathy. 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 ganitumab, figitumumab, MEDI-573, siltuximab, daratumumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumumab, or linsitinib. In certain embodiments, the antibody that binds to IGF1R comprises teprotumumab. 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 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. 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 the amino acid sequence set forth in SEQ ID NO: 5; (ii) a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 6; and (iii) a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence set forth in SEQ ID NO: 7; and (b) a light chain comprising: (i) a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence set forth in SEQ ID NO: 8; (ii) a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence set forth in SEQ ID NO: 9; and (iii) a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence set forth in 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 with 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 with SEQ ID NO: 4. In certain embodiments, the antibody that binds to IGF1R comprises: (a) a heavy chain variable domain comprising the amino acid sequence represented by SEQ ID NO: 3; and (b) a light chain variable domain comprising the amino acid sequence represented by 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 with SEQ ID NO: 1; and (b) a light chain comprising an amino acid sequence having at least 85%, 90%, or 95% sequence identity with SEQ ID NO: 2. The antibody that binds to IGF1R comprises: (a) a heavy chain comprising the amino acid sequence represented by SEQ ID NO: 1; and (b) a light chain comprising the amino acid sequence represented by SEQ ID NO: 2. In certain embodiments, one or more anti-diabetic agents are selected from the group 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 determined 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, administration includes intravenous injection. In certain embodiments, the dose comprises an antagonist of IGF1R signaling at about 10 mg / kg administered over about 60 minutes to about 90 minutes based on the body weight of the individual. In certain embodiments, the dose comprises an antagonist of IGF1R signaling at about 20 mg / kg administered over about 60 minutes to about 90 minutes based on the body weight of the individual. In certain embodiments, the antagonist of IGF1R signaling at about 20 mg / kg is administered to the individual once every 3 weeks for about 7 times.

[0017] 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 reference to the following detailed description which describes exemplary embodiments in which the principles of the invention are utilized, and to the following appended drawings.

Brief Description of the Drawings

[0018]

Figure 1

Modes for Carrying Out the Invention

[0019] Unless otherwise indicated, the present disclosure uses conventional biological and medical methods, which are within the skill of the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0020] Definitions Throughout this disclosure, various embodiments are presented in a range format. It should be understood that the description in range format is for convenience and brevity only and should not be construed as a rigid limitation on the scope of any embodiment. Thus, a range description should be considered to specifically disclose all possible sub-ranges down to one-tenth of the unit of the lower limit and each individual numerical value within that range, unless specifically stated otherwise in context. For example, a range description such as 1 - 6 should be considered to specifically disclose sub-ranges such as 1 - 3, 1 - 4, 1 - 5, 2 - 4, 2 - 6, 3 - 6, and individual values within that range, such as 1.1, 2, 2.3, 5, and 5.9. This applies regardless of the width of the range. The upper and lower limits of these intervening ranges can be independently included in a smaller range and are also included in this disclosure subject to any specifically excluded limitations within the described range. Unless specifically stated otherwise in context, if the described range includes one or both of the limits, ranges excluding either or both of those included limits are also included in this disclosure. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of any embodiment. As used herein, the singular forms "a", "an", and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise. The terms "comprises" and / or "comprising", as used herein, specify the presence of the stated features, integers, steps, operations, elements, and / or components, but do not preclude 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 associated listed items.

[0021] Unless otherwise specified or clear from the context, as used herein, the term "about" in connection with a numerical value or range of numerical values means the recited numerical value and the numerical value + / - 10%, or for values listed for a range, means less than 10% below the recited lower limit and greater than 10% above the recited upper limit.

[0022] 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 are useful for treatment. 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.

[0023] The term "antibody" as used herein is used in the broadest sense and includes monoclonal antibodies and intact antibodies and functional (antigen-binding) antibody fragments thereof, including fragment antigen binding (Fab) fragments, F(ab’)2 fragments, Fab’ fragments, Fv fragments, recombinant IgG (rIgG) fragments, single-chain antibody fragments (single-chain variable fragments (sFv or scFv), and single-domain antibody (e.g., sdAb, sdFv, nanobody) fragments). The term includes immunoglobulins in genetically engineered and / or otherwise modified forms, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multispecific, e.g., bispecific, antibodies, diabodies, triabodies, and tetra-bodies, tandem diabody-scFv, tandem triabody-scFv. Unless otherwise specified, it should be understood that the term "antibody" includes its functional antibody fragments. The term also includes intact or full-length antibodies, which includes antibodies of any class or subclass, including IgG and its subclasses, IgM, IgE, IgA, and IgD. An antibody may comprise a human IgG1 constant region. An antibody may comprise a human IgG4 constant region.

[0024] The terms "complementary determining region" and "CDR", which are synonymous with "hypervariable region" or "HVR", are known in the art to refer to discontinuous sequences of amino acids within the variable region of an antibody that confer antigen specificity and / or binding affinity. Generally, 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. The terms "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. Generally, 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 exact amino acid sequence boundaries of a given CDR or FR can be readily determined using any of several well-known schemes, including those described below: Kabat et al. (1991), “Sequences of Proteins of Immunological Interest”, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (the “Kabat” numbering scheme); Al-Lazikani et al., (1997) JMB 273, 927-948 (the “Chothia” numbering scheme); MacCallum et al., J. Mol. Biol. 262:732-745 (1996), “Antibody-antigen interactions: Contact analysis and binding site topography”, J. Mol. Biol. 262, 732-745”. (the “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, 2003 Jan;27(1):55-77 (the “IMGT” numbering scheme); Honegger A and Plueckthun A, “Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool”, J Mol Biol, 2001 Jun 8;309(3):657-70, (the “Aho” numbering scheme); and Whitelegg NR and Rees AR, “WAM: an improved algorithm for modelling antibodies on the WEB”, Protein Eng. 2000 Dec;13(12):819-24 (the “AbM” numbering scheme).In certain embodiments, the CDRs of the antibodies described herein can be defined by methods selected from Kabat, Chothia, IMGT, Aho, AbM, or combinations thereof.

[0025] The boundaries of a given CDR or FR can vary depending on the scheme used for identification. For example, the Kabat scheme is based on structural alignment, while the Chothia scheme is based on structural information. The numbering of both the Kabat and Chothia schemes is based on the most common antibody region sequence lengths, with insertions being accommodated by inserted letters, e.g., "30a", and deletions occurring in some antibodies. The two schemes place specific insertions and deletions ("indels") at different positions, resulting in different numberings. The Contact scheme is based on the analysis of complex crystal structures and is similar in many respects to the Chothia numbering scheme.

[0026] The term "variable region" or "variable domain" refers to the domain of an antibody heavy or light chain that is involved in binding of the antibody to an antigen. The variable domains of the heavy and light chains of a natural antibody (V H and V L ), respectively) generally have similar structures, and each domain contains four conserved framework regions (FRs) and three CDRs (see, e.g., Kindt et al. Kuby Immunology, 6th ed., W.H. Freeman and Co., page 91 (2007)). A single V H or V L domain may be sufficient to confer antigen-binding specificity. Further, an antibody that binds a particular antigen can be isolated by screening a library of V H or V L domains from antibodies that bind the antigen for a complementary V L or V H domain (see, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991)).

[0027] The specific binding or association of the antibody molecules described herein refers to binding mediated by one or more CDR portions of the antibody. Not all CDRs are required for specific binding. Specific binding to a particular described target or antigen, which shows a significant increase in binding compared to an isotype control antibody, can be demonstrated, for example, by ELISA.

[0028] Among the antibodies provided are antibody fragments. An "antibody fragment" refers to a molecule other than an intact antibody that includes a portion that binds to an antigen to which the intact antibody binds in an intact antibody. 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 certain embodiments, the antibody is a single-chain antibody fragment that includes a variable heavy chain region and / or a variable light chain region, e.g., scFv.

[0029] Antibody fragments can be made by a variety of techniques including, but not limited to, proteolytic digestion of intact antibodies and production by recombinant host cells. In some embodiments, the antibody is a recombinantly produced fragment, e.g., one that includes a non-naturally occurring configuration, e.g., two or more antibody regions or chains linked by a synthetic linker, e.g., a polypeptide linker, and / or one that is not produced by enzymatic digestion of a native intact antibody. In some aspects, the antibody fragment is an scFv.

[0030] A "humanized" antibody is an antibody in which all or substantially all of the CDR amino acid residues are derived from non-human CDRs and all or substantially all of the FR amino acid residues are derived from human FRs. A humanized antibody may optionally include at least a portion of an antibody constant region derived from a human antibody. A "humanized form" of a non-human antibody refers to a variant of the non-human antibody that has been humanized to typically reduce its immunogenicity in humans while maintaining the specificity and affinity of the parental non-human antibody. In some embodiments, some FR residues in the humanized antibody are replaced with corresponding residues from a non-human antibody (e.g., the antibody from which the CDR residues are derived) in order to, for example, restore or improve antibody specificity or affinity.

[0031] Among the antibodies provided are human antibodies. A "human antibody" is an antibody having an amino acid sequence corresponding to that of an antibody produced by a human or human cell, or a non-human source using a human antibody repertoire or other human antibody coding sequences (including a human antibody library). This term excludes humanized forms of non-human antibodies that include non-human antigen-binding regions, e.g., those in which all or substantially all of the CDRs are non-human.

[0032] Human antibodies can be prepared by administering an immunogen to a transgenic animal that has been modified to produce intact human antibodies or intact antibodies having human variable regions in response to antigen administration. Such animals typically contain all or part of the human immunoglobulin locus, which replaces the endogenous immunoglobulin locus, or is present extrachromosomally or randomly integrated into the animal's chromosomes. In such transgenic animals, the endogenous immunoglobulin locus is generally inactivated. Human antibodies can also be derived from human antibody libraries including phage display and cell-free libraries containing antibody coding sequences derived from the human repertoire.

