Insulin Resistance, the Metabolic Syndrome, and Risk of Incident Cardiovascular Disease in Nondiabetic American Indians

OBJECTIVE: Insulin resistance (IR) and the metabolic syndrome (MS) are associated with type 2 diabetes and adverse cardiovascular disease (CVD) risk factor profiles. Whether IR and MS predict CVD independently of diabetes and other CVD risk factors is not known. This study examines whether IR and/or presence of MS are independently associated with CVD in nondiabetic American Indians (AI). RESEARCH DESIGN AND METHODS: We examined 2283 nondiabetic AI who were free of CVD at the baseline examination of the Strong Heart Study (SHS). CVD risk factors were measured, IR was quantified using the homeostasis model assessment (HOMA), and MS as defined by the National Cholesterol Education Program Adult Treatment Panel (ATP III) was assessed for each participant. Incident CVD and diabetes were ascertained during follow-up. RESULTS: MS was present in 798 individuals (35%), and 181 participants (7.9%) developed CVD over 7.6 +/- 1.8 years of follow-up. Age, BMI, waist circumference, and triglyceride levels increased and HDL cholesterol decreased across tertiles of HOMA-IR. Risk of diabetes increased as a function of baseline HOMA-IR (6.3, 14.6, and 30.1%; P < 0.001) and MS (12.8 vs. 24.5%). In Cox models adjusted for CVD risk factors, risk of CVD did not increase either as a function of baseline HOMA-IR or MS, but individual CVD risk factors predicted subsequent CVD. CONCLUSIONS: Among nondiabetic AI in the SHS, HOMA-IR and MS both predict diabetes, but neither predicts CVD independently of other established CVD risk factors.