Risk Factors for the Development of Retinopathy in Prediabetes and Type 2 Diabetes: The Diabetes Prevention Program Experience
Neil H. White, Qing Pan, William C. Knowler, Emily B. Schroeder, Dana Dabelea, Emily Y. Chew, Barbara Blodi, Ronald Goldberg, F. Xavier Pi‐Sunyer, Christine Darwin, Mathias Schlögl, David M. Nathan, George A. Bray, Kishore M. Gadde, Iris W. Culbert, Jennifer Arceneaux, Annie Chatellier, Amber Dragg, Catherine M. Champagne, Crystal Duncan, Barbara Eberhardt, Frank L. Greenway, Fonda G. Guillory, April A. Herbert, Michael L. Jeffirs, Betty M. Kennedy, Erma Levy, Monica Lockett, Jennifer C. Lovejoy, Laura H. Morris, Lee E. Melancon, Donna H. Ryan, Deborah A. Sanford, Kenneth G. C. Smith, Lisa L. Smith, Julia A. St. Amant, Richard T. Tulley, Paula C. Vicknair, Donald S. Williamson, Jeffery J. Zachwieja, Kenneth S. Polonsky, Janet Tobian, David A. Ehrmann, Margaret J. Matulik, Karla A. Temple, Bart Clark, Kirsten Czech, Catherine DeSandre, Brittnie Dotson, Ruthanne Hilbrich, Wylie McNabb, Ann R. Semenske, Jose F. Caro, Kevin Furlong, Barry J. Goldstein, Pamela G. Watson, Kellie A. Smith, Jewel Mendoza, Marsha Simmons, Wendi Wildman, Renee Liberoni, John Spandorfer, Constance Pepe, Richard P. Donahue, Ronald Goldberg, Ronald J. Prineas, Jeanette Calles, Anna Giannella, Patricia M. Rowe, Juliet Sanguily, Paul Cassanova-Romero, Sumaya Castillo-Florez, Hermes Flórez, Rajesh Garg, Lascelles Kirby, Olga Lara, Carmen Larreal, Valerie McLymont, Jadell Mendez, Arlette Perry, Patrice G. Saab, Bertha Veciana, Steven M. Haffner, Helen P. Hazuda, Maria G. Montez, Kathy Hattaway, Juan Isaac, Carlos Lorenzo, Arlene Martinez, Monica Salazar, Tatiana Walker, Dana Dabelea, Richard F. Hamman, Patricia V. Nash, Sheila C. Steinke, Lisa Testaverde, Jennifer Truong, Denise Anderson, Larry B. Ballonoff, Alexis Bouffard
Abstract
OBJECTIVE: To determine glycemic and nonglycemic risk factors that contribute to the presence of diabetic retinopathy (DR) before and after the onset of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: During the Diabetes Prevention Program (DPP) and DPP Outcome Study (DPPOS), we performed fundus photography over time in adults at high risk for developing T2D, including after they developed diabetes. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study (ETDRS) grading system, with DR defined as typical lesions of DR (microaneurysms, exudates, hemorrhage, or worse) in either eye. RESULTS: By DPPOS year 16 (∼20 years after random assignment into DPP), 24% of 1,614 participants who had developed T2D and 14% of 885 who remained without diabetes had DR. In univariate analyses, using results from across the entire duration of follow-up, American Indian race was associated with less frequent DR compared with non-Hispanic White (NHW) race, and higher HbA1c, fasting and 2-h 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 with NHW (odds ratio [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). CONCLUSIONS: 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.