[0033] The terms "polypeptide" and "protein" are used interchangeably to refer to polymers of amino acid residues and are not limited to a minimum length. The polypeptides provided, including the antibodies and antibody chains and other peptides, such as linkers and binding peptides, can include amino acid residues that contain natural and / or non-natural amino acid residues. These terms also include post-expression modifications of the polypeptide, such as glycosylation, sialylation, acetylation, phosphorylation, and the like. In some embodiments, a polypeptide can contain modifications to the native or natural sequence as long as the protein maintains the desired activity. These modifications can be intentional, such as by site-directed mutagenesis, or can be accidental, such as by mutations in the host producing the protein or errors in PCR amplification.

[0034] In some embodiments, amino acid sequence variants of the antibodies provided herein are contemplated. Variants typically differ from the polypeptides specifically disclosed herein by one or more substitutions, deletions, additions, and / or insertions. Such variants can be natural or can be generated synthetically, for example, by modifying one or more of the above polypeptide sequences of the invention, assessing one or more biological activities of the polypeptides described herein, and / or using any of several known techniques. For example, it may be desirable to improve the binding affinity and / or other biological properties of the antibody. Amino acid sequence variants of the antibody can be prepared by introducing appropriate modifications into the nucleotide sequence encoding the antibody or by peptide synthesis. Such modifications include, for example, deletions from residues within the amino acid sequence of the antibody and / or insertions and / or substitutions of such residues. Any combination of deletions, insertions, and substitutions can be made to arrive at the final construct, provided that the final construct has the desired properties, such as antigen binding.

[0035] The percent sequence identity to a reference polypeptide sequence is the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and without considering conservative substitutions as part of sequence identity. Alignments for the purpose of determining amino acid sequence identity percent can be achieved by various methods known in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Appropriate parameters for aligning the sequences can be determined that include an algorithm necessary to achieve the maximum alignment over the entire length of the sequences being compared. However, for the purposes of this specification, the amino acid sequence identity % value is generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was created by Genentech, Inc., and the source code was submitted with user documentation at the U.S. Copyright Office, Washington D.C., 20559 (where it is registered under U.S. Copyright Registration No. TXU510087). The ALIGN-2 program is publicly available from Genentech, Inc. (South San Francisco, Calif.) or can be compiled from the source code. The ALIGN-2 program should be compiled for use in a UNIX operating system including Digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary.

[0036] In situations where ALIGN-2 is used for amino acid sequence comparison, the percent amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be expressed as a given amino acid sequence A having or containing a particular % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 × fraction X / Y, where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in the alignment of the programs of A and B, and Y is the total number of amino acid residues in B. It will be understood that the length of amino acid sequence A is not equal to the length of amino acid sequence B and that the percent amino acid sequence identity of A to B is not equal to the percent amino acid sequence identity of B to A. Unless otherwise specified, all values of percent amino acid sequence identity used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program.

[0037] As described herein, a "blood glucose management test" is any test capable of accurately measuring blood glucose in an individual. Such tests can use personal blood glucose monitors, e.g., those corresponding to diabetes test strips or insulin pumps; continuous blood glucose monitors, as well as experimental blood glucose analyzers and automated analyzers used by hospitals and contract laboratories. Such tests for blood glucose management include, but are not limited to, measurement of fasting blood glucose, non-fasting blood glucose, oral glucose tolerance test, or measurement of glycated hemoglobin A1c (HbA1c).

[0038] As used herein, "treating," "treatment," or "to treat" refers to an intentional intervention on a physiological condition that, for example, results in a reduction in the severity of a disease or medical condition; a reduction in the period of the course of the medical condition; an improvement or elimination of one or more symptoms associated with the disease or medical condition; or the provision of a beneficial effect to a subject having the disease or medical condition. Treatment does not require the cure of an underlying disease or underlying condition. As used herein with respect to thyroid eye disease, treatment can result in a decrease in the Clinical Activity Score (CAS). This decrease can be by 1, 2, 3, 4, 5, 6, or more points.

[0039] Normal glycemic control, when absent, can be achieved by any suitable 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 glucose can be determined by a physician or patient self-administration of insulin prior to administration of an IGF1R inhibitor.

[0040] A "therapeutically effective amount," "effective dose," "effective amount," or "therapeutically effective dosage" of a drug or therapeutic agent, when used alone or in combination with another therapeutic agent, is any amount of the drug that protects a subject from the onset of a disease or promotes regression of the disease as evidenced by a decrease in the severity of the disease symptoms, an increase in the frequency and duration of periods without disease symptoms, or prevention of a disorder or physical impairment caused by the disease. The ability of a therapeutic agent to promote regression of a disease can be evaluated using various methods known to those of skill in the art, for example, in human subjects during clinical trials, in animal model systems that predict efficacy in humans, or in in vitro assays that evaluate the activity of the agent.

[0041] As used herein, "pharmaceutically acceptable" in relation to "carrier", "excipient" or "diluent" includes any physiologically compatible solvent, dispersion medium, coating, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like. In some embodiments, the carrier is suitable for intravenous, intramuscular, subcutaneous, parenteral, intraspinal or topical administration (e.g., by injection or infusion). Depending on the route of administration, the active compound, i.e., the antibody, may be coated with a material to protect the compound from the action of acids and other natural conditions that may inactivate the compound.

[0042] Methods and Compositions for the Treatment of IGF1R-Related Diseases Insulin-like growth factor 1 receptor (IGF1R) is expressed on the surface of several cell types. IGF1R belongs to the insulin receptor family and has tyrosine kinase activity. IGF1R signaling is involved in diseases including thyroid eye disease (TED), also known as Graves ophthalmopathy, Graves' eye disease, Graves' orbitopathy, and thyroid-associated ophthalmopathy (TAO). Thyroid eye disease is an autoimmune disease that can cause inflammation and damage to the eye muscles and connective tissues. Symptoms of thyroid eye disease can include eye swelling, orbital deformation, vision loss, and blindness. IGF1R-related diseases can be treated with antagonists of IGF1R signaling.

[0043] Thyroid eye disease can be evaluated by the Clinical Activity Score (CAS) described by Mourits et al., British Journal of Ophthalmology, 1989, 73, no. 8, 639-644, as a method for assessing the degree of active disease. This score was proposed as a clinical classification for easily differentiating active disease from inactive disease based on the classical signs of acute inflammation (pain, redness, swelling, and dysfunction), and was revised in 1997 (Mourits et al., Clinical Endocrinology, 1997, 47, no. 1, 9-14). The CAS consists of the following seven components: spontaneous retro-orbital pain, pain on attempted eye movements (upward gaze, lateral gaze, and downward gaze), conjunctival injection, eyelid injection, conjunctival edema, swelling of the caruncle / crease, and eyelid swelling. Each component is scored as present (1 point) or absent (0 points). The score in each efficacy assessment is the sum of all present items, giving a range of 0-7, where 0 or 1 constitutes inactive disease and 7 constitutes severe active ophthalmopathy. The CAS score can distinguish between active TED and inactive TED. The quality of life of an individual can be measured using a self-assessment questionnaire such as the Graves' ophthalmopathy quality of life (GO-QoL) questionnaire. See, for example, Terwee CB, Gerding MN, Dekker FW, Prummel MF, Wiersinga WM. Development of a disease specific quality of life questionnaire for patients with Graves’ ophthalmopathy: the GO-QoL. Br J Cancer. 1998 Jul;82(7):773-9.

[0044] Also, in certain embodiments where an individual is selected for treatment based on the CAS, individuals with a lower CAS may delay treatment. In certain embodiments, individuals with a CAS of 3 or less, 2 or less, 1 or less, or 0 may delay treatment until normal blood glucose is established. Individuals with inactive or non-inflammatory TED may delay treatment until normal blood glucose management is established.

[0045] In one aspect, methods are provided herein for the diagnosis, treatment, or monitoring of an individual afflicted with an insulin-like growth factor 1 receptor (IGF1R)-related disease. In some embodiments, the method comprises one or more steps disclosed herein. In some embodiments, the method comprises one or more, but not all, of the steps disclosed herein. FIG. 1 is an illustration of one embodiment of method 100. The processes, steps, compositions, and components of method 100 are for illustration purposes only and should in no way be construed as limiting the scope of the methods disclosed herein.

[0046] In some embodiments, the method comprises step 102 of obtaining the results of a first test of glycemic control from an individual afflicted with an IGF1R-related disease. In some embodiments, the method comprises step 104 of selecting an individual afflicted with an IGF1R-related disease for treatment with an antagonist of IGF1R signaling. In some embodiments, the method comprises selecting an individual afflicted with an IGF1R-related disease for treatment with an antagonist of IGF1R signaling based on the results of a first test of glycemic control. In some embodiments, the method comprises selecting an individual afflicted with an IGF1R-related disease for treatment with an antagonist of IGF1R signaling if the individual exhibits normal glycemic control in a first test of glycemic control. In some embodiments, the method comprises selecting an individual afflicted with an IGF1R-related disease for treatment with an antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control in a first test of glycemic control. In some embodiments, the method comprises treating the individual for abnormal glycemic control prior to selecting an individual afflicted with an IGF1R-related disease for treatment with an antagonist of IGF1R signaling. In some embodiments, treatment of abnormal glycemic control includes any suitable treatment including, but not limited to, insulin therapy.

[0047] In some embodiments, the method includes step 106 of administering to the individual an antagonist of IGF1R signaling at a first dose. In some embodiments, the method includes administering to the individual an antagonist of IGF1R signaling at a first dose based on the results of a first test of glycemic management. In some embodiments, the method includes administering to the individual an antagonist of IGF1R signaling at a first dose if the individual exhibits normal glycemic management in a first test of glycemic management. In some embodiments, the method includes administering to the individual an antagonist of IGF1R signaling at a first dose if the individual exhibits abnormal glycemic management in a first test of glycemic management. In some embodiments, the method includes treating the individual for abnormal glycemic management prior to administering to the individual an antagonist of IGF1R signaling at a first dose.

