Resumen de HbA^sub 1c^ Diagnostic Categories and [Beta]-Cell Function Relative to Insulin Sensitivity in Overweight/Obese Adolescents
Lindsey A. Sjaarda, Sara F. Michahszyn, Sojung Lee, Hala Tfayli, Fida Bacha, Lama Farchoukh, Silva Arslanian
The recommended HbA^sub 1c^ 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 (HbA^sub 1c^ 5.7 to <6.5%). We compared in vivo hepatic and peripheral insulin sensitivity by [6,6-^sup 2^H^sub 2^] glucose and a 3-h hyperinsulinemic-euglycemic clamp and ?-cell function by a 2-h hyperglycemic clamp (~225 mg/dL) in overweight/obese (BMI ?85th percentile) adolescents with prediabetes (HbA^sub 1c^ 5.7 to <6.5%) (n = 160) to those with normal HbA^sub 1c^ (<5.7%) (n = 44). ?-Cell function was expressed relative to insulin sensitivity (i.e., the disposition index = insulin sensitivity × first-phase insulin). In the prediabetes versus normal HbA^sub 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 ?-cell function relative to insulin sensitivity was lower (366 ± 48 vs. 524 ± 25 mg/kg/min; P = 0.005). A total of 27% of youth in the normal HbA^sub 1c^ category and 41% in the prediabetes HbA^sub 1c^ category had dysglycemia (impaired fasting glucose and/or impaired glucose tolerance) by a 2-h OGTT. Overweight/obese adolescents with HbA^sub 1c^ in the at-risk/prediabetes category demonstrate impaired ?-cell function relative to insulin sensitivity, a metabolic marker for heightened risk of type 2 diabetes. Thus, HbA^sub 1c^ 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. [PUBLICATION ABSTRACT]
