Alcohol consumption and its interaction with genetic variants are strongly associated with the risk of type 2 diabetes: a prospective cohort study

BACKGROUND: Both genetic and lifestyle factors contribute to the incidence of type 2 diabetes. It yet remains controversial whether and how alcohol consumption, one of the most prevalent lifestyle habits, influences type 2 diabetes. Moreover, whether alcohol consumption interacts with genetic risk is inconclusive. Thus, we aimed to explore the effects of alcohol, genetic risk and their potential interactions on type 2 diabetes risk. METHODS: The Shanghai Diabetes study (SHDS) had a total of 2546 participants with 611 incident cases of combined type 2 diabetes and impaired glucose regulation (IGR). We constructed weighted genetic risk score (GRS) for type 2 diabetes and categorized the GRS into three strata. And the homeostatic model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated. Then we used logistic regression models and multiple linear regression models to examine the influence of both baseline alcohol consumption and genetic risk on blood glucose deterioration, insulin resistance (IR) and beta cell function (BC), respectively. Moreover, we investigated the interactions of alcohol intake with: (1) GRSs for type 2 diabetes, IR, BC, body mass index (BMI) and waist-to-hip ratio (WHR); and (2) each of the single nucleotide polymorphisms (SNPs) used to establish the GRSs mentioned above. RESULTS: Alcohol consumption and higher T2D-GRS both contributed to a higher incidence rate of blood glucose deterioration [odds ratio (OR), 2.24, 95% confidence interval (CI), 1.76–2.87; OR, 1.25, 95% CI, 1.11–1.42; respectively]. Alcohol reduced insulin sensitivity and compensated by enhancing beta cell function (β = 1.98, P < .0001 and β = − 1.97, P < .0001 for HOMA-IR and inverse HOMA-β, respectively). T2D-GRS deteriorated insulin secretion (β = 0.10, P = 0.0069 for inverse HOMA-B) but not insulin sensitivity (P = 0.0856). Moreover, there was a significant interaction between alcohol and T2D-GRS (P(interaction) = 0.0318), suggesting the association between alcohol and type 2 diabetes was much stronger in the lower T2D-GRS group than in the higher T2D-GRS group. And this interaction was more pronounced in men (P(interaction) = 0.0176) than in women (P(interaction) = 0.3285). No single SNP interacted strongly with alcohol intake. CONCLUSIONS/INTERPRETATION: Alcohol consumption strongly increased the risk of type 2 diabetes by increasing IR, especially in men with low T2D-GRS, highlighting the importance of refraining from drinking alcohol when making recommendations for healthy lifestyle habits to prevent diabetes.