The Relationship Between Dysglycemia and Atherosclerosis in South Asian, Chinese, and European Individuals in Canada A randomly sampled cross-sectional study HERTZEL C. GERSTEIN, MD, MSC 1 SONIA ANAND, MD, MSC 1 QI LONG YI, MSC 1,2 VLADIMIR VUKSAN, PHD 3 EVA LONN, MD, MSC 1 KOON TEO, MBBCH 1 KLAS MALMBERG, MD, PHD 4 MATTHEW MCQUEEN, MBCHB 1 SALIM YUSUF, MD, MBBS, DPHIL 1 FOR THE SHARE INVESTIGATORS* OBJECTIVE — Raised glucose levels extending from normal into the diabetic range (dysgly- cemia) are an emerging risk factor for clinical cardiovascular events. The relationship between dysglycemia and atherosclerosis (AS) in the general population and in different ethnic groups remains controversial. RESEARCH DESIGN AND METHODS — Glucose tolerance, HbA 1c , other metabolic risk factors for AS, and carotid mean maximal intimal media thickness were assessed in a random sample of 979 Canadians of South Asian, Chinese, and European descent. RESULTS — The age and sex-adjusted intimal medial thickness increased 0.026 mm for every 0.9% increase in HbA 1c in all participants (P  0.0001) and in those of South Asian (P = 0.018), Chinese (P = 0.002), and European (P  0.0001) descent. This progressive curvilinear rela- tionship was most apparent at HbA 1c levels 5.7%. The HbA 1c -AS relationship persisted after adjustment for ethnicity, age, sex, diabetes status, abdominal obesity, insulin resistance, insulin secretion, fasting free fatty acids, blood pressure, and/or dyslipidemia (P  0.004). Both diabetes (P = 0.002) and HbA 1c (P  0.0001) were determinants of the intimal medial thickness when included in separate statistical models. When included together in a single model, HbA 1c (P  0.0001) but not diabetes (P = 0.6) was a significant determinant. CONCLUSIONS — The degree of AS is related to the level of HbA 1c irrespective of diabetes status and independent of abdominal obesity and other markers of the metabolic syndrome. This progressive relationship between HbA 1c and AS was observed within different ethnic groups. Diabetes Care 26:144 –149, 2003 P eople with diabetes are at high risk for cardiovascular (CV) disease (1). This risk varies with glucose levels as well as HbA 1c levels. This graded rela- tionship between plasma glucose and CV risk is observed in people with diabetes (2– 4) and in nondiabetic individuals with high glucose levels that are below the di- abetes cutoffs (5–10). These data suggest that glucose may promote atherosclerosis (AS) either di- rectly or indirectly. Alternatively, it may be a marker for metabolic abnormalities that may themselves promote AS. To date, few studies have explored this link be- tween dysglycemia (i.e., any elevated glu- cose level) and AS using standardized methods. In addition, this relationship has not been explored within different ethnic groups. The Study of Health Assessment and Risk in Ethnic Groups (SHARE) measured diabetes prevalence, glucose intolerance, HbA 1c , other CV risk factors, and carotid AS (by B-mode carotid ultrasound) in a large population-based sample of Canadi- ans of South Asian, Chinese, and Euro- pean origin (11). This article reports on the importance of dysglycemia as an AS risk factor and explores the relationship between ethnicity, metabolic CV risk fac- tors, and AS in this population. RESEARCH DESIGN AND METHODS Study population SHARE was a population-based study of carotid AS and its determinants in 985 individuals of South Asian, Chinese, and European origin living in Canada for 5 years. Detailed descriptions of the proto- col, sampling frames, and major results have been published (11,12). Briefly, a database of South Asian and Chinese sur- names in the telephone directories of Hamilton, Toronto, and Edmonton, Can- ada, was randomly sampled. Selected households were mailed an introductory letter and then contacted by phone. Eligi- ble individuals of the appropriate ethnic- ity (defined by their ancestral origins) aged 35–75 years who had lived in Can- ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From 1 McMaster University and the Population Health Research Institute, Hamilton, Ontario, Canada; 2 Princess Margaret Hospital and the University of Toronto, Toronto, Ontario, Canada; the 3 Risk Factor Modification Center, St. Michael’s Hospital and the University of Toronto, Toronto, Ontario, Canada; and the 4 Department of Cardiology, Karolinska Institute, Stockholm, Sweden. Address correspondence and reprint requests to Dr. H.C. Gerstein, Department of Medicine, Room 3V38, 1200 Main St. West, Hamilton, Ontario, L8N 3Z5, Canada. E-mail: gerstein@mcmaster.ca. Received for publication 12 June 2002 and accepted in revised form 7 October 2002. *A list of the SHARE investigators can be found in reference 11. Abbreviations: AS, atherosclerosis; CV, cardiovascular; HOMA, homeostasis model assessment; HOMA-, HOMA for -cell secretion; HOMA-IR, HOMA for insulin resistance; IMT, intimal media thick- ness; MMIMT, maximum IMT; SHARE, Study of Health Assessment and Risk in Ethnic Groups. A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. Pathophysiology/Complications O R I G I N A L A R T I C L E 144 DIABETES CARE, VOLUME 26, NUMBER 1, JANUARY 2003 Downloaded from http://diabetesjournals.org/care/article-pdf/26/1/144/648185/dc0103000144.pdf by guest on 25 January 2023