American Diabetes Association
99_Supplemental Tables_Appendix_GRADE Research Group_04.30.21_2_CLEAN.pdf (362.25 kB)

Clinical and Metabolic Characterization of Adults with Type 2 Diabetes by Age in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study Cohort

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Version 2 2022-06-23, 18:28
Version 1 2022-06-13, 15:57
posted on 2022-06-23, 18:28 authored by Vanita R. Aroda, Heidi Krause-Steinrauf, Erin J. Kazemi, John B. Buse, Barbara I. Gulanski, Hermes J. Florez, Andrew J. Ahmann, Amy Loveland, Alexander Kuhn, Jacqueline Y. Lonier, Deborah J Wexler, the GRADE Research Group

Objective: Differences in type 2 diabetes phenotype by age are described, but it is not known whether these differences are seen in a more uniformly defined adult population at a common early stage of care. We characterize age-related clinical and metabolic characteristics of adults with type 2 diabetes on metformin monotherapy, prior to treatment intensification. 

Research Design and Methods: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study enrolled participants with type 2 diabetes duration <10 years, A1c 6.8-8.5%, on metformin monotherapy, and randomly assigned to one of four additional glucose-lowering medications. We compared baseline clinical and metabolic characteristics across age categories (<45; 45-<55; 55-<65; 65 years) using ANOVA and Pearson’s chi-squared tests.. 

Results: Within the GRADE cohort (n=5,047), we observed significant differences by age with younger adults having greater racial diversity, fewer medications for common comorbidities, lower prevalence of CVD, higher weight and BMI, more pronounced hyperglycemia and diabetic dyslipidemia, with metabolic profile indicating lower insulin sensitivity (1/fasting insulin, HOMA-2S, Matsuda index) and inadequate β cell response (oral disposition index) (p < 0.05 across age categories). 

Conclusions: Clinical and metabolic characteristics of type 2 diabetes differ by age within the GRADE cohort. Younger adults exhibit more prominent obesity-related characteristics, including higher obesity levels, lower insulin sensitivity and beta cell compensation. Given the increasing burden of type 2 diabetes and complications, particularly among younger populations, these age-related distinctions may inform risk factor management approaches and treatment priorities. Further study will determine whether age-related differences impact response to therapy. 


The GRADE Study is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health under Award Number U01DK098246. The planning of GRADE was supported by a U34 planning grant from the NIDDK (U34-DK-088043). The American Diabetes Association supported the initial planning meeting for the U34 proposal. The National Heart, Lung, and Blood Institute and the Centers for Disease Control and Prevention also provided funding support. The Department of Veterans Affairs provided resources and facilities. Additional support was provided by grant numbers P30 DK017047, P30 DK020541-44, P30 DK020572, P30 DK072476, P30 DK079626, P30 DK092926 , U54 GM104940, UL1 TR000439, UL1 TR000445, UL1 TR001108, UL1 TR001409, UL1 TR001449, UL1 TR002243, UL1 TR002345, UL1 TR002378, UL1 TR002489, UL1 TR002529, UL1 TR002535, UL1 TR002537, UL1 TR001425 and UL1 TR002548. Educational materials have been provided by the National Diabetes Education Program. Material support in the form of donated medications and supplies has been provided by Becton, Dickinson and Company, Bristol-Myers Squibb, Merck, NovoNordisk, Roche Diagnostics, and Sanofi. The content of this manuscript 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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