Baseline Predictors of Glycemic Worsening in Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes in the Restoring Insulin Secretion (RISE) Study.

Abstract

To identify predictors of glycemic worsening among youth and adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes in the Restoring Insulin Secretion (RISE) Study. A total of 91 youth (10-19 years) were randomized 1:1 to 12 months of metformin (MET) or 3 months of glargine, followed by 9 months of metformin (G-MET), and 267 adults were randomized to MET, G-MET, liraglutide plus MET (LIRA+MET), or placebo for 12 months. All participants underwent a baseline hyperglycemic clamp and a 3-h oral glucose tolerance test (OGTT) at baseline, month 6, month 12, and off treatment at month 15 and month 21. Cox models identified baseline predictors of glycemic worsening (HbA_1c increase ≥0.5% from baseline). Glycemic worsening occurred in 17.8% of youth versus 7.5% of adults at month 12 (<i>P</i> = 0.008) and in 36% of youth versus 20% of adults at month 21 (<i>P</i> = 0.002). In youth, glycemic worsening did not differ by treatment. In adults, month 12 glycemic worsening was less on LIRA+MET versus placebo (hazard ratio 0.21, 95% CI 0.05-0.96, <i>P</i> = 0.044). In both age-groups, lower baseline clamp-derived β-cell responses predicted month 12 and month 21 glycemic worsening (<i>P</i> < 0.01). Lower baseline OGTT-derived β-cell responses predicted month 21 worsening (<i>P</i> < 0.05). In youth, higher baseline HbA_1c and 2-h glucose predicted month 12 and month 21 glycemic worsening, and higher fasting glucose predicted month 21 worsening (<i>P</i> < 0.05). In adults, lower clamp- and OGTT-derived insulin sensitivity predicted month 12 and month 21 worsening (<i>P</i> < 0.05). Glycemic worsening was more common among youth than adults with IGT or recently diagnosed type 2 diabetes, predicted by lower baseline β-cell responses in both groups, hyperglycemia in youth, and insulin resistance in adults.