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. 2009 Jan;32(1):100-5.
doi: 10.2337/dc08-1030. Epub 2008 Oct 3.

In vivo insulin sensitivity and secretion in obese youth: what are the differences between normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes?

Fida Bacha  1 , Neslihan Gungor, SoJung Lee, Silva A Arslanian
Affiliations

In vivo insulin sensitivity and secretion in obese youth: what are the differences between normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes?

Fida Bacha et al. Diabetes Care. 2009 Jan.

Abstract

Objective: Impaired glucose tolerance (IGT) represents a pre-diabetic 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 with those with normal glucose tolerance (NGT) and type 2 diabetes.

Research design and methods: A total of 12 obese adolescents with NGT, 19 with IGT, and 17 with type 2 diabetes underwent evaluation of insulin sensitivity (3-h hyperinsulinemic [80 micro/m(2)/min]-euglycemic clamp), first-phase insulin and second-phase insulin secretion (2-h hyperglycemic clamp), body composition, and abdominal adiposity. Glucose disposition index (GDI) was calculated as the product of first-phase insulin x insulin sensitivity.

Results: Insulin-stimulated glucose disposal was significantly lower in subjects with type 2 diabetes compared with subjects with NGT and IGT, with no difference between the latter two. However, compared with youth with NGT, youth with IGT have significantly lower first-phase insulin and C-peptide levels and GDI (P = 0.012), whereas youth with type 2 diabetes have an additional defect in second-phase insulin. Fasting and 2-h glucose correlated with GDI (r = -0.68, P < 0.001 and r = -0.73, P < 0.001, respectively) and first-phase insulin but not with insulin sensitivity.

Conclusions: Compared with youth with NGT, obese adolescents with IGT have evidence of a beta-cell defect manifested in impaired first-phase insulin secretion, with a more profound defect in type 2 diabetes involving both first- and second-phase insulin. GDI shows a significantly declining pattern: it is highest in NGT, intermediate in IGT, and lowest in type 2 diabetes. Such data suggest that measures to prevent progression or conversion from pre-diabetes to type 2 diabetes should target improvement in beta-cell function.

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Figures

Figure 1
Figure 1
A: Insulin-stimulated total, oxidative, and nonoxidative glucose disposal in NGT (□), IGT (formula image), and type 2 diabetes (▪). B: First and second-phase insulin levels in NGT (▵), IGT (formula image), and type 2 diabetes (•). C: Glucose disposition index in NGT, IGT, and type 2 diabetes. Error bars reflect SEs.
Figure 2
Figure 2
Relation of first-phase insulin and GDI to the 2-h glucose during the OGTT in NGT (▵), IGT (formula image), and type 2 diabetes (•).
See this image and copyright information in PMC

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