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Wisconsin Epidemiologic Study of Diabetic Retinopathy

Barbara E. K. Klein, MD; Ronald Klein, MD; Patrick E. McBride, MD; Karen J. Cruickshanks, PhD; Mari Palta, PhD; Michael D. Knudtson, MS; Scot E. Moss, MA; Jennifer O. Reinke, BA

Arch Intern Med. 2004;164:1917-1924.

Background  Diabetic retinopathy and proteinuria, manifestations of microvascular abnormalities, occur early in the course of diabetes mellitus; in contrast, macrovascular cardiovascular complications usually occur later. Retinal vessel characteristics may be informative about risk of cardiovascular disease in persons with diabetes. We evaluated this in a longitudinal cohort study of persons with type 1 diabetes.

Methods  The population consisted of persons with type 1 diabetes who were receiving care in 11 counties in Wisconsin. Subjects (n = 996) were examined at baseline (1980-1982), and 4, 10, 14, and 20 years later. Evaluations included medical history and measurements of height, weight, blood pressure, and glycosylated hemoglobin. Fundus photographs were graded for diabetic retinopathy at baseline, and the same photographs were graded later for the diameters of retinal blood vessels. At each examination, a history of cardiovascular disease events since the last examination (and prior to baseline) was obtained. Mortality was monitored yearly.

Results  The 20-year age-adjusted cumulative incidences were 18.1% for angina, 14.8% for myocardial infarction, and 5.9% for stroke. Severity of diabetic retinopathy was associated with angina and stroke. Arteriovenous ratio was associated with myocardial infarction. Of 273 deaths, 176 involved heart disease. The severity of retinopathy and arteriovenous ratio was associated with heart disease mortality. Nephropathy was more informative about the cardiovascular end points than were the blood vessel characteristics.

Conclusions  Incidences of cardiovascular disease, including mortality, were common in people with type 1 diabetes during a 20-year interval. Retinal vascular characteristics were associated with these end points, but this association was confounded by nephropathy.

From the Departments of Ophthalmology and Visual Sciences (Drs B. E. K. Klein, R. Klein, and Cruickshanks, Messrs Knudtson and Moss, and Ms Reinke), Medicine (Dr McBride), and Population Health Sciences (Drs Cruickshanks and Palta), University of Wisconsin Medical School, Madison. Dr McBride has received honoraria from GlaxoSmithKline, Bristol-Myers Squibb Co, Kos Pharmaceuticals Inc, Merck & Co Inc, and Pfizer Inc.

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