American Diabetes Association
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Risk factors for the development of retinopathy in pre-diabetes and type 2 diabetes: The Diabetes Prevention Program experience

posted on 2022-09-26, 14:19 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 DPPOS Research Group



To determine glycemic and non-glycemic risk factors that contribute to the presence of diabetic retinopathy (DR) before and after the onset of type 2 diabetes (T2D).


During the Diabetes Prevention Program (DPP) and DPP Outcome Study (DPPOS), we performed fundus photography over time on adults at high risk to develop T2D, including after they developed diabetes. Fundus photographs were graded using the ETDRS grading system with DR defined as typical lesions of DR (microaneurysms, exudates or hemorrhage, or worse) in either eye.


By DPPOS year 16 (approximately 20 years after randomization into DPP), 24% of 1,614 who had developed T2D and 14% of 885 who remained non-diabetic had DR. In univariate analyses, utilizing results from across the entire duration of follow-up, American Indian race was associated with less frequent DR compared to Non-Hispanic Whites (NHW), and higher HbA1c, fasting and 2-hour plasma glucose levels during an oral glucose tolerance test, weight, and history of hypertension, dyslipidemia and smoking, but not treatment group assignment, were associated with more frequent DR. On multivariate analysis, American Indian race was associated with less DR compared to NHW (OR = 0.36; 95% CI: 0.20-0.66) and average HbA1c was associated with more DR (OR = 1.92; 95% CI: 1.46-1.74 per SD [0.7%] increase in HbA1c).


DR may occur in adults with prediabetes and early in the course of T2D. HbA1c was an important risk factor for the development of DR across the entire glycemic range from prediabetes to T2D. 


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