Abstract:
Once thought to be an adult disease, type 2 diabetes has emerged as an increasingly prevalent health condition in pediatric populations in parallel with the widespread pediatric obesity epidemic. The oral glucose tolerance test (OGTT) is traditionally used to either diagnose diabetes or capture prediabetes, including impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), a state of heightened risk for future type 2 diabetes. However, limitations of IFG and IGT were described by prospective epidemiological studies in adults demonstrating that only one-half of prediabetic individuals eventually convert to type 2 diabetes. For this reason, there is increasing interest in finding novel biomarkers derived from the OGTT that can identify metabolic abnormalities beyond fasting and 2-h glucose concentrations. Such emerging risk indicators include OGTT-glucose-response-curve and 1-h glucose concentration. For this presentation, the followings are discussed: 1) a core defect in the pathogenesis of type 2 diabetes which is pancreatic β-cell failure in the face of severe insulin resistance in obese youth; 2) recent findings of adipose tissue insulin resistance in obese youth across the spectrum of glucose tolerance from normal glucose tolerance to IGT to type 2 diabetes; 3) differences in disease process between obese youth vs. obese adults; 4) introduction of emerging biomarkers that are effective to identify obese youth who are at highest risk for type 2 diabetes by providing evidence of verifications against the gold standard measures of type 2 diabetes pathophysiological factors (hyperinsulinemic-euglycemic clamp-, hyperglycemic clamp-, and IVGTT-measured insulin sensitivity and β-cell function); and 5) effects of lifestyle intervention on emerging biomarkers of type 2 diabetes risk in obese youth.
