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. 2010 Oct;33(10):2225-31.
doi: 10.2337/dc10-0004. Epub 2010 Jun 30.

From pre-diabetes to type 2 diabetes in obese youth: pathophysiological characteristics along the spectrum of glucose dysregulation

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

From pre-diabetes to type 2 diabetes in obese youth: pathophysiological characteristics along the spectrum of glucose dysregulation

Fida Bacha et al. Diabetes Care. 2010 Oct.

Abstract

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

Research design and methods: A total of 24 obese adolescents with NGT, 13 with IFG, 29 with IGT, 11 with combined IFG/IGT, and 30 with type 2 diabetes underwent evaluation of hepatic glucose production ([6,6-(2)H(2)]glucose), insulin-stimulated glucose disposal (R(d), euglycemic clamp), first- and second-phase insulin secretion (hyperglycemic clamp), body composition (dual-energy X-ray absorptiometry), abdominal adiposity (computed tomography), and substrate oxidation (indirect calorimetry).

Results: Adolescents with NGT, pre-diabetes, and type 2 diabetes had similar body composition and abdominal fat distribution. R(d) was lower (P = 0.009) in adolescents with type 2 diabetes than in those with NGT. Compared with adolescents with NGT, first-phase insulin was lower in those with IFG, IGT, and IFG/IGT with further deterioration in those with type 2 diabetes (P < 0.001), and β-cell function relative to insulin sensitivity (glucose disposition index [GDI]) was also lower in those with IFG, IGT, and IFG/IGT (40, 47, and 47%, respectively), with a further decrease (80%) in those with type 2 diabetes (P < 0.001). GDI was the major determinant of fasting and 2-h glucose levels.

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 rather 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.

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Figures

Figure 1
Figure 1
A: Insulin-stimulated total, oxidative, and nonoxidative glucose disposal in subjects with NGT (open bars), IFG (dotted bars), IGT (striped bar), IFG/IGT (diamond bars), and type 2 diabetes (T2DM) (filled bars). P values are for trend (ANOVA P values). B: First- and second-phase insulin levels during the hyperglycemic clamp in NGT (○), IFG (♢), IGT (□), IFG/IGT (*), and type 2 diabetes (■). C: GDI in subjects with NGT (open bar), IFG (dotted bar), IGT (striped bar), IFG/IGT (diamond bar), and type 2 diabetes (filled bar). In A and C, letters are significant post hoc analysis (Bonferroni correction): P < 0.05 (a, type 2 diabetes versus NGT; b, type 2 diabetes versus IFG; c, type 2 diabetes versus IGT; e, NGT versus IFG/IGT; f, NGT versus IGT). Data are means ± SD.
Figure 2
Figure 2
Relationship of GDI to FPG (A) and 2-h OGTT glucose level (B) in NGT (○), IFG (♢), IGT (□), IFG/IGT (▲), and type 2 diabetes (■).
See this image and copyright information in PMC

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