BACKGROUND AND AIM:The development of insulin resistance is a critical step in the pathogenesis of type 2 diabetes. The effect of alcohol intake on insulin sensitivity/resistance is not well defined. The aim of this study was to examine the association between alcohol intake and insulin resistance in a sample of middle-aged men and women with data on a wide range of potential confounding factors, including diet. METHODS:We performed a cross sectional study involving a group of 1018 men and women, sampled from 17 general practice lists in the South of Ireland, with a response rate of 69%. Participants completed a detailed health and lifestyle questionnaire and a food frequency questionnaire and provided fasting blood samples for analysis of glucose and insulin. Insulin resistance was estimated on the basis of fasting glucose and insulin, using the glucose homeostasis model (HOMA scores). Insulin resistance was defined as the upper quartile of the HOMA scores. RESULTS:We found evidence of a U-shaped relationship between alcohol intake and insulin resistance fitted as a continuous variable (HOMA scores) with lowest levels in light drinkers (between 0.5 to 0.99 units per day) relative to the other drinking categories. However no significant association between alcohol intake and HOMA score was observed in fully adjusted analyses, including adjustment for dietary saturated fat and fruit and vegetables intake. In logistic regression analysis with insulin resistance (categorical) as the dependent variable, we observed that ex-drinkers were at higher risk of insulin resistance compared to occasional drinkers independently of age, sex, BMI and waist circumference, (OR=2.4, 95% CI, 1.1-5.7, p=0.04). On further adjustment for potential confounders including diet this association was also attenuated and was non-significant. CONCLUSIONS:The reported effects of alcohol intake on insulin resistance may be confounded by other aspects of lifestyle, especially diet.