OBJECTIVE -Long-term exposure to alcohol is associated with an improvement in insulin sensitivity. At this time, however, there is no definitive proof that alcohol per se has an effect on the insulin sensitivity index (S i ) in type 2 diabetes patients. The aim of the present study was to assess the role of acute moderate alcohol intake on insulin sensitivity and insulin secretion in comparable subjects with and without type 2 diabetes.RESEARCH DESIGN AND METHODS -Frequently sampled intravenous glucose tolerance tests (FSIGTs) were performed twice on eight healthy and eight type 2 diabetic volunteers. Forty grams of alcohol (vodka 40% wt/vol) or tap water were sipped from time Ϫ60 min to the end of the FSIGT.RESULTS -Lactate area under the curve (AUC) was higher in both groups during the alcohol study than in the control study. Free fatty acid (FFA) AUC was higher in type 2 diabetic subjects than in control subjects; alcohol slightly reduced FFA by 17% in control subjects (34 Ϯ 4 mmol ⅐ min Ϫ1 ⅐ l Ϫ1 ; P ϭ 0.1) but significantly decreased FFA by 23% in type 2 diabetic subjects (54 Ϯ 10; P ϭ 0.007). ␤-Cell response was markedly reduced in type 2 diabetic subjects regardless of the type of study. Alcohol significantly increased S i in both groups.CONCLUSIONS -Acute alcohol consumption improves insulin action without affecting ␤-cell secretion. This effect may be partly due to the inhibitory effect of alcohol on lipolysis. Alcohol intake increases insulin sensitivity and may partly explain both the J-shaped relationship between the prevalence of diabetes and the amount of alcohol consumption and the decreased mortality for myocardial infarction. Diabetes Care 27:1369 -1374, 2004R eports consistently suggest that the intake of a significant amount of alcohol induces a state of insulin resistance, assessed either with oral or intravenous glucose tolerance tests (1-3). However, a large body of epidemiological evidence from cross-sectional studies also suggests long-term exposure to alcohol is associated with an improvement in insulin sensitivity (4 -8). Furthermore, a substantial number of prospective studies indicate that light to moderate chronic alcohol intake improves glucose metabolism and is protective against coronary artery disease in subjects with type 2 diabetes (9 -13). Historically, alcohol use by the diabetic patient has been controversial; however, in light of these premises, moderate alcohol consumption should, at least in part, contribute to improved insulin sensitivity. Indeed, moderate alcohol intake taken with a meal has been shown to have little or no effect on postprandial glycemic excursions, whereas heavy intake yields opposite effects (14 -20). At this time, however, there is no definitive proof that alcohol per se has an effect on insulin sensitivity in patients with type 2 diabetes. Therefore, the aim of the present study was to test the hypothesis that acute alcohol intake might improve insulin sensitivity and secretion in comparable subjects with and without type 2 diabetes. Moreover, we wi...