Method of detection of occult pancreatic beta cell dysfunction in normoglycemic patients

Abstract

This invention relates to a method for detecting the presence of or likelihood of a patient of developing occult pancreatic beta cell dysfunction, and a method for detecting the presence of or likelihood of a patient of developing clinically significant post-prandial hyperglycemia. The methods involve (a) measuring a level of alpha-hydroxybutyrate (AHB) in a single fasting baseline biological sample of the patient; (b) comparing the level of AHB in the single fasting baseline biological sample to a reference AHB level; and (c) determining the presence of or likelihood of developing the disorder in the patient based on the comparison in step (b). An increased AHB level at fasting baseline indicates that a normoglycemic, normo-insulinemic and / or non-dyslipidemic patient has developed or has an increased likelihood of developing occult pancreatic beta cell dysfunction. An increased AHB level at fasting baseline and an elevated glucose level of at least about 155 mg / dL at 30 minutes and / or 1 hour indicates that a normoglycemic, normo-insulinemic and / or non-dyslipidemic patient has developed or has an increased likelihood of developing clinically significant post-prandial hyperglycemia.

Description

PRIORITY CLAIM[0001]This application is a continuation of U.S. patent application Ser. No. 14 / 153,944, filed on Jan. 13, 2014, which claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 61 / 751,328, filed Jan. 11, 2013, U.S. Provisional Application No. 61 / 831,337, filed Jun. 5, 2013, and U.S. Provisional Application No. 61 / 831,405, filed Jun. 5, 2013, all of which are hereby incorporated by reference in their entirety.BACKGROUND[0002]Currently a number of tests exist that can diagnose patients as diabetic or pre-diabetic, including pre-diabetic conditions, such as occult pancreatic beta cell dysfunction or post-prandial hyperglycemia. Such tests include glucose, insulin, pro-insulin, c-peptide, HbAlc, fructosamine, glycation gap, 1,5-anhydroglucitol (1,5-AG), OGTT, CLIX scoring, HOMA IR scoring, and IRI scores based on combinations of AHB, L-GPC, and Oleic Acid weighted by insulin or BMI. Used alone or in combination some of these tests can detect the presence...

AI Technical Summary

Benefits of technology

[0012]A health risk value may be assigned for the patient based on the determination in step (c), The health risk value may be low risk, moderate risk and high risk of occult pancreatic beta cell dysfunction.

[0015]A therapy guidance may be effectuated based on the determination in step (c). Suitable therapy guidance includes one or more of the following: performing a confirmatory OGTT and / or additional diagnostic testing, prescribing a drug therapy, increasing monitoring frequency of patient condition, and recommending appropriate risk-reduction therapy such as making or maintaining diet and lifestyle choices based on the determination in step (c). The therapy guidance may involves administration of antioxidants, administration of anti-coagulants, administration of anti-dyslipidemic drugs, avoidance of drugs or agents known to damage pancreatic cells; discontinued administration of current drug therapy, administration of agents specific for post-prandial hyperglycemia (e.g. cycloset), administration of drugs that enhance, and / or augment, and / or spare pancreatic beta cell function, administration of an anti-viral agent, an immunosuppressant or insulin or an insulin analog or combinations thereof. The therapy guidance may also include one or more of the following: increased frequency of physician's follow-up, referral for oral glucose tolerance test (OGTT) and / or CLIX test, repetition of tests for monitoring disease progression, patient referral for comprehensive testing for type I diabetes; testing for auto-antibodies to pancreatic cell antigens, other biomarkers for autoimmune diseases, viral DNA / RNA and / or antibodies to viral capsid proteins for Enterovirus family members or combinations thereof. A lifestyle choices involve changes in diet and nutrition, changes in exercise, smoking elimination or a combination thereof.

[0028]A health risk value may be assigned for the patient based on the determination in step (c). The health risk value may be low risk, moderate risk and high risk of occult pancreatic beta cell dysfunction.

[0031]A therapy guidance may be effectuated based on the determination in step (c). Suitable therapy guidance includes one or more of the following: performing a confirmatory OGTT and / or additional diagnostic testing, prescribing a drug therapy, increasing monitoring frequency of patient condition, and recommending appropriate risk-reduction therapy such as making or maintaining diet and lifestyle choices based on the determination in step (c). The therapy guidance may involves administration of antioxidants, administration of anti-coagulants, administration of anti-dyslipidemic drugs, avoidance of drugs or agents known to damage pancreatic cells; discontinued administration of current drug therapy, administration of agents specific for post-prandial hyperglycemia (e.g. cycloset), administration of drugs that enhance, and / or augment, and / or spare pancreatic beta cell function, administration of an anti-viral agent, an immunosuppressant or insulin or an insulin analog or combinations thereof. The therapy guidance may also include one or more of the following: increased frequency of physician's follow-up, referral for oral glucose tolerance test (OGTT) and / or CLIX test, repetition of tests for monitoring disease progression, patient referral for comprehensive testing for type I diabetes; testing for auto-antibodies to pancreatic cell antigens, other biomarkers for autoimmune diseases, viral DNA / RNA and / or antibodies to viral capsid proteins for Enterovirus family members or combinations thereof. A lifestyle choices involve changes in diet and nutrition, changes in exercise, smoking elimination or a combination thereof.

Problems solved by technology

Most OGTTs and CLIX scoring require a patient to remain in the doctor's office for 2 hours post dose, and most clinicians only test baseline samples and the 2 hour time point, and not the labor-intensive 3-5 additional times blood draws during the 2-hour period necessary for CLIX scoring, due to labor and cost constraints.

Additionally, complicated and laborious mathematical calculations need to be performed in order to optimize detection of at-risk individuals with these techniques, and kidney function (approximated by blood creatinine levels / eGFR) needs to be accounted for, causing an additional step.

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