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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

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posted on 15.06.2021, 19:25 by Susan Sam, Sharon L. Edelstein, Silva A. Arslanian, Elena Barengolts, Thomas A. Buchanan, Sonia Caprio, David A. Ehrmann, Tamara S. Hannon, Ashley Hogan Tjaden, Steven E. Kahn, Kieren J. Mather, Mark Tripputi, Kristina M. Utzschneider, Anny H. Xiang, Kristen J. Nadeau, The RISE Consortium
Objective: Identify predictors of glycemic worsening among youth and adults with impaired glucose tolerance (IGT) or recently-diagnosed type 2 diabetes in the 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.

Funding

RISE is supported by grants from the National Institutes of Health (U01DK-094406, U01DK-094430, U01DK-094431, U01DK-094438, U01DK-094467, P30DK-017047, P30DK-020595, P30DK-045735, P30DK-097512, UL1TR-000430, UL1TR-001082, UL1TR-001108, UL1TR-001855, UL1TR-001857, UL1TR-001858, UL1TR-001863), the Department of Veterans Affairs, and Kaiser Permanente Southern California. Additional financial and material support from the American Diabetes Association, Allergan Corporation, Apollo Endosurgery, Abbott Laboratories, and Novo Nordisk A/S is gratefully acknowledged. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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