Objective. The aim of this study was to define the metabolic abnormalities underlying the prediabetic status of Isolated Impaired Fasting Glucose (IFG), Isolated Impaired Glucose Tolerance (IGT), and Combined (IFG/IGT) in obese youth.

Research Design and Methods. We used state-of-the-art techniques (hyperinsulinemic-euglycaemic and hyperglycaemic clamps), applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration, in 40 NGT, 17 IFG, 23 IGT and 11 IFG+IGT obese adolescents. % fat (DEXA), age, gender and ethnicity were comparable among groups.

Results. Peripheral insulin sensitivity was similar between IFG and NGT group. In contrast, the IGT and IFG/IGT groups showed marked reductions in peripheral insulin sensitivity (P<0.002). Basal hepatic insulin resistance index (HGP\xFPI) significantly increased in IFG, IGT and IFG/IGT respectively (p<0.009) compared to NGT. Glucose sensitivity of first phase insulin secretion was progressively lower in IFG, IGT and IFG/IGT compared with NGT. Glucose sensitivity of second phase secretion showed a statistically significant defect only in the IFG/IGT group. In a multivariate regression analysis, glucose sensitivity of first phase secretion and basal insulin secretion rate were significant independent predictors of FPG (total r²: 25.9%).

Conclusions. IFG, in obese adolescents, is linked primarily to alterations in glucose sensitivity of 1^st phase insulin secretion and liver insulin sensitivity. The IGT group is affected by a more severe degree of peripheral insulin resistance and reduction in first phase secretion. IFG/IGT is hallmarked by a profound insulin resistance and by a new additional defect in second phase insulin secretion.