Diabetes and Progression of Carotid Atherosclerosis The Insulin Resistance Atherosclerosis Study Lynne E. Wagenknecht, Daniel Zaccaro, Mark A. Espeland, Andrew J. Karter, Daniel H. O’Leary, Steven M. Haffner Objective—We sought to determine the rate of progression of carotid atherosclerosis in persons with normal glucose tolerance, impaired glucose tolerance, and undiagnosed and diagnosed type 2 diabetes. Methods and Results—The Insulin Resistance Atherosclerosis Study (IRAS) is an observational cohort study in which 1192 men and women were examined at a 5-year interval. Participants of 3 ethnic groups (non-Hispanic white, African American, and Hispanic) were selected from the general population to represent a range of glucose tolerance. Baseline and follow-up ultrasound studies were obtained to estimate progression of common carotid artery (CCA) and internal carotid artery (ICA) intimal-medial thickness (IMT). Baseline glucose tolerance status was defined by an oral glucose tolerance test and World Health Organization criteria. In persons with normal glucose tolerance, progression of CCA IMT was 3.8 m/y, and ICA IMT, 17.7 m/y. In both CCA and ICA, progression of IMT, unadjusted for cardiovascular disease (CVD) risk factors, was approximately twice the rate in persons with diabetes than in those with normal or impaired glucose tolerance. Adjustment for CVD risk factors attenuated these differences somewhat in both sites of the carotid artery. Persons with undiagnosed diabetes had a greater ICA IMT progression rate than did persons with diagnosed diabetes (33.9 m/y vs 26.6 m/y, P=NS). Progression rates did not differ between persons with normal and impaired glucose tolerance. Conclusions—Progression of carotid atherosclerosis is accelerated in persons with diabetes. Progression of ICA IMT is most pronounced in persons with undiagnosed diabetes. Early identification of diabetes and CVD risk factor control might reduce its atherosclerotic complications. (Arterioscler Thromb Vasc Biol. 2003;23:1035-1041.) Key Words: diabetes  atherosclerosis  epidemiology  prevention  ultrasound C ardiovascular disease (CVD) risk is increased 2- to-4- fold in persons with diabetes relative to those without. 1–3 Possible mechanisms for this increased risk include hyper- tension, dyslipidemia, hyperglycemia, and insulin resistance. Cross-sectional carotid artery intimal-medial thickness (IMT) is a powerful predictor of future CVD events. 4,5 Progression of IMT has also been shown to predict coronary events in men who have undergone coronary artery bypass graft surgery. 6 See page 917 We have reported previously, from a cross-sectional anal- ysis in the Insulin Resistance Atherosclerosis Study (IRAS), that common carotid artery (CCA) IMT was approximately 70 m greater and internal carotid artery (ICA) IMT was 130 m greater in persons with established diabetes relative to those with normal glucose tolerance (NGT), after adjustment for CVD risk factors. 7 Average IMT (CCA and ICA) of persons with undiagnosed diabetes did not differ from the IMT of persons with NGT. To date, only 1 longitudinal analysis has been published that compared the rates of progression of carotid wall IMT in persons with diabetes relative to those without. 8 These investigators have reported a more rapid rate of progression among persons with diabetes. The rate of progression of IMT in undiagnosed diabetes versus diagnosed diabetes (as de- fined by oral tolerance test [OGTT]) is also of interest but has not been reported. Five years of IRAS follow-up data were examined to assess the progression of carotid IMT across these diagnostic categories. Methods The IRAS is a multicenter, observational, epidemiological study of the relations among insulin resistance, CVD, and risk factors in a multiethnic cohort with varying states of glucose tolerance. The design and methods of this study have been described in detail. 9 In brief, the study was conducted at 4 clinical centers. At centers in Oakland and Los Angeles, California, non-Hispanic whites and African Americans were recruited from Kaiser Permanente, a non- profit health maintenance organization. Centers in San Antonio, Tex, and San Luis Valley, Colo, recruited whites and Hispanics from 2 Received February 28, 2003; revision accepted March 28, 2003. From the Department of Public Health Sciences (L.E.W., D.Z., M.A.E.), Wake Forest University School of Medicine, Winston-Salem, NC; the Division of Research (A.J.K.), Kaiser Permanente, Oakland, Calif; the Department of Radiology (D.H.O.’L.), New England Medical Center, Boston, Mass; and Department of Medicine (S.M.H.), University of Texas Health Sciences Center, San Antonio. Correspondence to Lynne E. Wagenknecht, DrPH, Department of Public Health Sciences, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1063. E-mail lwgnkcht@wfubmc.edu © 2003 American Heart Association, Inc. Arterioscler Thromb Vasc Biol. is available at http://www.atvbaha.org DOI: 10.1161/01.ATV.0000072273.67342.6D 1035 Atherosclerosis and Lipoproteins by guest on June 2, 2015 http://atvb.ahajournals.org/ Downloaded from