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The Effect of Interventions to Prevent Type 2 Diabetes on the Development of Diabetic Retinopathy: The DPP/DPPOS Experience

posted on 25.05.2022, 19:00 authored by Neil H. White, Qing Pan, William C. Knowler, Emily B. Schroeder, Dana Dabelea, Emily Y. Chew, Barbara Blodi, Ronald B. Goldberg, Xavier Pi-Sunyer, Christine Darwin, Mathias Schlögl, David M. Nathan, the Diabetes Prevention Program Research Group



To determine whether interventions that slow or prevent the development of type 2 diabetes mellitus in those at risk reduce the subsequent prevalence of diabetic retinopathy. 


The Diabetes Prevention Program (DPP) randomized subjects at risk for developing type 2 diabetes because of overweight/obesity and dysglycemia to either metformin (MET), intensive lifestyle intervention (ILS) or placebo (PLB) to assess the prevention of diabetes. During the DPP and DPP Outcome Study (DPPOS), we performed fundus photography over time on study participants, regardless of their diabetes status. Fundus photographs were graded using the ETDRS grading system with diabetic retinopathy defined as typical lesions of diabetic retinopathy (microaneurysms, exudates or hemorrhage, or worse) in either eye.


Despite reduced progression to diabetes in the ILS and MET groups compared to PLB, there was no difference in the prevalence of diabetic retinopathy between treatment groups after 1, 5, 11 or 16 years of follow up. No treatment group differences in retinopathy were found within prespecified subgroups (baseline age, sex, race/ethnicity, baseline BMI). In addition, there was no difference in the prevalence of diabetic retinopathy between those exposed to metformin and those not exposed to metformin regardless of treatment group assignment.


Interventions that delay or prevent the onset of type 2 diabetes in overweight/obese subjects with dysglycemia who are at risk for diabetes do not reduce the development of diabetic retinopathy for up to 20 years.


Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under award numbers U01 DK048489, U01 DK048339, U01 DK048377, U01 DK048349, U01 DK048381, U01 DK048468, U01 DK048434, U01 DK048485, U01 DK048375, U01 DK048514, U01 DK048437, U01 DK048413, U01 DK048411, U01 DK048406, U01 DK048380, U01 DK048397, U01 DK048412, U01 DK048404, U01 DK048387, U01 DK048407, U01 DK048443, and U01 DK048400, by providing funding during DPP and DPPOS to the clinical centers and the Coordinating Center for the design and conduct of the study, and collection, management, analysis, and interpretation of the data. Funding was also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart Lung and Blood Institute, the National Cancer Institute, the Office of Research on Women’s Health, the National Institute on Minority Health and Health Disparities, the Centers for Disease Control and Prevention, and the American Diabetes Association. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Merck KGaA provided medication for DPPOS. DPP/DPPOS have also received donated materials, equipment, or medicines for concomitant conditions from Bristol-Myers Squibb, Parke-Davis, and LifeScan Inc., Health O Meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care, Inc., Merck and Co., Nike Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. McKesson BioService