We measured cardiovascular disease (CVD) risk factors and their relationship to glucose intolerance in a Native Canadian population with very high rates of Type 2 diabetes mellitus. Five hundred and twenty five study-eligible Ojibwa-Cree individuals age 18 and over in the community of Sandy Lake, Canada who had participated in a population-based survey were studied. Diabetes status, plasma concentrations of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), calculated low density lipoprotein-cholesterol (LDL-C), waist/hip ratio (WHR), BMI, systolic and diastolic BP, and history of smoking were compared to a standard national population. Extremely high rates of obesity (BMI and WHR) were identified in the study population and were associated with increasing glucose intolerance for both males and females. Rates of smoking exceeded 70 and 80% in females and males, respectively. Interestingly, despite obesity individuals who had normal glucose tolerance had significantly lower rates of high risk TC, TG, LDL-C, and HDL-C levels compared to a national Canadian population survey. However, with worsening glucose intolerance, TC, TG, LDL-C and HDL-C dramatically deteriorated in comparison to nationally published levels. These changes in cardiovascular risk factors, as a consequence of diabetes, appear to result in increased clinical outcomes. Admission to hospital for Ischemic Heart Disease (IHD) for Sandy Lake residents increased from a rate of 34.8/10,000 to 109.1/10,000 in 15 years. Although this and similar populations have historically reported low rates of CVD, the impact of diabetes on lipid risk factor is having devastating consequences on cardiovascular outcomes. This trend is expected to continue unless the high rates of diabetes can be modified.