Time to Glucose Peak during Oral Glucose Tolerance Test (OGTT) and Pathophysiological Biomarkers of Type 2 Diabetes in Obese Youth

Abstract

The time to glucose peak occurring at or after 30 min. during an OGTT identifies physiologically distinct groups of adults with differences in insulin sensitivity (IS) and secretion and risk of prediabetes and type 2 diabetes. We stratified 102 obese nondiabetic youth (age 15.0 ± 0.2 years; 49 M/53 F; 42 black/60 white) to Early-peak (EP) vs. Late-peak (LP) according to time to reach peak glucose (at 30 min. vs. >30 min.) during an OGTT and assessed the relationship to clamp-derived biomarkers of youth type 2 diabetes risk. Hepatic [[6,6-2H2]glucose] and peripheral IS [3-hour hyperinsulinemic (80 mu/m2/min)-euglycemic clamp], insulin secretion [2-hour hyperglycemic (225 mg/dL) clamp], β-cell function (BCF) relative to IS and body composition were compared. The LP group had lower hepatic and peripheral IS, lack of compensatory increase in 1st and 2nd phase insulin secretion and impaired BCF relative to IS compared with the EP group (Table), with similar fasting glucose and insulin, BMI percentiles and % body fat. In obese nondiabetic youth, the time to glucose peak during an OGTT reflects pathophysiological alterations associated with risk of type 2 diabetes. The risk imparted by a Late-peak glucose, independent of fasting glucose and insulin level, is mirrored in lower in vivo insulin sensitivity and impaired β-cell function, two major pathophysiologic biomarkers of youth type 2 diabetes.Variables, mean ± SEMEarly-peak (n=49)Late-peak (n=53)PGlycemic status (NGT/IGT), n (%)40 (82%) / 9 (18%)28 (53%) / 25 (47%)0.003Hepatic insulin sensitivity (mg/kg/min per µU/mL)-120.1 ± 1.714.5 ± 1.10.004Peripheral insulin sensitivity (mg/kg/min per µU/mL)2.55 ± 0.182.03 ± 0.150.0111st-phase insulin secretion (µU/mL)244.3 ± 26.7231.9 ± 26.7NSβ-cell function relative to insulin sensitivity (mg/kg/min)509.9 ± 45.3393.0 ± 33.40.026OGTT 2-hr glucose concentration (mg/dL)120.1 ± 2.8135.5 ± 3.40.001OGTT 2-hr insulin concentration (µU/mL)168.3 ± 22.0226.9 ± 21.80.010 Disclosure J. Kim: None. H. Tfayli: None. F. Bacha: Research Support; Self; AstraZeneca, JAEB Center For Health Research, National Institutes of Health, Pediatric Diabetes Consortium. S. Michaliszyn: None. S.A. Arslanian: None.