HOMA insulin sensitivity index and the risk of all-cause mortality and cardiovascular disease events in the general population: the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) study

We assessed whether the relationships between insulin sensitivity and all-cause mortality as well as fatal or non-fatal cardiovascular disease (CVD) events are independent of elevated blood glucose, high blood pressure, dyslipidaemia and body composition in individuals without diagnosed diabetes. Between 1999 and 2000, baseline fasting insulin, glucose and lipids, 2 h plasma glucose, HbA(1c), anthropometrics, blood pressure, medication use, smoking and history of CVD were collected from 8,533 adults aged > 35 years from the population-based Australian Diabetes, Obesity and Lifestyle study. Insulin sensitivity was estimated by HOMA of insulin sensitivity (HOMA-%S). Deaths and fatal or non-fatal CVD events were ascertained through linkage to the National Death Index and medical records adjudication. After a median of 5.0 years there were 277 deaths and 225 CVD events. HOMA-%S was not associated with all-cause mortality. Compared with the most insulin-sensitive quintile, the combined fatal or non-fatal CVD HR (95% CI) for quintiles of decreasing HOMA-%S were 1.1 (0.6-1.9), 1.4 (0.9-2.3), 1.6 (1.0-2.5) and 2.0 (1.3-3.1), adjusting for age and sex. Smoking, CVD history, hypertension, lipid-lowering medication, total cholesterol and waist-to-hip ratio moderately attenuated this relationship. However, the association was rendered non-significant by adding HDL. Fasting plasma glucose, but not HOMA-%S significantly improved the prediction of CVD, beyond that seen with other risk factors. In this cohort, HOMA-%S showed no association with all-cause mortality and only a modest association with CVD events, largely explained by its association with HDL. Fasting plasma glucose was a better predictor of CVD than HOMA-%S.