[0048] In some embodiments, the method includes step 108 of obtaining the results of a second test of glycemic management from an individual being treated with an antagonist of IGF1R signaling at a first dose. In some embodiments, the method includes step 110 of interrupting the treatment of the individual with an antagonist of IGF1R signaling at a first dose. In some embodiments, the method includes interrupting the treatment of the individual with an antagonist of IGF1R signaling at a first dose based on the results of a second test of glycemic management. In some embodiments, the method includes interrupting the treatment of the individual with an antagonist of IGF1R signaling at a first dose if the individual exhibits abnormal glycemic management in a second test of glycemic management. In some embodiments, the method includes interrupting the treatment of the individual with an antagonist of IGF1R signaling at a first dose if the individual exhibits normal glycemic management in a second test of glycemic management.

[0049] In some embodiments, the method includes step 112 of administering to the individual a second dose of an antagonist of IGF1R signaling. In some embodiments, the method includes administering to the individual a second dose of an antagonist of IGF1R signaling based on the results of a second test of glycemic control. In some embodiments, the method includes administering to the individual a second dose of an antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control as determined by a second test of glycemic control. In some embodiments, the method includes administering to the individual a second dose of an antagonist of IGF1R signaling if the individual exhibits normal glycemic control as determined by a second test of glycemic control. 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 greater than the first dose of the antagonist of IGF1R signaling. In some embodiments, the second dose of the antagonist of IGF1R signaling is less than the first dose of the antagonist of IGF1R signaling. In some embodiments, the second test of glycemic control is a different test than the first test of glycemic control. In some embodiments, the second test of glycemic control is the same test as the first test of glycemic control. In some embodiments, the method includes step 114 of treating the individual for abnormal glycemic control if the individual exhibits abnormal glycemic control as determined by a second test of glycemic control. In some embodiments, treatment of abnormal glycemic control includes any suitable treatment including, but not limited to, insulin therapy.

[0050] In some embodiments, method 100, or one or more steps of method 100, or a process disclosed herein can 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 test of glycemic control from an individual suffering from an IGF1R-related disease. In some embodiments, the method comprises selecting an individual suffering from an IGF1R-related disease for treatment with a pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the method comprises selecting an individual suffering from an IGF1R-related disease for treatment with a pharmaceutical composition comprising an antagonist of IGF1R signaling based on the results of a first test of glycemic control. In some embodiments, the method comprises selecting an individual suffering from an IGF1R-related disease for treatment with a pharmaceutical composition comprising an antagonist of IGF1R signaling if the individual demonstrates normal glycemic control by a first test of glycemic control. In some embodiments, the method comprises selecting an individual suffering from an IGF1R-related disease for treatment with a pharmaceutical composition comprising an antagonist of IGF1R signaling if the individual demonstrates abnormal glycemic control by a first test of glycemic control. In some embodiments, the method comprises treating the individual for abnormal glycemic control prior to selecting an individual suffering from an IGF1R-related disease for treatment with a pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, treatment of abnormal glycemic control includes any suitable treatment including, but not limited to, insulin therapy.

[0051] In some embodiments, the method includes administering to an individual a pharmaceutical composition comprising an antagonist of IGF1R signaling at a first dose. In some embodiments, the method includes administering to an individual a pharmaceutical composition comprising an antagonist of IGF1R signaling at a first dose based on the results of a first test of glycemic control. In some embodiments, the method includes administering to an individual a pharmaceutical composition comprising an antagonist of IGF1R signaling at a first dose if the individual exhibits normal glycemic control by a first test of glycemic control. In some embodiments, the method includes administering to an individual a pharmaceutical composition comprising an antagonist of IGF1R signaling at a first dose if the individual exhibits abnormal glycemic control by a first test of glycemic control. In some embodiments, the method includes treating the individual for abnormal glycemic control prior to administering to the individual a pharmaceutical composition comprising an antagonist of IGF1R signaling at a first dose.

[0052] In some embodiments, the method includes obtaining the results of a second test of glycemic control from an individual being treated with a pharmaceutical composition comprising an antagonist of IGF1R signaling at a first dose. In some embodiments, the method includes interrupting treatment of the individual with a pharmaceutical composition comprising an antagonist of IGF1R signaling at a first dose. In some embodiments, the method includes interrupting treatment of the individual with a pharmaceutical composition comprising an antagonist of IGF1R signaling at a first dose based on the results of a second test of glycemic control. In some embodiments, the method includes interrupting treatment of the individual with a pharmaceutical composition comprising an antagonist of IGF1R signaling at a first dose if the individual exhibits abnormal glycemic control by a second test of glycemic control. In some embodiments, the method includes interrupting treatment of the individual with a pharmaceutical composition comprising an antagonist of IGF1R signaling at a first dose if the individual exhibits normal glycemic control by a second test of glycemic control.

[0053] In some embodiments, the method comprises administering to the individual a pharmaceutical composition comprising a second dose of an antagonist of IGF1R signaling. In some embodiments, the method comprises administering to the individual a pharmaceutical composition comprising a second dose of an antagonist of IGF1R signaling based on the results of a second test of glycemic control. In some embodiments, the method comprises administering to the individual a pharmaceutical composition comprising a second dose of an antagonist of IGF1R signaling if the individual exhibits abnormal glycemic control as determined by a second test of glycemic control. In some embodiments, the method comprises administering to the individual a pharmaceutical composition comprising a second dose of an antagonist of IGF1R signaling if the individual exhibits normal glycemic control as determined by a second test of glycemic control. 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 greater 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 less than the first dose of the pharmaceutical composition comprising an antagonist of IGF1R signaling. In some embodiments, the second test of glycemic control is a different test than the first test of glycemic control. In some embodiments, the second test of glycemic control is the same test as the first test of glycemic control. In some embodiments, the method comprises treating the individual for abnormal glycemic control if the individual exhibits abnormal glycemic control as determined by a second test of glycemic control. In some embodiments, treatment of abnormal glycemic control includes any suitable treatment including, but not limited to, insulin therapy.

[0054] In some embodiments, the IGF1R-related disease includes 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, an antagonist of IGF1R signaling inhibits, reduces, blocks, or prevents IGF1R signaling. In some embodiments, an antagonist of IGF1R signaling includes an antibody that binds to IGF1R. In some embodiments, the binding of an antagonist of IGF1R signaling to IGF1R inhibits, reduces, blocks, or prevents IGF1R signaling. In some embodiments, the antibody that binds to IGF1R includes one or more selected from the group consisting of ganitumab, figitumumab, MEDI-573, siltuximab, daratumumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumumab, linsitinib, and teprotumumab. In some embodiments, the antibody that binds to IGF1R includes two selected from the group consisting of ganitumab, figitumumab, MEDI-573, siltuximab, daratumumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumumab, linsitinib, and teprotumumab. In some embodiments, the antibody that binds to IGF1R includes three selected from the group consisting of ganitumab, figitumumab, MEDI-573, siltuximab, daratumumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumumab, linsitinib, and teprotumumab. In some embodiments, the antibody that binds to IGF1R includes four or more selected from the group consisting of ganitumab, figitumumab, MEDI-573, siltuximab, daratumumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumumab, linsitinib, and teprotumumab. In some embodiments, the antibody that binds to IGF1R includes teprotumumab, also known as TEPEZZA® (teprotumumab-trbw). In some embodiments, an antagonist of IGF1R signaling includes a small molecule that inhibits, reduces, blocks, or prevents IGF1R signaling.In some embodiments, the small molecule comprises 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 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 three 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 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.

[0055] In some embodiments, antagonists of IGF1R signaling include: (a) antibodies that bind to IGF1R; and (b) small molecules that inhibit, reduce, block, or prevent IGF1R signaling. In some embodiments, antagonists of IGF1R signaling include: (a) an antibody that binds to IGF1R, comprising one or more selected from the group consisting of ganitumab, figitumumab, MEDI-573, siltuximab, daratumumab, robatumumab, AVE1642, BIIB022, xentuzumab, istiratumab, linsitinib, and teprotumumab; and (b) a small molecule that inhibits, reduces, blocks, or prevents IGF1R signaling, comprising 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, antagonists of IGF1R signaling include: (a) an antibody that binds to IGF1R, comprising teprotumumab; and (b) a small molecule that inhibits, reduces, blocks, or prevents IGF1R signaling, comprising 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.

[0056] In some embodiments, the antibody that binds to IGF1R comprises an amino acid sequence represented by any one listed in Table 1.

[0057]

Table 1-1

[0058] In some embodiments, the antibody that binds to IGF1R comprises a heavy chain that comprises a first heavy chain complementarity determining region (HCDR1) comprising the amino acid sequence represented by SEQ ID NO: 5. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain that comprises a second heavy chain complementarity determining region (HCDR2) comprising the amino acid sequence represented by SEQ ID NO: 6. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain that comprises a third heavy chain complementarity determining region (HCDR3) comprising the amino acid sequence represented by SEQ ID NO: 7. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising: (a) an HCDR1 comprising the amino acid sequence represented by SEQ ID NO: 5; (b) an HCDR2 comprising the amino acid sequence represented by SEQ ID NO: 6; and (c) an HCDR3 comprising the amino acid sequence represented by SEQ ID NO: 7. In some embodiments, the antibody that binds to IGF1R comprises a light chain that comprises a first light chain complementarity determining region (LCDR1) comprising the amino acid sequence represented by SEQ ID NO: 8. In some embodiments, the antibody that binds to IGF1R comprises a light chain that comprises a second light chain complementarity determining region (LCDR2) comprising the amino acid sequence represented by SEQ ID NO: 9. In some embodiments, the antibody that binds to IGF1R comprises a light chain that comprises a third light chain complementarity determining region (LCDR3) comprising the amino acid sequence represented by SEQ ID NO: 10. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising: (a) an LCDR1 comprising the amino acid sequence represented by SEQ ID NO: 8; (b) an LCDR2 comprising the amino acid sequence represented by SEQ ID NO: 9; and (c) an LCDR3 comprising the amino acid sequence represented by SEQ ID NO: 10. In some embodiments, the antibody that binds to IGF1R comprises: (a) a heavy chain comprising: (i) an HCDR1 comprising the amino acid sequence represented by SEQ ID NO: 5; (ii) an HCDR2 comprising the amino acid sequence represented by SEQ ID NO: 6; and (iii) an HCDR3 comprising the amino acid sequence represented by SEQ ID NO: 7; and (b) a light chain comprising: (i) an LCDR1 comprising the amino acid sequence represented by SEQ ID NO: 8; (ii) an LCDR2 comprising the amino acid sequence represented by SEQ ID NO: 9; and (iii) an LCDR3 comprising the amino acid sequence represented by SEQ ID NO: 10.

