Abstract
AIMS/INTRODUCTION: The sex-specific association between alcohol consumption and glycemic level and whether the association differs by genetic susceptibility to alcohol is unclear. The present study aimed to examine the association of alcohol consumption and genetic variants in alcohol-metabolizing enzymes with glycemic level, as well as their sex differences, in East Asian individuals with type 2 diabetes. MATERIALS AND METHODS: In total, 4,923 Japanese individuals with type 2 diabetes were included. Participants were classified based on alcohol drinking status, alcohol consumption amount (<20, 20-39, or ≥40 g/day), and ADH1B (rs1229984) and ALDH2 (rs671) genotype, and the associations with HbA(1c) levels were examined cross-sectionally. RESULTS: In men, compared with never drinkers, an increase in the alcohol consumption amount was associated with a decrease in HbA(1c) levels (P for trend <0.001). By contrast, in women, a mild-to-moderate consumption amount (<20 g/day) was associated with decreased HbA(1c) levels, whereas ≥20 g/day consumption was associated with increased HbA(1c) levels, indicating a J-shaped relationship. Regarding the association with genetic variants in alcohol-metabolizing enzymes, HbA(1c) increased linearly with an increasing number of A alleles in ALDH2 (P for trend <0.001). However, the HbA(1c) level did not show a significant trend across the ADH1B genotype. The association between alcohol consumption and HbA(1c) levels was not modified by genetic variants in ADH1B or ALDH2. CONCLUSIONS: These findings highlight the importance of a sex-specific approach to alcohol drinking habits in managing glycemic control for individuals with type 2 diabetes, irrespective of genetic predisposition to alcohol metabolism.