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

Jessica Edstorp, Emma Ahlqvist, Lars Alfredsson, Dina Mansour Aly, Valdemar Grill, Bahareh Rasouli, Elin P. Sørgjerd, Tiinamaija Tuomi, Bjørn O. Åsvold, Sofia Carlsson

Research output: Contribution to journalArticlepeer-review

Abstract

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 T2D, insulin resistance (IR), and insulin secretion (IS) aggravate these associations. RESEARCH DESIGN AND METHODS 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. 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 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. CONCLUSIONS 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.

Original languageEnglish
Pages (from-to)1028-1036
Number of pages9
JournalDiabetes Care
Volume46
Issue number5
DOIs
Publication statusPublished - 2023 May

Subject classification (UKÄ)

  • Endocrinology and Diabetes

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