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
Research Design and Methods: This was both a cross-sectional and 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-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). bCF was lowest in IIn vs. 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 curves. 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 2-fold 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.