β-cell function, insulin sensitivity, and glucose tolerance in obese diabetic and nondiabetic adolescents and young adults

Context: Type 2 diabetes mellitus ( T2DM) is estimated to account for 10 - 45% of incident pediatric diabetes cases. Objective: Our objective was to characterize the metabolic defects underlying T2DM in adolescents and young adults. Design, Setting, and Patients: We conducted a cross-sectional study of islet function and insulin sensitivity in 16 adolescents with T2DM and 13 obese ( OB) and 13 lean (LN) age-matched nondiabetic subjects at a University Medical Center. Intervention: We provided oral and iv glucose tolerance tests. Main Outcome Measures: We measured insulin and glucagon levels, insulin sensitivity, acute insulin responses to iv glucose, and the ratio of proinsulin to immunoreactive insulin. Results: The diabetic subjects had elevated fasting insulin levels and significantly reduced insulin sensitivity ( P < 0.05). The acute insulin response to iv glucose was comparable in the T2DM and LN groups ( P < 0.05 for the OB vs. LN and T2DM), but insulin secretion adjusted for insulin resistance, the disposition index, was severely impaired in the diabetic subjects ( P < 0.05 for the T2DM vs. LN and OB). The ratio of proinsulin to immunoreactive insulin did not differ among the three groups in the basal or stimulated state. Plasma glucagon levels were comparable before and after ingestion of glucose. Conclusions: These findings demonstrate that diabetic adolescents have significant insulin resistance, even compared with subjects of similar obesity and body fatness, and impaired insulin secretion relative to their degree of insulin resistance. However, the adolescent diabetic subjects retained a first-phase insulin response to glucose that was comparable to lean controls and did not have hyperproinsulinemia or hyperglucagonemia.