In Vivo Insulin Sensitivity and Secretion in Obese Youth: What are the Differences between NGT, IGT and Type 2 Diabetes?

Abstract

Objective: Impaired glucose tolerance (IGT) represents a prediabetic state. Controversy continues in regards to its pathophysiology. The aim of this study was to investigate the differences in insulin sensitivity (IS) and secretion in obese adolescents with IGT, compared to those with normal glucose tolerance (NGT) and type 2 diabetes (T2DM).

Research Design and Methods: Twelve obese adolescents with NGT, 19 with IGT and 17 with T2DM underwent evaluation of IS (3-hr hyperinsulinemic (80mu/m²/min)–euglycemic clamp), 1^st and 2^nd phase insulin (1^stPI, 2^ndPI) secretion (2-hr hyperglycemic clamp); body composition and abdominal adiposity. Glucose disposition index (GDI) was calculated as the product of 1^st PI x IS.

Results: Insulin-stimulated glucose disposal was significantly lower in T2DM compared with NGT and IGT with no difference between the latter two. However, compared with NGT, youth with IGT have significantly lower 1^st PI and C-peptide levels, and lower GDI (p=0.012) while youth with T2DM have an additional defect in 2^nd PI. Fasting and 2-hr glucose correlated with GDI (r=−0.68, p<0.001 and r=−0.73, p<0.001) and 1^st PI but not with IS.

Conclusion: Compared with NGT youth, obese adolescents with IGT have evidence of β-cell defect manifested in impaired 1^st PI secretion with a more profound defect in T2DM involving both 1^st and 2^nd PI. GDI shows a significantly declining pattern, highest in NGT, intermediate in IGT and lowest in T2DM. Such data suggest that measures to prevent progression or conversion from pre-diabetes to T2DM should target improvement in β-cell function.