[0059] In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) comprising an amino acid sequence having at least 75% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) comprising an amino acid sequence having at least 76% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) comprising an amino acid sequence having at least 77% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) comprising an amino acid sequence having at least 78% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) comprising an amino acid sequence having at least 79% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) comprising an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) comprising an amino acid sequence having at least 81% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) comprising an amino acid sequence having at least 82% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) comprising an amino acid sequence having at least 83% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) comprising an amino acid sequence having at least 84% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V Hcomprises. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V) having an amino acid sequence with at least 86% sequence identity to SEQ ID NO: 3 H comprises. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V) having an amino acid sequence with at least 87% sequence identity to SEQ ID NO: 3 H comprises. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V) having an amino acid sequence with at least 88% sequence identity to SEQ ID NO: 3 H comprises. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V) having an amino acid sequence with at least 89% sequence identity to SEQ ID NO: 3 H comprises. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V) having an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 3 H comprises. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V) having an amino acid sequence with at least 91% sequence identity to SEQ ID NO: 3 H comprises. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V) having an amino acid sequence with at least 92% sequence identity to SEQ ID NO: 3 H comprises. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V) having an amino acid sequence with at least 93% sequence identity to SEQ ID NO: 3 H comprises. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V) having an amino acid sequence with at least 94% sequence identity to SEQ ID NO: 3 H comprises. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V) having an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 3 H comprises. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V) having an amino acid sequence with at least 96% sequence identity to SEQ ID NO: 3 Hincludes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) that includes an amino acid sequence having at least 97% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) that includes an amino acid sequence having at least 98% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) that includes an amino acid sequence having at least 99% sequence identity with SEQ ID NO: 3. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H ) that includes the amino acid sequence represented by SEQ ID NO: 3.

[0060] In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ) that includes an amino acid sequence having at least 75% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ) that includes an amino acid sequence having at least 76% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ) that includes an amino acid sequence having at least 77% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ) that includes an amino acid sequence having at least 78% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ) that includes an amino acid sequence having at least 79% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V L ) that includes an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V H) and includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 82% sequence identity to SEQ ID NO: 3 H ) and includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 83% sequence identity to SEQ ID NO: 3 H ) and includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 84% sequence identity to SEQ ID NO: 3 H ) and includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 3 H ) and includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 86% sequence identity to SEQ ID NO: 3 H ) and includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 87% sequence identity to SEQ ID NO: 3 H ) and includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 88% sequence identity to SEQ ID NO: 3 H ) and includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 89% sequence identity to SEQ ID NO: 3 H ) and includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 3 H ) and includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 91% sequence identity to SEQ ID NO: 3 H ) and includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 92% sequence identity to SEQ ID NO: 3 H) includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 93% sequence identity to SEQ ID NO: 3 H ) includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 94% sequence identity to SEQ ID NO: 3 H ) includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 3 H ) includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 96% sequence identity to SEQ ID NO: 3 H ) includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 97% sequence identity to SEQ ID NO: 3 H ) includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 98% sequence identity to SEQ ID NO: 3 H ) includes. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain variable domain (V having an amino acid sequence with at least 99% sequence identity to SEQ ID NO: 3 H ) includes. In some embodiments, the antibody that binds to IGF1R comprises a light chain variable domain (V having the amino acid sequence represented by SEQ ID NO: 4 L ) includes.

[0061] In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 75% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 75% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 76% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 76% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 77% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 77% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 78% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 78% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 79% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 79% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 81% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 81% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 82% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 82% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 83% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 83% sequence identity with SEQ ID NO: 4.In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 84% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 84% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 85% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 85% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 86% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 86% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 87% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 87% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 88% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 88% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 89% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 89% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 91% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 91% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 92% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 92% sequence identity with SEQ ID NO: 4.In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 93% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 93% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 94% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 94% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 96% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 96% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 97% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 97% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 98% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 98% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a VH comprising an amino acid sequence having at least 99% sequence identity with SEQ ID NO: 3 and a VL comprising an amino acid sequence having at least 99% sequence identity with SEQ ID NO: 4. In some embodiments, the antibody that binds to IGF1R comprises a V comprising the amino acid sequence represented by SEQ ID NO: 3. H and a V comprising the amino acid sequence represented by SEQ ID NO: 4 L comprises.

[0062] In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 75% sequence identity with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with SEQ ID NO: 1. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising the amino acid sequence represented by SEQ ID NO: 1.

[0063] In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising an amino acid sequence having at least 75% sequence identity with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with 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 with SEQ ID NO: 2. In some embodiments, the antibody that binds to IGF1R comprises a light chain comprising the amino acid sequence represented by SEQ ID NO: 2.

[0064] In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising an amino acid sequence having at least 75% sequence identity with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 75% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 76% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 77% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 78% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 79% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 80% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 81% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 82% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 83% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 84% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 85% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 86% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 87% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 88% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 89% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 90% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 91% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 92% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 93% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 94% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 95% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 96% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 97% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 98% sequence identity with 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 with SEQ ID NO: 1 and a light chain comprising an amino acid sequence having at least 99% sequence identity with SEQ ID NO: 2. In some embodiments, the antibody that binds to IGF1R comprises a heavy chain comprising the amino acid sequence represented by SEQ ID NO: 1 and a light chain comprising the amino acid sequence represented by SEQ ID NO: 2.

[0065] In some embodiments, the blood glucose management test includes a test that measures the level of glucose in a blood sample. In some embodiments, the blood glucose management test includes a test that measures the level of sugar in a blood sample. In some embodiments, when the blood glucose level is within a first range, the individual may be classified as healthy. In some embodiments, when the blood glucose level is within a second range and each value in the second range is higher than each value in the first range, the individual may be classified as having prediabetes. In some embodiments, when the blood glucose level is within a third range and each value in the third range is higher than each value in the second range, the individual may be classified as having diabetes. In some embodiments, the blood glucose management test includes any type of test that has been used, is being used, or is intended to be used for measuring the blood glucose level. In some embodiments, the blood glucose management test includes any type of test that has been used, is being used, or is intended to be used for the diagnosis of blood glucose-related diseases including, but not limited to, hyperglycemia, high blood sugar, prediabetes, diabetes, type 1 diabetes, type 2 diabetes, gestational diabetes, impaired glucose tolerance, or glucose intolerance. In some embodiments, the blood glucose management test may be performed using a blood glucose test kit, a blood glucose test device, or both. In some embodiments, the blood glucose management 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, the blood glucose management test disclosed herein is applicable to the first blood glucose management test of the method disclosed herein, the second blood glucose management test of the method disclosed herein, or both.

[0066] In some embodiments, the blood glucose management test includes measuring hemoglobin A1c (HbA1c) in a blood sample. In some embodiments, measuring hemoglobin A1c (HbA1c) in a blood sample is also known as a glycated hemoglobin test, a glycosylated hemoglobin test, a hemoglobin A1C test, or an HbA1c test. In some embodiments, the HbA1c test includes measuring glycated hemoglobin protein in a blood sample. In some embodiments, the HbA1c test includes measuring the average level of glycated hemoglobin protein in a blood sample over a period of time. In some embodiments, the HbA1c test includes measuring the average level of the percentage of glycated hemoglobin protein in the total amount of hemoglobin protein in a blood sample over a period of time. In some embodiments, the period is about 90 days. In some embodiments, the period of the HbA1c test is from about 0 to 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 period therebetween. In some embodiments, the period of the HbA1c test is from about 0 to about 24 months, from about 0 to about 12 months, from about 0 to 6 months, from about 0 to 5 months, from about 0 to 4 months, from about 0 to 3 months, from about 0 to 2 months, from about 0 to 1 month, from about 1 to 24 months, from about 1 to 12 months, from about 1 to 6 months, from about 1 to 5 months, from about 1 to 4 months, from about 1 to 3 months, from about 1 to 2 months, from about 2 to 24 months, from about 2 to 12 months, from about 2 to 6 months, from about 2 to 5 months, from about 2 to 4 months, from about 2 to 3 months, from about 3 to 24 months, from about 3 to 12 months, from about 3 to 6 months, from about 3 to 5 months, from about 3 to 4 months, from about 4 to 24 months, from about 4 to 12 months, from about 4 to 6 months, from about 4 to 5 months, from about 5 to 24 months, from about 5 to 12 months, or from about 5 to 6 months. In some embodiments, the period of the HbA1c test is about 1 month. In some embodiments, the period of the HbA1c test is about 2 months.In some embodiments, the period of the HbA1c test is about three months.

[0067] In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 4.5%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 4.6%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 4.7%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 4.8%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 4.9%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 5.0%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 5.1%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 5.2%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 5.3%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 5.4%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 5.5%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 5.6%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 5.7%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 5.8%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 5.9%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 6.0%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 6.1%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 6.2%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 6.3%. In some embodiments, an individual exhibits normal glycemic control if the measurement of HbA1c is less than about 6.4%.In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 6.5%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 6.6%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 6.7%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 6.8%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 6.9%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 7.0%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 7.1%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 7.2%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 7.3%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 7.4%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 7.5%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 7.6%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 7.7%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 7.8%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 7.9%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 8.0%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 8.5%. In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is less than about 9.0%.

