Alcohol consumption and its interaction with genetic variants are strongly associated with the risk of type 2 diabetes: a prospective cohort study
Alcohol consumption and its interaction with genetic variants are strongly associated with the risk of type 2 diabetes: a prospective cohort study
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饮酒及其与遗传变异的相互作用与 2 型糖尿病的风险密切相关：一项前瞻性队列研究
DOI：
10.1186/s12986-019-0396-x
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发表时间：
2019
影响因子：
4.5
通讯作者：
Hu Cheng
中科院分区：
文献类型：
--
作者：
Yu Hairong;Wang Tao;Zhang Rong;Yan Jing;Jiang Feng;Li Shanshan;Jia Weiping;Hu Cheng
背景：遗传和生活方式因素都会导致2型糖尿病的发生。饮酒是最普遍的生活习惯之一，但是否以及如何影响2型糖尿病仍存在争议。此外，饮酒是否与遗传风险相互作用还没有定论。因此，我们旨在探讨酒精、遗传风险及其潜在交互作用对2型糖尿病风险的影响。方法上海糖尿病研究(SHDS)共有2546名参与者，611例合并2型糖尿病和糖调节受损(IGR)的病例。我们构建了2型糖尿病的加权遗传风险评分(GRS)，并将GRS分为三个层次。计算β细胞功能(HOMA-B)和胰岛素抵抗(HOMA-IR)的稳态模型评估。然后分别用Logistic回归模型和多元线性回归模型检验基线饮酒和遗传风险对血糖恶化、胰岛素抵抗(IR)和胰岛β细胞功能(BC)的影响。此外，我们还研究了饮酒与以下因素的交互作用：(1)2型糖尿病、IR、BC、体重指数(BMI)和腰臀比(WHR)的GRS；(2)用于建立上述GRS的每一个单核苷酸多态性(SNPs)。结果饮酒和较高的T2D-GRS均导致血糖恶化的发生率较高[优势比(OR)，2.24，95%可信区间(CI)，1.76~2.87；OR，1.25，95%CI，1.11~1.42；OR，1.25，95%CI，1.11~1.42]。酒精降低胰岛素敏感性，并通过增强β细胞功能来补偿(β = 1.98，P<； .0001和β = − 1.97，P <； .0001分别用于HOMA-IR和反向HOMA-β)。T2D-GRS使胰岛素分泌恶化(β = 为0.10，对于反向HOMA-B，P= 0.0069)，但不影响胰岛素敏感性(P= 0.0856)。此外，酒精和T2D-GRS之间存在显著的交互作用(P交互作用= 0.0318)，这表明在T2D-GRS较低的组中，酒精与2型糖尿病的关联比T2D-GRS较高的组强得多。而且这种交互作用在男性中更为明显(P交互作用= 0.0176)，而在女性中(P交互作用= 0.3285)。没有单一的SNP与酒精摄入量有强烈的相互作用。结论/解释饮酒会增加IR，特别是在T2D-GRS低的男性，从而显著增加2型糖尿病的风险，强调了在建议健康的生活方式习惯以预防糖尿病时避免饮酒的重要性。
BackgroundBoth 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.MethodsThe 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.ResultsAlcohol 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 (Pinteraction= 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 (Pinteraction= 0.0176) than in women (Pinteraction= 0.3285). No single SNP interacted strongly with alcohol intake.Conclusions/interpretationAlcohol 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.