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Title: HbA(1c) diagnostic categories and beta-cell function relative to insulin sensitivity in overweight/obese adolescents

Author
item SJAARDA, LINDSEY - University Of Pittsburgh Medical Center
item MICHALISZYN, SARA - University Of Pittsburgh Medical Center
item LEE, SOJUNG - University Of Pittsburgh Medical Center
item TFAYLI, HALA - American University Of Beirut
item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item FARCHOUKH, LAMA - University Of Pittsburgh Medical Center
item ARSLANIAN, SILVA - University Of Pittsburgh Medical Center

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/21/2012
Publication Date: 12/1/2012
Citation: Sjaarda, L.A., Michaliszyn, S.F., Lee, S., Tfayli, H., Bacha, F., Farchoukh, L., Arslanian, S.A. 2012. HbA(1c) diagnostic categories and beta-cell function relative to insulin sensitivity in overweight/obese adolescents. Diabetes Care. 35(12):2559-2563.

Interpretive Summary: HbA(1c) is a test used to estimate the levels of sugar in the body and to follow the effect of treatment in individuals with diabetes. There are new guidelines in adults to use HbA(1c) to diagnose diabetes (HbA(1c) >6.5%) and prediabetes (HbA(1c) 5.7 to <6.5%). The utility of the new cutoffs in pediatrics is not clear. We studied 160 overweight/obese adolescents with prediabetes (HbA(1c) 5.7 to <6.5%) and 44 adolescents with normal HbA(1c) (<5.7%). We found that overweight/obese adolescents with HbA(1c) in the at-risk/prediabetes category demonstrate markers for heightened risk of type 2 diabetes. Therefore, HbA(1c) is a suitable screening tool in large-scale studies examining the progression or reversal of type 2 diabetes risk in children.

Technical Abstract: 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 (HbA(1c) 5.7 to ,6.5%). We compared in vivo hepatic and peripheral insulin sensitivity by [6,6-2H2] glucose and a 3-h hyperinsulinemic-euglycemic clamp and beta-cell function by a 2-h hyperglycemic clamp (approximately 225 mg/dL) in overweight/obese (BMI >/= 85th percentile) adolescents with prediabetes (HbA(1c) 5.7 to <6.5%) (n = 160) to those with normal HbA1c (<5.7%) (n = 44). Beta-cell function was expressed relative to insulin sensitivity (i.e., the disposition index = insulin sensitivity x first-phase insulin). 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 beta-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(1c) category and 41% in the prediabetes HbA(1c) category had dysglycemia (impaired fasting glucose and/or impaired glucose tolerance) by a 2-h OGTT. Overweight/obese adolescents with HbA(1c) in the at-risk/prediabetes category demonstrate impaired beta-cell function relative to insulin sensitivity, a metabolic marker for heightened risk of type 2 diabetes. Thus, HbA(1c) may be a suitable screening tool in large-scale epidemiological observational and/interventional studies examining the progession or reversal of type 2 diabetes risk.