[0068] In some embodiments, an individual exhibits normal blood glucose management when the measurement of HbA1c is from 0% to about 7.5%, such as 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%, about 3.9%, about 3.8%, 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.

[0069] In some embodiments, a method of treating an individual suffering from an IGF1R-related disease includes not selecting an individual suffering from an IGF1R-related disease for treatment with an antagonist of IGF1R signaling if the individual exhibits abnormal blood glucose management. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 4.5%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 4.6%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 4.7%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 4.8%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 4.9%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 5.0%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 5.1%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 5.2%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 5.3%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 5.4%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 5.5%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 5.6%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 5.7%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 5.8%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 5.9%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 6.0%. In some embodiments, an individual exhibits abnormal blood glucose management if the measurement of HbA1c is at least about 6.When it is 1%, it indicates abnormal blood glucose management. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 6.2%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 6.3%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 6.4%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 6.5%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 6.6%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 6.7%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 6.8%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 6.9%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 7.0%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 7.1%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 7.2%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 7.3%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 7.4%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 7.5%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 7.6%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 7.7%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 7.8%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 7.9%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 8.When it is 0%, it indicates abnormal blood glucose management. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 8.5%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is at least about 9.0%. In some embodiments, an individual shows abnormal blood glucose management when the measurement of HbA1c is 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%, or 8%, or any percentage greater than 8%. In some embodiments, the blood glucose management test includes an oral glucose tolerance test. In some embodiments, the oral glucose tolerance test includes measuring the individual's response to glucose. In some embodiments, the oral glucose tolerance test includes subjecting the individual to a fasting period over a certain 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, 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 period is about 6 hours to about 18 hours, about 6 hours to about 17.5 hours, about 6 hours to about 17 hours, about 6 hours to about 16.5 hours, about 6 hours to about 16 hours, about 6 hours to about 15.5 hours, about 6 hours to about 15 hours, about 6 hours to about 14.5 hours, about 6 hours to about 14 hours, about 6 hours to about 13.5 hours, about 6 hours to about 13 hours, about 6 hours to about 12.5 hours, about 6 hours to about 12 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 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 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.

[0070] In some embodiments, an oral glucose tolerance test includes measuring a first blood glucose level of an individual after fasting. In some embodiments, an oral glucose tolerance test includes orally administering a certain amount of sugar to the individual after fasting. In some embodiments, an oral glucose tolerance test includes orally administering a certain amount of sugar to the individual after measuring the first blood glucose level of the individual. In some embodiments, an oral glucose tolerance test includes orally administering a certain amount of glucose to the individual after fasting. In some embodiments, an oral glucose tolerance test includes orally administering a certain amount of glucose to the individual after measuring the first blood glucose level of the individual. In some embodiments, the amount of sugar or glucose administered is about 50 to 150 grams (g), for example, about 50 g, 51 g, 52 g, 53 g, 54 g, 55 g, 56 g, 57 g, 58 g, 59 g, 60 g, 61 g, 62 g, 63 g, 64 g, 65 g, 66 g, 67 g, 68 g, 69 g, 70 g, 71 g, 72 g, 73 g, 74 g, 75 g, 76 g, 77 g, 78 g, 79 g, 80 g, 81 g, 82 g, 83 g, 84 g, 85 g, 86 g, 87 g, 88 g, 89 g, 90 g, 91 g, 92 g, 93 g, 94 g, 95 g, 96 g, 97 g, 98 g, 99 g, 100 g, 101 g, 102 g, 103 g, 104 g, 105 g, 106 g, 107 g, 108 g, 109 g, 110 g, 111 g, 112 g, 113 g, 114 g, 115 g, 116 g, 117 g, 118 g, 119 g, 120 g, 121 g, 122 g, 123 g, 124 g, 125 g, 126 g, 127 g, 128 g, 129 g, 130 g, 131 g, 132 g, 133 g, 134 g, 135 g, 136 g, 137 g, 138 g, 139 g, 140 g, 141 g, 142 g, 143 g, 144 g, 145 g, 146 g, 147 g, 148 g, 149 g, or about 150 g, or any amount therebetween. In some embodiments, the amount of sugar administered is about 75 g. In some embodiments, the amount of glucose administered is about 75 g. In some embodiments, an oral glucose tolerance test includes orally administering about 75 g of sugar dissolved in an aqueous medium to the individual after fasting. In some embodiments, an oral glucose tolerance test includes orally administering about 75 g of glucose dissolved in an aqueous medium to the individual after fasting.In some embodiments, an oral glucose tolerance test includes measuring a first blood glucose level of an individual and then orally administering to the individual about 75 g of sugar dissolved in an aqueous medium. In some embodiments, an oral glucose tolerance test includes measuring a first blood glucose level of an individual and then orally administering to the individual about 75 g of glucose dissolved in an aqueous medium. In some embodiments, the aqueous medium includes water.

[0071] In some embodiments, the oral glucose tolerance test includes measuring a second blood glucose level of an individual after oral ingestion of sugar or glucose by the individual. In some embodiments, the duration between oral ingestion of sugar or glucose by the individual and measurement of the second blood glucose level of the individual is from about 30 minutes (min) to about 6 hours, such as about 30 minutes, 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 about 75 g of sugar or glucose dissolved in an aqueous medium by the individual and measurement of the second blood glucose level of the individual is from about 30 minutes (min) to about 6 hours, such as about 30 minutes, 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 sugar or glucose dissolved in an aqueous medium by the individual and measurement of the second blood glucose level of the individual is from about 30 minutes to about 6 hours, from about 30 minutes to about 5.5 hours, from about 30 minutes to about 5 hours, from about 30 minutes to about 4.5 hours, from about 30 minutes to about 4 hours, from about 30 minutes to about 3.5 hours, from about 30 minutes to about 3 hours, from about 30 minutes to about 2.5 hours, from about 30 minutes to about 2 hours, from about 30 minutes to about 1.5 hours, from about 30 minutes to about 1 hour, from about 1 hour to about 6 hours, from about 1 hour to about 5.5 hours, from about 1 hour to about 5 hours, from about 1 hour to about 4.5 hours, from about 1 hour to about 4 hours, from about 1 hour to about 3.5 hours, from about 1 hour to about 3 hours, from about 1 hour to about 2.5 hours, from about 1 hour to about 2 hours, from about 1 hour to about 1.5 hours, from about 2 hours to about 6 hours, from about 2 hours to about 5.5 hours, from about 2 hours to about 5 hours, from about 2 hours to about 4.5 hours, from about 2 hours to about 4 hours, from about 2 hours to about 3.5 hours, from about 2 hours to about 3 hours, from about 2 hours to about 2.5 hours, from about 2.5 hours to about 6 hours, from about 2.5 hours to about 5.5 hours, from about 2.5 hours to about 5 hours, from about 2.5 hours to about 4.5 hours, from about 2.5 hours to about 4 hours, from about 2.5 hours to about 3.5 hours, from about 2.5 hours to about 3 hours, from about 3 hours to about 6 hours, from about 3 hours to about 5.5 hours, from about 3 hours to about 5 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 4 hours to about 6 hours, from about 4 hours to about 5.5 hours, from about 4 hours to about 5 hours, or from about 4 hours to about 4.5 hours.In some embodiments, the duration between oral ingestion of 75 g of sugar or glucose dissolved in an aqueous medium and measurement of a second blood glucose value of the individual is from about 30 minutes to about 6 hours, from about 30 minutes to about 5.5 hours, from about 30 minutes to about 5 hours, from about 30 minutes to about 4.5 hours, from about 30 minutes to about 4 hours, from about 30 minutes to about 3.5 hours, from about 30 minutes to about 3 hours, from about 30 minutes to about 2.5 hours, from about 30 minutes to about 2 hours, from about 30 minutes to about 1.5 hours, from about 30 minutes to about 1 hour, from about 1 hour to about 6 hours, from about 1 hour to about 5.5 hours, from about 1 hour to about 5 hours, from about 1 hour to about 4.5 hours, from about 1 hour to about 4 hours, from about 1 hour to about 3.5 hours, from about 1 hour to about 3 hours, from about 1 hour to about 2.5 hours, from about 1 hour to about 2 hours, from about 1 hour to about 1.5 hours, from about 1.5 hours to about 6 hours, from about 1.5 hours to about 5.5 hours, from about 1.5 hours to about 5 hours, from about 1.5 hours to about 4.5 hours, from about 1.5 hours to about 4 hours, from about 1.5 hours to about 3.5 hours, from about 1.5 hours to about 3 hours, from about 1.5 hours to about 2.5 hours, from about 1.5 hours to about 2 hours, from about 2 hours to about 6 hours, from about 2 hours to about 5.5 hours, from about 2 hours to about 5 hours, from about 2 hours to about 4.5 hours, from about 2 hours to about 4 hours, from about 2 hours to about 3.5 hours, from about 2 hours to about 3 hours, from about 2 hours to about 2.5 hours, from about 2.5 hours to about 6 hours, from about 2.5 hours to about 5.5 hours, from about 2.5 hours to about 5 hours, from about 2.5 hours to about 4.5 hours, from about 2.5 hours to about 4 hours, from about 2.5 hours to about 3.5 hours, from about 2.5 hours to about 3 hours, from about 3 hours to about 6 hours, from about 3 hours to about 5.5 hours, from about 3 hours to about 5 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.

[0072] In some embodiments, the duration between the oral ingestion of 75 g of sugar or glucose dissolved in an aqueous medium by an individual and the measurement of the individual's second blood glucose level is about 1 hour. In some embodiments, the duration between the oral ingestion of about 75 g of sugar or glucose dissolved in an aqueous medium by an individual and the measurement of the individual's second blood glucose level is about 1.5 hours. In some embodiments, the duration between the oral ingestion of about 75 g of sugar or glucose dissolved in an aqueous medium by an individual and the measurement of the individual's second blood glucose level is about 2 hours. In some embodiments, the duration between the oral ingestion of about 75 g of sugar or glucose dissolved in an aqueous medium by an individual and the measurement of the individual's second blood glucose level is about 2.5 hours. In some embodiments, the duration between the oral ingestion of about 75 g of sugar or glucose dissolved in an aqueous medium by an individual and the measurement of the individual's second blood glucose level is about 3 hours. In some embodiments, the duration between the oral ingestion of about 75 g of sugar or glucose dissolved in an aqueous medium by an individual and the measurement of the individual's second blood glucose level is about 3.5 hours. In some embodiments, the duration between the oral ingestion of about 75 g of sugar or glucose dissolved in an aqueous medium by an individual and the measurement of the individual's second blood glucose level is about 4 hours.

