1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
2Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Lund University, Malmö, Sweden.
Diabetes Care. 2023 May 1;46(5):1028-1036. doi: 10.2337/dc22-2284.
Smoking and Swedish smokeless tobacco (snus) are associated with latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2D). Our aim was to investigate whether genetic susceptibility to T2D, insulin resistance (IR), and insulin secretion (IS) aggravate these associations.
We used data from two population-based Scandinavian studies with case subjects with LADA (n = 839) and T2D (n = 5,771), matched control subjects (n = 3,068), and 1,696,503 person-years at risk. Pooled, multivariate relative risks (RR) with 95% CI were estimated for smoking/genetic risk scores (T2D-GRS, IS-GRS, and IR-GRS), and ORs for snus or tobacco/GRS (case-control data). We estimated additive (proportion attributable to interaction [AP]) and multiplicative interaction between tobacco use and GRS.
The RR of LADA was elevated in high IR-GRS heavy smokers (≥15 pack-years; RR 2.01 [CI 1.30, 3.10]) and tobacco users (≥15 box/pack-years; RR 2.59 [CI 1.54, 4.35]) compared with low IR-GRS individuals without heavy use, with evidence of additive (AP 0.67 [CI 0.46, 0.89]; AP 0.52 [CI 0.21, 0.83]) and multiplicative (P = 0.003; P = 0.034) interaction. In heavy users, there was additive interaction between T2D-GRS and smoking, snus, and total tobacco use. The excess risk conferred by tobacco use did not differ across GRS categories in T2D.
Tobacco use may confer a higher risk of LADA in individuals with genetic susceptibility to T2D and insulin resistance, whereas genetic susceptibility does not seem to influence the increased T2D incidence associated with tobacco use.
吸烟和瑞典无烟烟草（鼻烟）与成人隐匿性自身免疫性糖尿病（LADA）和 2 型糖尿病（T2D）有关。我们旨在研究 2 型糖尿病、胰岛素抵抗（IR）和胰岛素分泌（IS）的遗传易感性是否会加剧这些关联。
我们使用了两项基于人群的斯堪的纳维亚研究的数据，病例组为 LADA（n=839）和 T2D（n=5771）患者，匹配对照组（n=3068），风险人群为 1696503 人年。采用多变量相对风险（RR）和 95%CI 对吸烟/遗传风险评分（T2D-GRS、IS-GRS 和 IR-GRS）进行了汇总估计，并对鼻烟或烟草/GRS（病例对照数据）进行了比值比（OR）估计。我们还估计了烟草使用与 GRS 之间的相加（交互归因比例 [AP]）和相乘交互作用。
高 IR-GRS 重度吸烟者（≥15 包年；RR 2.01 [CI 1.30，3.10]）和烟草使用者（≥15 盒/包年；RR 2.59 [CI 1.54，4.35]）发生 LADA 的风险高于低 IR-GRS 非重度使用者，且存在相加（AP 0.67 [CI 0.46，0.89]；AP 0.52 [CI 0.21，0.83]）和相乘（P=0.003；P=0.034）交互作用的证据。在重度使用者中，T2D-GRS 与吸烟、鼻烟和总烟草使用之间存在相加交互作用。在 T2D 中，烟草使用所带来的额外风险在 GRS 类别之间没有差异。
在有 2 型糖尿病和胰岛素抵抗遗传易感性的个体中，吸烟可能会带来更高的 LADA 风险，而遗传易感性似乎不会影响与吸烟相关的 T2D 发生率增加。
