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
Authors: Sam Susan , Edelstein Sharon L. , Arslanian Silva A. , Barengolts Elena , Buchanan Thomas A. , Caprio Sonia , Ehrmann David A. , Hannon Tamara S. , Tjaden Ashley Hogan , Kahn Steven E. , Mather Kieren J. , Tripputi Mark , Utzschneider Kristina M. , Xiang Anny H. , Nadeau Kristen J. ,   RISE Consortium, Ehrmann David A. , Temple Karla A. , Rue Abby , Barengolts Elena , Mokhlesi Babak , Van Cauter Eve , Sam Susan , Miller M. Annette , Kahn Steven E. , Atkinson Karen M. , Palmer Jerry P. , Utzschneider Kristina M. , Gebremedhin Tsige , Kernan-Schloss Abigail , Kozedub Alexandra , Montgomery Brenda K. , Morse Emily J. , Mather Kieren J. , Garrett Tammy , Hannon Tamara S. , Lteif Amale , Patel Aniket , Chisholm Robin , Moore Karen , Pirics Vivian , Pratt Linda , Nadeau Kristen J. , Gross Susan , Zeitler Philip S. , Williams Jayne , Cree-Green Melanie , GarciaReyes Yesenia , Vissat Krista , Arslanian Silva A. , Brown Kathleen , Guerra Nancy , Porter Kristin , Caprio Sonia , Savoye Mary , Pierpont Bridget , Buchanan Thomas A. , Xiang Anny H. , Trigo Enrique , Beale Elizabeth , Hendee Fadi N. , Katkhouda Namir , Nayak Krishan , Martinez Mayra , Montgomery Cortney , Wang Xinhui , Edelstein Sharon L. , Lachin John M. , Hogan Ashley N. , Marcovina Santica , Harting Jessica , Albers John , Hill Dave , Savage Peter J. , Leschek Ellen W. 
Published: June 2021

OBJECTIVETo 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.RESEARCH DESIGN AND METHODSA 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 (HbA1c increase ≥0.5% from baseline).RESULTSGlycemic worsening occurred in 17.8% of youth versus 7.5% of adults at month 12 (P = 0.008) and in 36% of youth versus 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 versus placebo (hazard ratio 0.21, 95% 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 &lt; 0.01). Lower baseline OGTT-derived β-cell responses predicted month 21 worsening (P &lt; 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 &lt; 0.05). In adults, lower clamp- and OGTT-derived insulin sensitivity predicted month 12 and month 21 worsening (P &lt; 0.05).CONCLUSIONSGlycemic 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.