[0073] In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 250 milligrams per deciliter (mg / dL) or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 245 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 240 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 235 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 230 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 225 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 220 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 215 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 210 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 205 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 200 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 195 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 190 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's second blood glucose value measured by an oral glucose tolerance test is 185 mg / dL or less.In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 180 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 175 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 170 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 165 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 160 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 155 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 150 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 145 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 140 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 135 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 130 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 125 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 120 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 115 mg / dL or less.In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 110 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 105 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the second blood glucose value of the individual measured by an oral glucose tolerance test is 100 mg / dL or less.

[0074] In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 250 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 245 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 240 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 235 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 230 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 225 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 220 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 215 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium.In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 210 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 205 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 200 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 195 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 190 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 185 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 180 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 175 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium.In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 170 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 165 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 160 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 155 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 150 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 145 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 140 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 135 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium.In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 130 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 125 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 120 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 115 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 110 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 105 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows normal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is 100 mg / dL or less, and the second blood glucose value is measured approximately 2 hours after oral ingestion of about 75 g of glucose or sugar dissolved in an aqueous medium.

[0075] In some embodiments, the second blood glucose value of the individual, as measured by an oral glucose tolerance test, is from about 0 to about 250 mg / dL, 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, 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, 150 mg / dL, 151 mg / dL, 152 mg / dL, 153 mg / dL, 154 mg / dL, 155 mg / dL, 156 mg / dL, 157 mg / dL, 158 mg / dL, 159 mg / dL, 160 mg / dL, 161 mg / dL, 162 mg / dL, 163 mg / dL, 164 mg / dL, 165 mg / dL, 166 mg / dL, 167 mg / dL, 168 mg / dL, 169 mg / dL, 170 mg / dL, 171 mg / dL, 172 mg / dL, 173 mg / dL, 174 mg / dL, 175 mg / dL, 176 mg / dL, 177 mg / dL, 178 mg / dL, 179 mg / dL, 180 mg / dL, 181 mg / dL, 182 mg / dL, 183 mg / dL, 184 mg / dL, 185 mg / dL, 186 mg / dL, 187 mg / dL, 188 mg / dL, 189 mg / dL, 190 mg / dL, 191 mg / dL, 192 mg / dL, 193 mg / dL, 194 mg / dL, 195 mg / dL, 196 mg / dL, 197 mg / dL, 198 mg / dL, 199 mg / dL, 200 mg / dL, 201 mg / dL, 202 mg / dL, 203 mg / dL, 204 mg / dL, 205 mg / dL, 206 mg / dL, 207 mg / dL, 208 mg / dL, 209 mg / dL, 210 mg / dL, 211 mg / dL, 212 mg / dL, 213 mg / dL, 214 mg / 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 / dLWhen it is 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 in between, it indicates normal blood glucose management.

[0076] In some embodiments, during an oral glucose tolerance test, when the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium, the individual has a second blood glucose value of 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, 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, 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, 150 mg / dL, 151 mg / dL, 152 mg / dL, 153 mg / dL, 154 mg / dL, 155 mg / dL, 156 mg / dL, 157 mg / dL, 158 mg / dL, 159 mg / dL, 160 mg / dL, 161 mg / dL, 162 mg / dL, 163 mg / dL, 164 mg / dL, 165 mg / dL, 166 mg / dL, 167 mg / dL, 168 mg / dL, 169 mg / dL, 170 mg / dL, 171 mg / dL, 172 mg / dL, 173 mg / dL, 174 mg / dL, 175 mg / dL, 176 mg / dL, 177 mg / dL, 178 mg / dL, 179 mg / dL, 180 mg / dL, 181 mg / dL, 182 mg / dL, 183 mg / dL, 184 mg / dL, 185 mg / dL, 186 mg / dL, 187 mg / dL, 188 mg / dL, 189 mg / dL, 190 mg / dL, 191 mg / dL, 192 mg / dL, 193 mg / dL, 194 mg / dL, 195 mg / dL, 196 mg / dL, 197 mg / dL, 198 mg / dL, 199 mg / dL, 200 mg / dL, 201 mg / dL, 202 mg / dL, 203 mg / dL, 204 mg / dL, 205 mg / dL, 206 mg / dL, 207 mg / dL, 208 mg / dL, 209 mg / dL, 210 mg / dL, 211 mg / dL, 212 mg / dL, 213 mg / dL, 214 mg / 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,When it is 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, 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 in between, it indicates normal blood glucose management.

[0077] In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 250 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 240 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 230 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 220 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 210 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 200 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 190 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 180 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 170 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 160 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 150 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 140 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 130 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 120 mg / dL.In some embodiments, an individual exhibits abnormal blood glucose management if a second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 110 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if a second blood glucose value of the individual measured by an oral glucose tolerance test is greater than 100 mg / dL.

[0078] In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 250 mg / dL, where the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 240 mg / dL, where the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 230 mg / dL, where the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 220 mg / dL, where the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 210 mg / dL, where the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 200 mg / dL, where the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 190 mg / dL, where the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 180 mg / dL, where the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium.In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 170 mg / dL and the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 160 mg / dL and the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 150 mg / dL and the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 140 mg / dL and the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 130 mg / dL and the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 120 mg / dL and the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 110 mg / dL and the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium. In some embodiments, an individual shows abnormal blood glucose management when the second blood glucose value of the individual, measured by an oral glucose tolerance test, is greater than 100 mg / dL and the second blood glucose value is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium.

[0079] In some embodiments, the second blood glucose value of the individual, as measured by an oral glucose tolerance test, is greater than about 100 mg / dL, for example, 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 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, 150 mg / dL, 151 mg / dL, 152 mg / dL, 153 mg / dL, 154 mg / dL, 155 mg / dL, 156 mg / dL, 157 mg / dL, 158 mg / dL, 159 mg / dL, 160 mg / dL, 161 mg / dL, 162 mg / dL, 163 mg / dL, 164 mg / dL, 165 mg / dL, 166 mg / dL, 167 mg / dL, 168 mg / dL, 169 mg / dL, 170 mg / dL, 171 mg / dL, 172 mg / dL, 173 mg / dL, 174 mg / dL, 175 mg / dL, 176 mg / dL, 177 mg / dL, 178 mg / dL, 179 mg / dL, 180 mg / dL, 181 mg / dL, 182 mg / dL, 183 mg / dL, 184 mg / dL, 185 mg / dL, 186 mg / dL, 187 mg / dL, 188 mg / dL, 189 mg / dL, 190 mg / dL, 191 mg / dL, 192 mg / dL, 193 mg / dL, 194 mg / dL, 195 mg / dL, 196 mg / dL, 197 mg / dL, 198 mg / dL, 199 mg / dL, 200 mg / dL, 201 mg / dL, 202 mg / dL, 203 mg / dL, 204 mg / dL,When the concentration is 205 mg / dL, 206 mg / dL, 207 mg / dL, 208 mg / dL, 209 mg / dL, 210 mg / dL, 211 mg / dL, 212 mg / dL, 213 mg / dL, 214 mg / 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, 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, 250 mg / dL, 251 mg / dL, 252 mg / dL, 253 mg / dL, 254 mg / dL, 255 mg / dL, 256 mg / dL, 257 mg / dL, 258 mg / dL, 259 mg / dL, 260 mg / dL, 261 mg / dL, 262 mg / dL, 263 mg / dL, 264 mg / dL, 265 mg / dL, 266 mg / dL, 267 mg / dL, 268 mg / dL, 269 mg / dL, 270 mg / dL, 271 mg / dL, 272 mg / dL, 273 mg / dL, 274 mg / dL, or about 275 mg / dL, or any concentration exceeding about 275 mg / dL, it indicates abnormal blood glucose management.

[0080] In some embodiments, during an oral glucose tolerance test, when the second blood glucose level is measured 2 hours after oral ingestion of 75 g of glucose or sugar dissolved in an aqueous medium, the individual has a second blood glucose level that is greater than about 100 mg / dL, for example, 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 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, 150 mg / dL, 151 mg / dL, 152 mg / dL, 153 mg / dL, 154 mg / dL, 155 mg / dL, 156 mg / dL, 157 mg / dL, 158 mg / dL, 159 mg / dL, 160 mg / dL, 161 mg / dL, 162 mg / dL, 163 mg / dL, 164 mg / dL, 165 mg / dL, 166 mg / dL, 167 mg / dL, 168 mg / dL, 169 mg / dL, 170 mg / dL, 171 mg / dL, 172 mg / dL, 173 mg / dL, 174 mg / dL, 175 mg / dL, 176 mg / dL, 177 mg / dL, 178 mg / dL, 179 mg / dL, 180 mg / dL, 181 mg / dL, 182 mg / dL, 183 mg / dL, 184 mg / dL, 185 mg / dL, 186 mg / dL, 187 mg / dL, 188 mg / dL, 189 mg / dL, 190 mg / dL, 191 mg / dL, 192 mg / dL, 193 mg / dL, 194 mg / dL, 195 mg / dL, 196 mg / dL, 197 mg / dL, 198 mg / dL, 199 mg / dL, 200 mg / dL,If the concentration is 201 mg / dL, 202 mg / dL, 203 mg / dL, 204 mg / dL, 205 mg / dL, 206 mg / dL, 207 mg / dL, 208 mg / dL, 209 mg / dL, 210 mg / dL, 211 mg / dL, 212 mg / dL, 213 mg / dL, 214 mg / 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, 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, 250 mg / dL, 251 mg / dL, 252 mg / dL, 253 mg / dL, 254 mg / dL, 255 mg / dL, 256 mg / dL, 257 mg / dL, 258 mg / dL, 259 mg / dL, 260 mg / dL, 261 mg / dL, 262 mg / dL, 263 mg / dL, 264 mg / dL, 265 mg / dL, 266 mg / dL, 267 mg / dL, 268 mg / dL, 269 mg / dL, 270 mg / dL, 271 mg / dL, 272 mg / dL, 273 mg / dL, 274 mg / dL, or about 275 mg / dL, or any concentration exceeding about 275 mg / dL, it indicates abnormal blood glucose management.

