ESPE Abstracts (2015) 84 S6.3

From Obesity to Type 2 Diabetes

Silva Arslanian

Division of Weight Management and Wellness, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA

With the ever escalating trajectory of childhood obesity, rates of prediabetes and type 2 diabetes (T2DM) are on the incline. Impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) constitute a state of prediabetes with high risk for the development of T2DM. Among U.S. adolescents 12–19 years of age, NHANES 2005–2006, the prevalence of IFG, IGT and prediabetes was 13.1, 3.4 and 16.1%, respectively. Overweight adolescents had a 2.6-fold higher rate than those with normal weight.

Glucose homeostasis is maintained by a delicate balance between insulin sensitivity and insulin secretion and is best described by a hyperbolic function called the disposition index (DI). This relationship which is an expression of β-cell function relative to insulin sensitivity is a constant for a given glucose tolerance in any one individual. When insulin sensitivity declines, insulin secretion must increase to maintain glucose tolerance. Overweight and obesity are major contributors to the development of insulin resistance. In the presence of robust pancreatic β-cell compensatory insulin secretion, glucose homeostasis remains normal. When β-cells are no longer able to secrete sufficient insulin to overcome insulin resistance, prediabetes ensues progressing to T2D.

Cross-sectional and longitudinal studies in youth along the spectrum of dysglycemia from obese-NGT, to obese-IFG/IGT, to obese-T2DM, show that it is β-cell failure that results in prediabetes and T2DM. However even prior to reaching the universally accepted glycemic cut-points for the diagnosis of prediabetes, youth demonstrate declining β-cell function relative to insulin sensitivity along the continuum of what is considered to be normal fasting and normal 2-h glucose concentrations during an OGTT. Not only insulin secretion is impaired in prediabetes and T2DM but also there is impairment in incretin effect and glucagon secretion. Lastly, data re progression over time from NGT to IGT and from IGT to T2DM are highly variable, 9–24 and 0–20%, respectively.

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