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

Abstract

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 β-cell function (βCF) in youth versus adults with impaired glucose tolerance or recently diagnosed type 2 diabetes.RESEARCH DESIGN AND METHODSThis 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 βCF at baseline and the change in glucose response curves 12 months after randomization were assessed.RESULTSAt randomization, the prevalence of the BPh curve was significantly higher in youth than adults (18.8% vs. 8.2%), with no differences in MPh or IIn. IS did not differ across glucose response curves in youth or adults. However, irrespective of curve type, youth had lower IS than adults (P < 0.05). βCF was lowest in IIn versus MPh and BPh in youth and adults (P < 0.05), yet compared with adults, youth had higher βCF 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.CONCLUSIONSDespite 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 β-cell hypersecretion in youth was not present in the IIn curve, emphasizing the severity of β-cell dysfunction in youth with this least favorable glucose response curve.

Trial registration: ClinicalTrials.gov NCT01779362 NCT01779375 NCT01763346.

Figure 1

Glucose (A), C-peptide (B), and insulin (C) concentrations by OGTT glucose response curves at randomization in youth (solid lines) and adult (dashed lines) RISE participants. Data are mean ± SE (upper or lower bar).

Figure 2

Box plots for M/I (A) and β-cell responses ACPRg (B), ACPRmax (C), and SSCP (D) by OGTT glucose response curves in youth and adults. P values from models evaluating the difference between youth and adults within each OGTT glucose response curve in adjusted models for IS (except for M/I), sex, race/ethnicity, and waist circumference.