HbA1c Diagnostic Categories and β-Cell Function Relative to Insulin Sensitivity in Overweight/Obese Adolescents
- Lindsey A. Sjaarda, PHD1,
- Sara F. Michaliszyn, PHD1,
- SoJung Lee, PHD1,
- Hala Tfayli, MD3,
- Fida Bacha, MD4,
- Lama Farchoukh, MD1 and
- Silva A. Arslanian, MD1,2⇓
- 1Division of Weight Management and Wellness, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
- 2Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
- 3Department of Pediatrics and Adolescent Medicine, Pediatric Endocrinology, American University of Beirut, Beirut, Lebanon
- 4Department of Pediatrics, Baylor College of Medicine, Houston, Texas
- Corresponding author: Silva A. Arslanian, .
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 <6.5%).
RESEARCH DESIGN AND METHODS We compared in vivo hepatic and peripheral insulin sensitivity by [6,6-2H2] 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 <6.5%) (n = 160) to those with normal HbA1c (<5.7%) (n = 44). β-Cell function was expressed relative to insulin sensitivity (i.e., the disposition index = insulin sensitivity × first-phase insulin).
RESULTS In the prediabetes versus normal HbA1c 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 27% of youth in the normal HbA1c category and 41% 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.
- Received April 19, 2012.
- Accepted June 21, 2012.
- © 2012 by the American Diabetes Association.
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