Elevated Carotid Artery Intima-Media Thickness Levels in Individuals Who Subsequently Develop Type 2 Diabetes Kelly J. Hunt, Ken Williams, David Rivera, Daniel H. O’Leary, Steve M. Haffner, Michael P. Stern, Clicerio Gonza ´lez Villalpando Objective—We examined whether B-mode ultrasound– detected carotid artery intima-media thickness (IMT) was elevated before the onset of clinical diabetes. Methods and Results—The study population for these analyses included 1127 nondiabetic participants, 66 prediabetic participants, and 303 diabetic participants with a mean age of 49.8 years who participated in the Mexico City Diabetes Study, a prospective cohort study. Common carotid artery (CCA) and internal carotid artery (ICA) IMTs were measured bilaterally by B-mode ultrasound. Age- and sex-adjusted mean ICA and CCA IMTs were both significantly higher among prediabetic individuals {0.81 mm [95% confidence interval (CI), 0.75– 0.88] and 0.72 mm [95% CI, 0.69 – 0.75], respectively} than in individuals who remained free of diabetes [0.71 mm (95% CI, 0.69 – 0.72) and 0.69 mm (95% CI, 0.68 – 0.69), respectively]. However, after adjustment for established cardiovascular risk factors, ICA IMT, but not CCA IMT, remained significantly higher among prediabetic individuals [0.81 mm (95% CI, 0.75– 0.88) and 0.71 mm (95% CI, 0.68 – 0.74)] than in individuals who remained free of diabetes [0.71 mm (95% CI, 0.69 – 0.72) and 0.69 mm (95% CI, 0.68 – 0.70)]. Conclusions—The present study provides direct evidence at the vascular level that atherosclerosis levels are elevated before the clinical onset of diabetes. (Arterioscler Thromb Vasc Biol. 2003;23:1845-1850.) Key Words: atherosclerosis  carotid arteries  imaging  diabetes mellitus A lthough previous studies have established that coronary heart disease (CHD) risk factors are elevated before the clinical onset of diabetes 1–5 and a recent study has reported increased cardiovascular disease risk before the clinical onset of diabetes, 6 direct evidence of increased atherosclerosis before a clinical diagnosis of diabetes has not been docu- mented. Documenting not only increased cardiovascular risk factors but increased atherosclerosis as well provides direct evidence that the atherosclerotic process is accelerated before the onset of clinical diabetes. Moreover, although type 2 diabetes is commonly considered a risk factor for CHD, treatment and control of hyperglycemia in type 2 diabetes have, at best, only a modest effect on reducing the risk of CHD associated with diabetes. 7 If the atherosclerotic process is accelerated before the onset of clinical diabetes, then preventing diabetes itself, either by altering lifestyle or pharmacologically, might be the optimum way to reduce the CHD risk associated with diabetes. See page 1715 Recently, the Diabetes Prevention Program was one of several clinical trials to indicate that either through diet and exercise or with the aid of a pharmacologic agent it is possible to lower the incidence of diabetes among individuals at high risk for the disease. 8 –10 In short, there are lifestyle and pharmacologic interventions available that prevent diabetes. Hence, evidence suggesting that prediabetic individuals have not only elevated CHD risk factors but also elevated levels of subclinical atherosclerosis would indicate the importance of a lifestyle or pharmacologic intervention before the onset of clinical diabetes. Therefore, we examined (1) whether B-mode ultrasound– detected carotid artery intima-media thickness (IMT) was elevated in prediabetic individuals when compared with individuals who remained free of diabetes and (2) whether increased carotid artery IMT predicted incident diabetes. Methods The Mexico City Diabetes Study The Mexico City Diabetes Study is a population-based cohort of 2282 men and women first examined between 1990 and 1992 who were invited to return for 2 follow-up exams, the first conducted between 1993 and 1995 and the second from 1997 to 1999. 11 Participants were randomly selected from 6 low-income “colonias” Received July 30, 2003; revision accepted August 20, 2003. From the Division of Clinical Epidemiology (K.J.H., K.W., S.M.H., M.P.S.), Department of Medicine, University of Texas Health Science Center at San Antonio; Centro de Estudios en Diabetes (D.R., C.G.V.), The American-British Cowdray Medical Center, Mexico City, Mexico; the Department of Radiology (D.H.O’L.), Tufts–New England Medical Center, Boston, Mass; and Unidades de Investigación Médica en Enfermedades Metabólicas y Epidemiología Clínica (C.G.V.), Hospital Gabriel Mancera, Instituto Mexicano del Seguro Social, Mexico City, Mexico. Correspondence to Kelly J. Hunt, PhD, Division of Clinical Epidemiology, UTHSCSA, 7703 Floyd Curl Dr, San Antonio, TX 78229[hyphen]3900. E-mail huntk@uthscsa.edu © 2003 American Heart Association, Inc. Arterioscler Thromb Vasc Biol. is available at http://www.atvbaha.org DOI: 10.1161/01.ATV.0000093471.58663.ED 1845 Atherosclerosis and Lipoproteins by guest on March 14, 2016 http://atvb.ahajournals.org/ Downloaded from