OBJECTIVE Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. This reduced risk might be explained by improved insulin sensitivity or improved glycemic status, but results of intervention studies on this relation are inconsistent. The purpose of this study was to conduct a systematic review and meta-analysis of intervention studies investigating the effect of alcohol consumption on insulin sensitivity and glycemic status. RESEARCH DESIGN AND METHODS PubMed and Embase were searched up to August 2014. Intervention studies on the effect of alcohol consumption on biological markers of insulin sensitivity or glycemic status of at least 2 weeks' duration were included. Investigators extracted data on study characteristics, outcome measures, and methodological quality. RESULTS Fourteen intervention studies were included in a meta-analysis of six glycemic end points. Alcohol consumption did not influence estimated insulin sensitivity (standardized mean difference [SMD] 0.08 [−0.09 to 0.24]) or fasting glucose (SMD 0.07 [−0.11 to 0.24]) but reduced HbA1c (SMD −0.62 [−1.01 to −0.23]) and fasting insulin concentrations (SMD −0.19 [−0.35 to −0.02]) compared with the control condition. Alcohol consumption among women reduced fasting insulin (SMD −0.23 [−0.41 to −0.04]) and tended to improve insulin sensitivity (SMD 0.16 [−0.04 to 0.37]) but not among men. Results were similar after excluding studies with high alcohol dosages (>40 g/day) and were not influenced by dosage and duration of the intervention. CONCLUSIONS Although the studies had small sample sizes and were of short duration, the current evidence suggests that moderate alcohol consumption may decrease fasting insulin and HbA1c concentrations among nondiabetic subjects. Alcohol consumption might improve insulin sensitivity among women but did not do so overall.

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The causal effects of alcohol-in-moderation on cardiometabolic health are continuously debated. Mendelian randomization (MR) is an established method to address causal questions in observational studies. We performed a systematic review of the current evidence from MR studies on the association between alcohol consumption and cardiometabolic diseases, all-cause mortality and cardiovascular risk factors. We performed a systematic search of the literature, including search terms on type of design and exposure. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. We additionally looked at exploration of non-linearity. We reported the direction of the studied associations. Our search yielded 24 studies that were eligible for inclusion. A full instrumental variable analysis was performed in 17 studies (71%) and 13 out of 24 studies (54%) validated all three key assumptions. Five studies (21%) assessed potential non-linearity. In general, null associations were reported for genetically predicted alcohol consumption with the primary outcomes cardiovascular disease (67%) and diabetes (75%), while the only study on all-cause mortality reported a detrimental association. Considering the heterogeneity in methodological quality of the included MR studies, it is not yet possible to draw conclusions on the causal role of moderate alcohol consumption on cardiometabolic health. As MR is a rapidly evolving field, we expect that future MR studies, especially with recent developments regarding instrument selection and non-linearity methodology, will further substantiate this discussion.