The primary objective of this project was to determine whether a 30kDa adipocyte-secreted protein, adiponectin, has utility as a predictive serum biomarker of glycemic control in normal non-diabetic subjects and patients with type 2 diabetes, following treatment with PPARγ agonists, a class of drugs that is known to decrease insulin resistance and slow progression of disease. A better understanding of the relationship between adiponectin levels and glucose lowering in patients with type 2 diabetes as well as non-diabetics could enhance our knowledge of diabetes pathophysiology and aid in the development of new therapies. Results confirmed previous relationships between adiponectin levels and metabolic parameters, and indicate the robust and predictive utility of adiponectin across the spectrum of glucose tolerance. Specifically, adiponectin increases with decreases in glucose, HbA1C, hematocrit and triglycerides (showing an inverse correlation), and increases with age, body weight, BMI, HDL-cholesterol, BUN and creatinine (showing a positive correlation). Early change (6-8 weeks) in adiponectin is a strong predictor of responders (change from baseline in HbA1C ≥ 0.7 %) at later time points. These findings support adiponectin as a useful predictive biomarker in metabolic diseases related to glucose imbalance.
- Eli Lilly and Co.
- Merck Sharp & Dohme Corp.
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- U.S. Food and Drug Administration
- Joseph P. Menetski, Ph.D., Associate Vice President of Research Partnerships, [email protected]
Retrospective analysis of a combined data set evaluated adiponectin as a predictive biomarker of glycemic control under the following conditions:
- Untreated patients (from the baseline measurements);
- In response to therapy (between groups and within groups change over time);
- At “early” times of treatment (<6 weeks) in order to predict changes in adiponectin itself, HbA1C or fasting glucose at 12 or 52 weeks; and in relation to two specific adverse events (edema and congestive heart failure).
Results & Accomplishments
- Results confirmed previous relationships between adiponectin levels and metabolic parameters, and support the robust and predictive utility of adiponectin across the spectrum of glucose tolerance.
- Utility of adiponectin as a biomarker predictive of glycemic efficacy is demonstrated by collaborative pooling of data from clinical trials conducted by multiple sponsors. Wagner JA, Wright EC, Ennis MM, Prince M, Kochan J, Nunez DJ, Schneider B, Wang MD, Chen Y, Ghosh S, Musser BJ, Vassileva MT.; Clin Pharmacol Ther. 2009 Dec;86(6):619-25