American Diabetes Association
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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

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posted on 2023-03-03, 16:49 authored by Jessica Edstorp, Emma Ahlqvist, Lars Alfredsson, Dina Mansour Aly, Valdemar Grill, Bahareh Rasouli, Elin P Sørgjerd, Tiinamaija Tuomi, Bjørn O. Åsvold, Sofia Carlsson



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. 


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. 


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. 


AFA Insurance Company

EXODIAB 2009-1039

FORTE 2018-00337

Linneaus 349-2006-237

Novo Nordisk Fonden NNF19OC0057274 NNF17OC0027580

Stockholm County Council

Swedish governmental funding of clinical research (ALF)

Swedish Research Council 2015-2558 2020-02191

Swedish Research Council 2012-5538 2014-6395 2018-03035

The Swedish Diabetes Foundation DIA2022-735

The Swedish Foundation for Strategic Research IRC15–0067


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