Moderate Alcohol Consumption, Estrogen Replacement Therapy, and Physical Activity Are Associated With Increased Insulin Sensitivity

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Abstract
OBJECTIVE—To investigate 1) associations between environmental factors (alcohol consumption, hormone replacement therapy [HRT], and physical activity) and insulin resistance and secretion, independent of genetic influences; 2) the contribution of abdominal adiposity to these relationships; and 3) whether gene-environment interactions mediate these associations. RESEARCH DESIGN AND METHODS—Reported effects of lifestyle factors on insulin resistance and secretion are inconsistent, possibly due to difficulty in dissecting environmental from genetic influences and to confounding by adiposity. We examined these relationships in 798 nondiabetic female twins. Insulin resistance and secretion were estimated by modified homeostasis model assessment (HOMA-R′ and HOMA-β′, respectively). Percent total body fat and percent central abdominal fat (CAF) were measured by dual-energy X-ray absorptiometry. RESULTS—All categories of alcohol consumption were associated with lower insulin levels and HOMA-β′ than abstinence. Only moderate alcohol consumers (11–20 units/week) had lower HOMA-R′ than abstainers (−0.16 ± 0.09 vs. 0.14 ± 0.13 SD, P = 0.048). This difference was attenuated after controlling for percent CAF (P = 0.57), which was lower in moderate drinkers. Controlling for genetic and smoking effects in cotwin case-control analysis, monozygotic pairs discordant for alcohol consumption had greater within-pair differences in HOMA-R′ than concordant pairs (P = 0.02). Postmenopausal women using estrogen-only HRT had lower HOMA-R′ than non–HRT users (−0.33 ± 0.16 vs. 0.17 ± 0.08 SD, P = 0.003), even after controlling for percent CAF. Lower fasting glucose levels and insulin resistance and secretion indexes in physically active subjects were partly explained by lower abdominal adiposity. CONCLUSIONS—Moderate alcohol consumption, estrogen replacement, and physical activity are associated with increased insulin sensitivity in female twins. The favorable effects of moderate alcohol consumption and physical activity on insulin sensitivity are partly mediated by lower abdominal adiposity.