Alcohol Intake and Serum Glucose Levels from the Perspective of a Mendelian Randomization Design: The KCPS-II Biobank

BACKGROUND Previous studies have suggested that alcohol intake is associated with increased fasting serum glucose (FSG), but the nature of the relationship remains unknown. We used Mendelian randomization analysis to assess the causal effect of alcohol intake on FSG in a middle-aged Korean population. METHODS Clinical data including FSG and alcohol intake were collected from 156,386 Koreans aged 20 years or older who took part in the Korean Cancer Prevention Study-II (KCPS-II) Biobank Cohort. The single nucleotide polymorphism rs671 in ALDH2 was genotyped among 2,993 men and 1,374 women in 2016. This was a randomly selected subcohort of KCPS-II Biobank participants. RESULTS Alcohol consumption was positively associated with FSG level in men, but not in women. The rs671 major G allele was associated with increased alcohol intake (F-statistic = 302.62) and an increase in FSG in men. Using Mendelian randomization analysis, alcohol intake increased FSG by 1.78 mg/dL per alcohol unit (10 g ethanol) per day (95% CI: 0.97-2.59) in men. The associations became stronger when we excluded heavy drinkers and the elderly. However, in women, no significant association between rs671 and alcohol or serum glucose was found. CONCLUSION Using Mendelian randomization analysis, we suggest a causal relationship between alcohol intake and FSG among Korean men. Moreover, we found that the ALDH2 variant rs671 was not associated with FSG among Korean women.