HbA1c diagnostic categories and β-cell function relative to insulin sensitivity in overweight-obese adolescents

Abstract

OBJECTIVE - The recommended HbA1c diagnostic categories remain controversial and their utility in doubt in pediatrics. We hypothesized that alterations in the pathophysiologic mechanisms of type 2 diabetes may be evident in the American Diabetes Association recommended at-risk-prediabetes category (HbA1c 5.7 to andlt;6.5percent). RESEARCH DESIGN AND METHODS - We compared in vivo hepatic and peripheral insulin sensitivity by [6,6-2H 2] glucose and a 3-h hyperinsulinemic-euglycemic clamp and β-cell function by a 2-h hyperglycemic clamp (∼225 mg-dL) in overweight-obese (BMI ≥85th percentile) adolescents with prediabetes (HbA1c 5.7 to andlt;6.5percent) (n = 160) to those with normal HbA 1c (andlt;5.7percent) (n = 44). β-Cell function was expressed relative to insulin sensitivity (i.e., the disposition index = insulin sensitivity X first-phase insulin). RESULTS - In the prediabetes versus normal HbA 1c category, fasting glucose, insulin, and oral glucose tolerance test (OGTT) area under the curve for glucose and insulin were significantly higher; hepatic and peripheral insulin sensitivity were lower; and β-cell function relative to insulin sensitivity was lower (366 ± 48 vs. 524 ± 25 mg-kg-min; P = 0.005). A total of 27percent of youth in the normal HbA1c category and 41percent in the prediabetes HbA1c category had dysglycemia (impaired fasting glucose and-or impaired glucose tolerance) by a 2-h OGTT. CONCLUSIONS - Overweight-obese adolescents with HbA1c in the at-risk-prediabetes category demonstrate impaired β-cell function relative to insulin sensitivity, a metabolic marker for heightened risk of type 2 diabetes. Thus, HbA1c may be a suitable screening tool in large-scale epidemiological observational and-or interventional studies examining the progression or reversal of type 2 diabetes risk. © 2012 by the American Diabetes Association.