OGTT Glucose Response Curves, Insulin Sensitivity, and b-Cell Function in RISE: Comparison Between Youth and Adults at Randomization and in Response to Interventions to Preserve b-Cell Function

Abstract

OBJECTIVE We examined the glucose response curves (biphasic [BPh], monophasic [MPh], incessant increase [IIn]) during an oral glucose tolerance test (OGTT) and their relationship to insulin sensitivity (IS) and b-cell function (bCF) in youth versus adults with impaired glucose tolerance or recently diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS This was both a cross-sectional and a longitudinal evaluation of participants in the RISE study randomized to metformin alone for 12 months or glargine for 3 months followed by metformin for 9 months. At baseline/randomization, OGTTs (85 youth, 353 adults) were categorized as BPh, MPh, or IIn. The relationship of the glucose response curves to hyperglycemic clamp–measured IS and bCF at baseline and the change in glucose response curves 12 months after randomization were assessed. RESULTS At randomization, the prevalence of the BPh curvewas significantly higher inyouth than adults (18.8% vs. 8.2%), with no differences in MPh or IIn. IS did not differ across glucose responsecurves inyouthor adults. However, irrespectiveof curvetype, youthhadlower IS than adults (P < 0.05). bCF was lowest in IIn versus MPh and BPh in youth and adults (P < 0.05), yet compared with adults, youth had higher bCF in BPh and MPh (P < 0.005) but not IIn. At month 12, the change in glucose response curves did not differ between youth and adults, and there was no treatment effect. CONCLUSIONS Despite a twofold higher prevalence of the more favorable BPh curve in youth at randomization, RISE interventions did not result in beneficial changes in glucose response curves in youth compared with adults. Moreover, the typical b-cell hypersecretion in youth was not present in the IIn curve, emphasizing the severity of b-cell dysfunction in youth with this least favorable glucose response curve.