Alcohol consumption, alcohol‐metabolizing enzyme genotypes, and glycemic control in type 2 diabetes: Sex‐specific findings from the Fukuoka Diabetes Registry

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.