Novel Biomarker for Development of T2D

The investigators wants to determine if 11β-HSD1 activity will be positively associated, and 5α-reductase activity negatively associated, with (a) degree of insulin resistance defined by the homeostatic model assessment of insulin resistance index (HOMA-IR) and (b) worsening glycemic control defined by higher HbA1c and impaired fasting glucose in a group of obese children and young adults with or without type 2 diabetes compared to lean children and young adults without diabetes. The investigators also want to identify key metabolic signatures associated with diabetes using metabolomic profiling.

The overarching hypothesis is that increases in whole body 11β-HSD1 activity precede and presage the development of type 2 diabetes (T2D) in high-risk obese adolescents, serving as a critical determinant of insulin resistance and glucose intolerance. The increase in 11β-HSD1 activity, in combination with decreases in 5α-reductase activity, will increase tissue cortisol production, promoting the development of insulin resistance and the metabolic syndrome and predisposing to T2D. The investigators predict that increases in 11β-HSD1 activity will be detected in obese children prior to the development of insulin resistance and glucose intolerance and that the progressive increases in 11β-HSD1 will correlate with progressive decreases in insulin sensitivity and glucose tolerance. Given preliminary findings, the investigators also predict that increases in 11β-HSD1 will be greater and occur earlier in development in males than females. This could establish 11β-HSD1 activity as a novel, non-invasive biomarker for progression to, or for development of, glucose intolerance and T2D. The identification of 11β-HSD1 as a biomarker that predicts T2D would have critical clinical import, allowing us to identify obese children and adults at highest risk of metabolic decompensation. Studies of 11β-HSD1 in obese subjects with varying degrees of IR and glucose intolerance will also narrow critical gaps in the understanding of the pathogenesis of T2D. The investigators would like to also validate if urine metabolomic profiling can be used for identifying key metabolomic signatures associated with insulin resistance. To that end the investigators would like to examine detailed metabolomic profiles in 24 hour and spot urine samples. The study population will include 50 obese adolescents with T2D, 50 obese adolescents without T2D and 50 age, gender, race and pubertal status-matched normal weight controls. The subjects will be recruited at the Healthy Lifestyle Program at Duke, Diabetes Clinics at Lenox Baker Children's Hospital and Roxboro Clinics. Study activities include physical exam and medical history, vitals, laboratory tests (only for obese adolescents), urine testing for sugar (only for normal weight adolescents), 24 hour urine collection, spot urine collection, body fat content measurement, and food and activity questionnaire.