Abstract

Obese adolescent girls are at increased risk for type 2 diabetes, characterized by defects in insulin secretion and action. We sought to determine if later glucose peak timing (>30 minutes), 1-hour glucose >155 mg/dl, or monophasic pattern of glucose excursion during an oral glucose tolerance test (OGTT) reflect a worse cardiometabolic risk profile. Post-pubertal overweight/obese adolescent girls without diabetes were studied (N = 88; age, 15.2 ± 0.2 years; body mass index percentile, 97.7 ± 0.5). All participants completed an OGTT and body composition measures. Thirty-two girls had a four-phase hyperinsulinemic euglycemic clamp with isotope tracers, vascular imaging, and muscle mitochondrial assessments. Participants were categorized by glucose peak timing (≤30 min = early; >30 min = late), 1-hour glucose concentration (±155 mg/dL) and glucose pattern (monophasic, biphasic). Girls with a late (N = 54) vs earlier peak (n = 34) timing had higher peak glucose (P < 0.001) and insulin (P = 0.023), HbA1c (P = 0.021); prevalence of hepatic steatosis (62% vs 26%; P = 0.003) and lower oral disposition index (P < 0.001) and glucagon-like peptide-1 response (P = 0.037). When classified by 1-hour glucose, group differences were similar to peak timing, but minimal when classified by glucose pattern. In the >155 mg/dL group only, peripheral insulin sensitivity and fasting free fatty acids were worse. A later glucose peak or >155 mg/dL 1-hour glucose predicts metabolic disease risk in obese adolescent girls. This may defect incretin effects and first phase insulin response, and muscle and adipose insulin resistance.

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