Objective: Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are considered prediabetic states. There are limited data in pediatrics in regards to their pathophysiology. We investigated differences in insulin sensitivity (IS) and secretion among youth with IFG, IGT, and coexistent IFG/IGT compared to normal glucose tolerance (NGT) and type 2 diabetes (T2DM).

Research Design and Methods: 24 NGT, 13 IFG, 29 IGT, 11 IFG/IGT and 30 T2DM obese adolescents underwent evaluation of hepatic glucose production [6,6-²H₂ glucose], insulin stimulated glucose disposal (Rd-euglycemic clamp), 1^st and 2^nd phase insulin (1^stPI, 2^ndPI) secretion (hyperglycemic clamp); body composition (DEXA), abdominal adiposity (CT) and substrate oxidation (indirect calorimetry).

Results: NGT, prediabetes and T2DM adolescents had similar body composition and abdominal fat distribution. Rd was lower (p=0.009) in T2DM vs NGT. Compared with NGT, 1st PI was lower in IFG, IGT and IFG/IGT with further deterioration in T2DM, p<0.001. Compared with NGT, β-cell function relative to insulin sensitivity (glucose disposition index or GDI) was lower in IFG, IGT, and IFG/IGT (40%, 47% and 47% respectively), with further decrease (80%) in T2DM, p<0.001. GDI was the major determinant of fasting and 2-hr glucose level.

Conclusions: Obese adolescents who show signs of glucose dysregulation, including abnormal fasting glucose, glucose intolerance or both, are more likely to have impaired insulin secretion than reduced insulin sensitivity. Given the impairment in insulin secretion, they are at high risk for progression to type 2 diabetes. Further deterioration in insulin sensitivity or secretion may enhance the risk for this progression.