[0081] In some embodiments, the blood glucose management test includes measuring fasting blood glucose. In some embodiments, measuring fasting blood glucose includes subjecting the individual to a fast. In some embodiments, the fast lasts overnight. In some embodiments, the fast lasts from 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 fast 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 11 hours, from about 6 hours to about 10.5 hours, from about 6 hours to about 10 hours, from about 6 hours to about 9.5 hours, from about 6 hours to about 9 hours, from about 6 hours to about 8.5 hours, from about 6 hours to about 8 hours, from about 6 hours to about 7.5 hours, from about 6 hours to about 7 hours, from about 6 hours to about 6.5 hours, from about 7 hours to about 18 hours, from about 7 hours to about 17.5 hours, from about 7 hours to about 17 hours, from about 7 hours to about 16.5 hours, from about 7 hours to about 16 hours, from about 7 hours to about 15.5 hours, from about 7 hours to about 15 hours, from about 7 hours to about 14.5 hours, from about 7 hours to about 14 hours, from about 7 hours to about 13.5 hours, from about 7 hours to about 13 hours, from about 7 hours to about 12.5 hours, from about 7 hours to about 12 hours, from about 7 hours to about 11.5 hours, from about 7 hours to about 11 hours, from about 7 hours to about 10.5 hours, from about 7 hours to about 10 hours, from about 7 hours to about 9.5 hours, from about 7 hours to about 9 hours, from about 7 hours to about 8.5 hours, from about 7 hours to about 8 hours, from about 7 hours to about 7.5 hours, from about 8 hours to about 18 hours, from about 8 hours to about 17.5 hours, from about 8 hours to about 17 hours, from about 8 hours to about 16.5 hours, from about 8 hours to about 16 hours, from about 8 hours to about 15.5 hours, from about 8 hours to about 15 hours, from about 8 hours to about 14.5 hours, from about 8 hours to about 14 hours, from about 8 hours to about 13.5 hours, from about 8 hours to about 13 hours, from 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.It continues for 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.

[0082] In some embodiments, measuring a fasting blood glucose test comprises measuring the blood glucose level of an individual after fasting. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 150 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 149 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 148 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 147 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 146 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 145 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 144 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 143 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 142 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 141 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 140 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 139 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 138 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 137 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 136 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 135 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the blood glucose level of the individual after fasting is about 134 mg / dL or less.In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 133 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 132 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 131 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 130 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 129 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 128 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 127 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 126 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 125 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 124 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 123 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 122 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 121 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 120 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 119 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 118 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 117 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's post - fasting blood glucose level is about 116 mg / dL or less.In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 115 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 114 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 113 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 112 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 111 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 110 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 109 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 108 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 107 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 106 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 105 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 104 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 103 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 102 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 101 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 100 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 99 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 98 mg / dL or less.In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 97 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 96 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 95 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 94 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 93 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 92 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 91 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 90 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 89 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 88 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 87 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 86 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 85 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 84 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 83 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 82 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 81 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after fasting is about 80 mg / dL or less.In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 79 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 78 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 77 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 76 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's post - fasting blood glucose level is about 75 mg / dL or less.

[0083] In some embodiments, the blood glucose level of the individual after fasting is from about 0 to about 150 mg / dL, 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,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 in between, indicates normal blood glucose management.,

[0084] In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 150 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 149 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 148 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 147 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 146 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 145 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 144 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 143 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 142 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 141 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 140 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 139 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 138 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 137 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 136 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 135 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 134 mg / dL or less.In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 133 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 132 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 131 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 130 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 129 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 128 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 127 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 126 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 125 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 124 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 123 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 122 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 121 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 120 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 119 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 118 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 117 mg / dL or less.In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 116 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 115 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 114 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 113 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 112 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 111 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 110 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 109 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 108 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 107 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 106 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 105 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 104 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 103 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 102 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 101 mg / dL or less. In some embodiments, an individual demonstrates normal blood glucose management when the individual's blood glucose level after an overnight fast is 100 mg / dL or less.In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 99 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 98 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 97 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 96 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 95 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 94 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 93 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 92 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 91 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 90 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 89 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 88 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 87 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 86 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 85 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 84 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management when the individual's blood glucose level after an overnight fast is about 83 mg / dL or less.In some embodiments, an individual exhibits normal blood glucose management if the individual's blood glucose level after an overnight fast is about 82 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the individual's blood glucose level after an overnight fast is about 81 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the individual's blood glucose level after an overnight fast is about 80 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the individual's blood glucose level after an overnight fast is about 79 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the individual's blood glucose level after an overnight fast is about 78 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the individual's blood glucose level after an overnight fast is about 77 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the individual's blood glucose level after an overnight fast is about 76 mg / dL or less. In some embodiments, an individual exhibits normal blood glucose management if the individual's blood glucose level after an overnight fast is about 75 mg / dL or less.

[0085] In some embodiments, the individual has a blood glucose level of the individual after an overnight fast that is from about 0 to about 150 mg / dL, 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,When it is 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 in between, it indicates normal blood glucose management.

[0086] In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 150 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 149 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 148 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 147 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 146 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 145 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 144 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 143 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 142 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 141 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 140 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 139 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 138 mg / dL or less.In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 137 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 136 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 135 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 134 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 133 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 132 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 131 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 130 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 129 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 128 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 127 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 126 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 125 mg / dL or less.In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 124 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 123 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 122 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 121 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 120 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 119 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 118 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 117 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 116 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 115 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 114 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 113 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual shows normal blood glucose management if the individual's blood glucose level after fasting is about 112 mg / dL or less.In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 111 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 110 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 109 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 108 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 107 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 106 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 105 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 104 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 103 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 102 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 101 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 100 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 99 mg / dL or less.In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 98 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 97 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 96 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 95 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 94 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 93 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 92 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 91 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 90 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 89 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 88 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 87 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 86 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 85 mg / dL or less.In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 84 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 83 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 82 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 81 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 80 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours. The individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 79 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 78 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 77 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 76 mg / dL or less. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits normal blood glucose management if the individual's blood glucose level after fasting is about 75 mg / dL or less.

[0087] In some embodiments, normal blood glucose management is established on the day of administration of the IGF1R inhibitor. In some embodiments, normal blood glucose management is established 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 21, 28, 35, 42, 48, or 56 days before administration of the IGF1R inhibitor.

[0088] In some embodiments, when fasting lasts from about 8 hours to about 16 hours, the blood glucose level of the individual after fasting is from 0 to about 150 mg / dL, 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,When it is 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 in between, it indicates normal blood glucose management.

[0089] In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 150 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 149 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 148 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 147 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 146 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 145 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 144 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 143 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 142 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 141 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 140 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 139 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 138 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 137 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 136 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 135 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 134 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 133 mg / dL.In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 132 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 131 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 130 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 129 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 128 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 127 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 126 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 125 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 124 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 123 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 122 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 121 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 120 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 119 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 118 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 117 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 116 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 115 mg / dL.In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 114 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 113 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 112 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 111 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 110 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 109 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 108 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 107 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 106 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 105 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 104 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 103 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 102 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 101 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 100 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 99 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 98 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 97 mg / dL.In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 96 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 95 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 94 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 93 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 92 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 91 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 90 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 89 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 88 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 87 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 86 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 85 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 84 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 83 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 82 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 81 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 80 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 79 mg / dL.In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 78 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 77 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 76 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 75 mg / dL.

[0090] In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 75 mg / dL, for example, 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, 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, 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 150 mg / dL, or any concentration greater than 150 mg / dL.

[0091] In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 150 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 149 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 148 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 147 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 146 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 145 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 144 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 143 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 142 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 141 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 140 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 139 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 138 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 137 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 136 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 135 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 134 mg / dL.In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 133 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 132 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 131 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 130 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 129 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 128 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 127 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 126 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 125 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 124 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 123 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 122 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 121 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 120 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 119 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 118 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 117 mg / dL.In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 116 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 115 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 114 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 113 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 112 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 111 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 110 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 109 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 108 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 107 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 106 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 105 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 104 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 103 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 102 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 101 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 100 mg / dL.In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 99 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 98 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 97 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 96 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 95 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 94 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 93 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 92 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 91 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 90 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 89 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 88 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 87 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 86 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 85 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 84 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 83 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 82 mg / dL.In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 81 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 80 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 79 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 78 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 77 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 76 mg / dL. In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than about 75 mg / dL.

[0092] In some embodiments, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after an overnight fast is greater than 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, 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, 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 greater than 150 mg / dL.

[0093] In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 150 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 149 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 148 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 147 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 146 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 145 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 144 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 143 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 142 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 141 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 140 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 139 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 138 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 137 mg / dL.In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 136 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 135 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 134 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 133 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 132 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 131 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 130 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 129 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 128 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 127 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 126 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 125 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 124 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 123 mg / dL.In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 122 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 121 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 120 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 119 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 118 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 117 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 116 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 115 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 114 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 113 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 112 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 111 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 110 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 109 mg / dL.In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 108 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 107 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 106 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 105 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 104 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 103 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 102 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 101 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 100 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 99 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 98 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 97 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 96 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 95 mg / dL.In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 94 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 93 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 92 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 91 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 90 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 89 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 88 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 87 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 86 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 85 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 84 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 83 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 82 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 81 mg / dL.In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 80 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 79 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 78 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 77 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 76 mg / dL. In some embodiments, when fasting lasts for about 8 to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 75 mg / dL.

