HbA(1c) diagnostic categories and β-cell function relative to insulin sensitivity in overweight/obese adolescents.
OBJECTIVE
The recommended HbA(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(1c) 5.7 to <6.5%).


METHODS
We compared in vivo hepatic and peripheral insulin sensitivity by [6,6-(2)H(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 (HbA(1c) 5.7 to <6.5%) (n = 160) to those with normal HbA(1c) (<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 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 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.


CONCLUSIONS
Overweight/obese adolescents with HbA(1c) 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, HbA(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.
Division of Weight Management and Wellness, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Lindsey A
LA
Sjaarda
Sara F
SF
Michaliszyn
SoJung
S
Lee
Hala
H
Tfayli
Fida
F
Bacha
Lama
L
Farchoukh
Silva A
SA
Arslanian
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000097:blood* / Q000503:physiopathology*; D050177:Overweight / Q000097:blood* / Q000503:physiopathology*; D055815:Young Adult
D001786:Blood Glucose; D006442:Glycated Hemoglobin