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
Research Design and Methods: Ninety-one 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); 267 adults to MET, G-MET, liraglutide plus MET (LIRA+MET) or placebo for 12 months. All participants underwent baseline hyperglycemic clamp and 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 (HbA1c increase ≥0.5% from baseline).
Results: Glycemic worsening occurred in 17.8% of youth vs. 7.5% of adults at month-12 (p=0.008), and 36% of youth vs. 20% of adults at month-21 (p=0.002). In youth, glycemic worsening did not differ by treatment. In adults, month-12 glycemic worsening was less on LIRA+MET vs. placebo (HR 0.21, CI 0.05-0.96, p=0.044). In both age groups, lower baseline clamp-derived β-cell responses predicted month-12 and month-21 glycemic worsening (p<0.01); lower baseline OGTT-derived β-cell responses predicted month-21 worsening (p<0.05). In youth, higher baseline HbA1c and 2-h glucose predicted month-12 and month-21 glycemic worsening and higher fasting glucose predicted month-21 worsening (p<0.05). In adults, lower clamp and OGTT-derived insulin sensitivity predicted month-12 and month-21 worsening (p<0.05).
Conclusions: 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.