Incidence of LADA and type 2 diabetes in relation to tobacco use and genetic susceptibility to type 2 diabetes and related traits: findings from a Swedish case-control study and the Norwegian HUNT Study

Objective 

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 type 2 diabetes, insulin resistance (IR) and insulin secretion (IS) aggravate these associations.

Research design and methods

We used data from two population-based Scandinavian studies with incident cases of LADA (n=839) and type 2 diabetes (n=5771), matched controls (n=3068) 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 odds ratios (OR) for snus or tobacco/GRS (case-control data). We estimated additive (proportion attributable to interaction [AP]) and multiplicative interaction between tobacco use and GRSs. 

Results

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 to 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 type 2 diabetes. 

Conclusion

Tobacco use may confer a higher risk of LADA in individuals with genetic susceptibility to type 2 diabetes and insulin resistance, whereas genetic susceptibility does not seem to influence the increased type 2 diabetes incidence associated with tobacco use.