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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Objective: Adolescents with polycystic ovary syndrome (PCOS) and obesity can have insulin resistance, dysglycemia, and hepatic steatosis. Excess pancreatic fat may disturb insulin secretion and relate to hepatic fat. Associations between pancreatic fat fraction (PFF) and metabolic measures in PCOS were unknown. Methods:This secondary analysis included 113 sedentary, nondiabetic adolescent girls (age = 15.4 [1.9] years), with or without PCOS and BMI ≥ 90th percentile.Participants underwent fasting labs, oral glucose tolerance tests, and magnetic resonance imaging for hepatic fat fraction (HFF) and PFF. Groups were categorized by PFF (above or below the median of 2.18%) and compared.Results: Visceral fat and HFF were elevated in individuals with PCOS versus control individuals, but PFF was similar. PFF did not correlate with serum androgens. Higher and lower PFF groups had similar HFF, with no correlation between PFF and HFF, although hepatic steatosis was more common in those with higher PFF (≥5.0% HFF; 60% vs. 36%; p = 0.014). The higher PFF group had higher fasting insulin (p = 0.026), fasting insulin resistance (homeostatic model assessment of insulin resistance, p = 0.032; 1/fasting insulin, p = 0.028), free fatty acids (p = 0.034), and triglycerides (p = 0.004) compared with those with lower PFF. β-Cell function and insulin sensitivity were similar between groups. Conclusions:Neither PCOS status nor androgens related to PFF. However, fasting insulin and postprandial lipids were worse with higher PFF.Data are presented as mean ± SD or median and interquartile range (25th, 75th). Impaired fasting glucose is >90 mg/dL. Impaired glucose tolerance is ≥140 mg/dL at 2 hours post glucose load in the OGTT. Prediabetes is HbA1c between 5.7% and 6.4% or impaired fasting glucose (glucose > 90 mg/dL) or impaired glucose tolerance (glucose ≥ 140 mg/dL at 2 hours post glucose load in the OGTT).Abbreviations: HbA1c, hemoglobin A1c; HOMA-IR, homeostatic model assessment of insulin resistance; ISSI-2, insulin secretion-sensitivity index-2; OMM, oral minimal model; PFF, pancreatic fat fraction; Si, insulin sensitivity; WBISI, whole-body insulin sensitivity index. a Excludes participants taking exenatide (n = 8).b n = 66.

Background/objective: Rates of dysglycemia are increasing in youth, secondary to obesity and decreased insulin sensitivity (IS) in puberty. The oral minimal model (OMM) has been developed in order to measure IS using an easy oral glucose load, such as an oral glucose tolerance test (OGTT), instead of an hyperinsulinemiceuglycemic clamp (HE-clamp), a more invasive and time-consuming procedure. However, this model, following a standard 2 hour-OGTT has never been validated in youth, a population known for a different physiologic response to OGTT than adults. Thus, we compared IS measurements obtained from OMM following a 2-hour OGTT to HE-clamp and isotope tracer-assessed tissue IS in adolescents. We also compared the liver/muscle-specific IS from HE-clamp with other liver/muscle-specific IS surrogates following an OGTT previously validated in adults. Methods: Secondary analysis of a cross-sectional study. Adolescent girls with (n = 26) and without (n = 7) polycystic ovary syndrome (PCOS) (14.6 ± 1.7 years; BMI percentile 23.3%-98.2%) underwent a 2-hour 75 g OGTT and a 4-phase HE-clamp. OMM IS (Si), dynamic Si (Si d) and other OGTT-derived muscle and liver IS indices were correlated with HE-clamp tissue-specific IS.