[0094] In some embodiments, when fasting lasts from about 8 hours to about 16 hours, an individual exhibits abnormal blood glucose management if the individual's blood glucose level after fasting is greater than about 75 mg / dL, such as, for example, 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, 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, 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 greater than 150 mg / dL.

[0095] In some embodiments, the blood glucose management test includes measurement of non-fasting blood glucose. In some embodiments, measurement of non-fasting blood glucose includes measuring an individual's blood glucose level or blood sugar level without subjecting the individual to a fast. In some embodiments, measurement of non-fasting blood glucose includes measuring an individual's blood glucose level or blood sugar level at any time without subjecting the individual to a fast.

[0096] In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 250 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 249 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 248 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 247 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 246 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 245 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 244 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 243 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 242 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 241 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 240 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 239 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 238 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 237 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 236 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 235 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 234 mg / dL, the individual shows normal blood glucose management.In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 233 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 232 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 231 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 230 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 229 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 228 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 227 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 226 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 225 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 224 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 223 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 222 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 221 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 220 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 219 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 218 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 217 mg / dL, the individual shows normal blood glucose management.In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 216 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 215 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 214 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 213 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 212 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 211 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 210 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 209 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 208 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 207 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 206 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 205 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 204 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 203 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 202 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 201 mg / dL, the individual exhibits normal blood glucose management. In some embodiments, when an individual exhibits a non-fasting blood glucose level of less than about 200 mg / dL, the individual exhibits normal blood glucose management.In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 199 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 198 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 197 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 196 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 195 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 194 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 193 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 192 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 191 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 190 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 189 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 188 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 187 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 186 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 185 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual shows a non-fasting blood glucose level of less than about 184 mg / dL, the individual shows normal blood glucose management. In some embodiments, when an individual s...

Claims

1. A method for obtaining the results of a blood glucose control test as an indicator for monitoring an individual with pre-existing hyperglycemia, prediabetes, or diabetes who is being treated for thyroid eye disease, wherein the method is Obtaining the results of the blood glucose control test from the individual being treated with an IGF1R signaling antagonist. A method comprising the following, wherein the IGF1R signaling antagonist is an antibody that binds to IGF1R, and the measurement of HbA1c of 6.5% or higher based on the results of the blood glucose control test, or the measurement of fasting blood glucose of 126 mg / dL or higher after an overnight fast, indicates that the treatment of the individual with the IGF1R signaling antagonist should be discontinued.

2. Interruption of treatment with the IGF1R signaling antagonist indicates that the individual should be treated with an antidiabetic drug, The method according to claim 1, further comprising obtaining the results of a second blood glucose control test from the individual, wherein the measurement of HbA1c less than 6.5% by the second blood glucose control test, or the measurement of fasting blood glucose less than 126 mg / dL after an overnight fast, indicates that the IGF1R signaling antagonist should be administered to the individual.

3. The method according to claim 2, wherein the antidiabetic drug is selected from insulin, metformin, pioglitazone, rosiglitazone, acarbose, miglitol, bromocriptine, alogliptin, linagliptin, saxagliptin, sitagliptin, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tilzepatide, nateglinide, repaglinide, canagliflozin, dapagliflozin, empagliflozin, erzgliflozin, glimepiride, gliclazide, glipizide, or a combination thereof.

4. A composition for use in a method for treating thyroid eye disease in an individual having existing hyperglycemia, prediabetes, or diabetes, wherein the composition comprises an IGF1R signaling antagonist, and the method is a) If the individual shows an HbA1c measurement of less than 6.5% by a first blood glucose control test, or a fasting blood glucose measurement of less than 126 mg / dL after an overnight fast, select the individual for treatment with the IGF1R signaling antagonist; b) administering the composition having a first dose of the IGF1R signaling antagonist to the individual; and c) Obtaining the results of a second blood glucose control test from the individual being treated with the IGF1R signaling antagonist. A composition comprising, wherein the IGF1R signaling antagonist is an antibody that binds to IGF1R.

5. The composition according to claim 4, wherein the measurement of HbA1c of 6.5% or higher based on the results of the second test for blood glucose control, or the measurement of fasting blood glucose of 126 mg / dL or higher after an overnight fast, indicates that the treatment of the individual with the IGF1R signaling antagonist should be discontinued.

6. The method further comprises administering to the individual a second dose of the composition having the IGF1R signaling antagonist if the individual shows a measurement of HbA1c of 6.5% or more as a result of the second test for blood glucose control, or a measurement of fasting blood glucose of 126 mg / dL or more after an overnight fast, wherein the second dose is lower than the first dose, according to claim 4.

7. The composition according to claim 4, further comprising treating the individual with an antidiabetic drug if the individual shows a measurement of HbA1c of 6.5% or more as a result of the second test for blood glucose control, or a measurement of fasting blood glucose of 126 mg / dL or more after an overnight fast.

8. The composition according to claim 7, wherein the antidiabetic agent is selected from insulin, metformin, pioglitazone, rosiglitazone, acarbose, miglitol, bromocriptine, alogliptin, linagliptin, saxagliptin, sitagliptin, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tilzepatide, nateglinide, repaglinide, canagliflozin, dapagliflozin, empagliflozin, erzgliflozin, glimepiride, gliclazide, glipizide, or a combination thereof.

9. A composition for use in a method for treating thyroid eye disease in an individual having existing hyperglycemia, prediabetes, or diabetes, wherein the composition comprises one or more antidiabetic drugs and is administered in combination with a certain dose of an IGF1R signaling antagonist, and the method is a) Administering the composition in order to lower blood glucose levels; and b) Administering a certain dose of the IGF1R signaling antagonist to the individual. A composition comprising, wherein the IGF1R signaling antagonist is an antibody that binds to IGF1R.

10. The composition according to claim 9, wherein the antidiabetic agent is selected from insulin, metformin, pioglitazone, rosiglitazone, acarbose, miglitol, bromocriptine, alogliptin, linagliptin, saxagliptin, sitagliptin, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tilzepatide, nateglinide, repaglinide, canagliflozin, dapagliflozin, empagliflozin, erzgliflozin, glimepiride, gliclazide, glipizide, or a combination thereof.

11. A composition for use in a method for treating thyroid eye disease in an individual having existing hyperglycemia, prediabetes, or diabetes, characterized in that the composition comprises a certain dose of an IGF1R signaling antagonist and is administered in combination with one or more antidiabetic drugs, wherein the method is a) Administering one or more antidiabetic drugs to lower blood glucose levels; and b) Administering a certain dose of the composition to the individual. A composition comprising, wherein the IGF1R signaling antagonist is an antibody that binds to IGF1R.

12. The composition according to claim 11, wherein the antidiabetic agent is selected from insulin, metformin, pioglitazone, rosiglitazone, acarbose, miglitol, bromocriptine, alogliptin, linagliptin, saxagliptin, sitagliptin, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tilzepatide, nateglinide, repaglinide, canagliflozin, dapagliflozin, empagliflozin, erzgliflozin, glimepiride, gliclazide, glipizide, or a combination thereof.

13. A combination for use in a method for treating thyroid eye disease in an individual having existing hyperglycemia, prediabetes or diabetes, wherein the combination comprises one or more antidiabetic drugs and a certain dose of an IGF1R signaling antagonist, and the method is a) Administering one or more antidiabetic drugs to lower blood glucose levels; and b) Administering a certain dose of the IGF1R signaling antagonist. A combination comprising the above, wherein the IGF1R signaling antagonist is an antibody that binds to IGF1R.

14. The combination according to claim 13, wherein the antidiabetic agent is selected from insulin, metformin, pioglitazone, rosiglitazone, acarbose, miglitol, bromocriptine, alogliptin, linagliptin, saxagliptin, sitagliptin, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tilzepatide, nateglinide, repaglinide, canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, glimepiride, gliclazide, glipizide, or a combination thereof.

15. The antibody that binds to IGF1R, a) Heavy chains including the following: (i) A first heavy chain complementarity determination region (HCDR1) containing the amino acid sequence represented by Sequence ID No. 5; (ii) A second heavy chain complementarity determination region (HCDR2) containing the amino acid sequence represented by Sequence ID No. 6; and (iii) A third heavy chain complementarity-determining region (HCDR3) containing the amino acid sequence represented by Sequence ID No. 7; and b) Light chains including the following: (i) A first light chain complementarity determination region (LCDR1) containing the amino acid sequence represented by Sequence ID No. 8; (ii) A second light chain complementarity determination region (LCDR2) containing the amino acid sequence represented by Sequence ID No. 9; and (iii) A third light chain complementarity determination region (LCDR3) containing the amino acid sequence represented by Sequence ID No.

10. A method according to any one of claims 1 to 3, a composition according to any one of claims 4 to 12, and a combination according to claim 13 or 14.

16. The antibody that binds to IGF1R is a) Heavy chain variable domain containing the amino acid sequence of SEQ ID NO: 3; and b) Light chain variable domain containing the amino acid sequence of SEQ ID NO: 4 A method according to any one of claims 1 to 3, a composition according to any one of claims 4 to 12, and a combination according to claim 13 or 14.

17. The antibody that binds to IGF1R is a) Heavy chain containing the amino acid sequence of SEQ ID NO: 1; and b) Light chain containing the amino acid sequence of SEQ ID NO: 2 A method according to any one of claims 1 to 3, a composition according to any one of claims 4 to 12, and a combination according to claim 13 or 14.

18. The method according to any one of claims 1 to 3, the composition according to any one of claims 4 to 12, and the combination according to claim 13 or 14, wherein the antibody that binds to IGF1R is teprotumumab.

19. The method according to any one of claims 1 to 3, wherein the antibody that binds to IGF1R is ganitumab, figtumumab, xixtumumab, darotuzumab, lobatumumab, or istilatumab, the composition according to any one of claims 4 to 12, and the combination according to claim 13 or 14.

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