Metabolic abnormalities underlying the different prediabetic phenotypes in obese adolescents

Anna M G Cali', Riccardo C Bonadonna, Maddalena Trombetta, Ram Weiss, Sonia Caprio, Anna M G Cali', Riccardo C Bonadonna, Maddalena Trombetta, Ram Weiss, Sonia Caprio

Abstract

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-euglycemic and hyperglycemic clamps), applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration, in 40 normal glucose tolerance (NGT), 17 IFG, 23 IGT, and 11 IFG/IGT obese adolescents. Percent fat (by dual-energy x-ray absorptiometry), age, gender and ethnicity were comparable among groups.

Results: Peripheral insulin sensitivity was similar between the IFG and NGT groups. In contrast, the IGT and IFG/IGT groups showed marked reductions in peripheral insulin sensitivity (P < 0.002). Basal hepatic insulin resistance index (basal hepatic glucose production x fasting plasma insulin) was significantly increased in IFG, IGT, and IFG/IGT (P < 0.009) compared with 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 r(2) = 25.9%).

Conclusions: IFG, in obese adolescents, is linked primarily to alterations in glucose sensitivity of first-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.

Figures

Figure 1
Figure 1
A, BSR. B, Glucose sensitivity of first-phase insulin secretion (σ1); *, P = 0.004 IFG vs. NGT; *, P = 0.04 IGT vs. NGT; *, P = 0.0001 IFG/IGT vs. NGT adolescents. C, Glucose sensitivity of second-phase insulin secretion (σ2). D, Glucose clearance; *, P = 0.02 IGT vs. NGT.

Source: PubMed

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