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Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults

Edstorp, Jessica ; Wei, Yuxia ; Ahlqvist, Emma LU ; Alfredsson, Lars ; Grill, Valdemar ; Groop, Leif LU ; Rasouli, Bahareh ; Sørgjerd, Elin P. ; Thorsby, Per M. and Tuomi, Tiinamaija LU orcid , et al. (2023) In Diabetologia 66. p.70-81
Abstract

Aims/hypotheses: Smoking and use of smokeless tobacco (snus) are associated with an increased risk of type 2 diabetes. We investigated whether smoking and snus use increase the risk of latent autoimmune diabetes in adults (LADA) and elucidated potential interaction with HLA high-risk genotypes. Methods: Analyses were based on Swedish case–control data (collected 2010–2019) with incident cases of LADA (n=593) and type 2 diabetes (n=2038), and 3036 controls, and Norwegian prospective data (collected 1984–2019) with incident cases of LADA (n=245) and type 2 diabetes (n=3726) during 1,696,503 person-years of follow-up. Pooled RRs with 95% CIs were estimated for smoking, and ORs for snus use (case–control data only). The interaction was... (More)

Aims/hypotheses: Smoking and use of smokeless tobacco (snus) are associated with an increased risk of type 2 diabetes. We investigated whether smoking and snus use increase the risk of latent autoimmune diabetes in adults (LADA) and elucidated potential interaction with HLA high-risk genotypes. Methods: Analyses were based on Swedish case–control data (collected 2010–2019) with incident cases of LADA (n=593) and type 2 diabetes (n=2038), and 3036 controls, and Norwegian prospective data (collected 1984–2019) with incident cases of LADA (n=245) and type 2 diabetes (n=3726) during 1,696,503 person-years of follow-up. Pooled RRs with 95% CIs were estimated for smoking, and ORs for snus use (case–control data only). The interaction was assessed by attributable proportion (AP) due to interaction. A two-sample Mendelian randomisation (MR) study on smoking and LADA/type 2 diabetes was conducted based on summary statistics from genome-wide association studies. Results: Smoking (RRpooled 1.30 [95% CI 1.06, 1.59] for current vs never) and snus use (OR 1.97 [95% CI 1.20, 3.24] for ≥15 box-years vs never use) were associated with an increased risk of LADA. Corresponding estimates for type 2 diabetes were 1.38 (95% CI 1.28, 1.49) and 1.92 (95% CI 1.27, 2.90), respectively. There was interaction between smoking and HLA high-risk genotypes (AP 0.27 [95% CI 0.01, 0.53]) in relation to LADA. The positive association between smoking and LADA/type 2 diabetes was confirmed by the MR study. Conclusions/interpretation: Our findings suggest that tobacco use increases the risk of LADA and that smoking acts synergistically with genetic susceptibility in the promotion of LADA. Data availability: Analysis codes are shared through GitHub (https://github.com/jeseds/Smoking-use-of-smokeless-tobacco-HLA-genotypes-and-incidence-of-LADA). Graphical abstract: [Figure not available: see fulltext.]

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publication status
published
subject
keywords
Gene–environment interaction, LADA, Latent autoimmune diabetes in adults, Mendelian randomisation analysis, Smoking, Tobacco use, ANDIS, diabetes
in
Diabetologia
volume
66
pages
70 - 81
publisher
Springer
external identifiers
  • pmid:35900371
  • scopus:85143505472
ISSN
0012-186X
DOI
10.1007/s00125-022-05763-w
language
English
LU publication?
yes
additional info
Funding Information: Open access funding provided by Karolinska Institute. The ESTRID study was funded by grants from the Swedish Research Council (2018-03035), Research Council for Health, Working Life and Welfare (FORTE, 2018-00337), the Novo Nordisk Foundation (NNF19OC0057274) and the Swedish Diabetes Foundation. The post-doctoral fellowship to BR, supported by Novo Nordisk Foundation, has grant no. NNF17OC0027580. YW received a scholarship from the China Scholarship Council (student no. 202006010041). EIRA was funded by the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Rheumatic Foundation, the AFA Insurance Company and Stockholm County Council. ANDIS was financially supported by the Swedish Research Council and the European Research Council Advanced Researcher grant (GA 269045) awarded to LG. Funding Information: We thank the participants in ESTRID, ANDIS and HUNT, as well as administrative personnel, nurses and research team members from all the studies. Preliminary results from this work have been presented as abstracts at the virtual SSSD meeting 2021, the virtual 55th EDEG Annual Meeting 2021, and the virtual 57th EASD Annual Meeting 2021. HUNT is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology NTNU), Trøndelag County Council, Central Norway Regional Health Authority and the Norwegian Institute of Public Health. SC declares shareholding in Swedish Match AB to a value of 5000 euro. These were received as a gift at birth and were originally shares in Volvo Cars Corporation. Through investments and spin offs made by Volvo Cars, part of the shares was transferred into shares in Swedish Match by Volvo in 1996. SC has had no active management of these shares. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution to the data collection was made by SC, BR and JE (ESTRID), LG, EA and TT (ANDIS), LA (EIRA), and EPS, VG, PMT and BOÅ (HUNT). YW was responsible for performing the MR analysis. SC was responsible for conceptualising the research objectives, designed the study and thoroughly revised the manuscript. All authors contributed to the interpretation of the results and critically revised and approved the final version of the manuscript. JE developed the objectives of the study and was responsible for drafting of the manuscript, analysing the observational data and for the integrity of the work as a whole. Publisher Copyright: © 2022, The Author(s).
id
98f5f7e4-c289-4fec-ae63-762b9482c826
date added to LUP
2023-01-26 10:10:36
date last changed
2024-03-21 12:29:28
@article{98f5f7e4-c289-4fec-ae63-762b9482c826,
  abstract     = {{<p>Aims/hypotheses: Smoking and use of smokeless tobacco (snus) are associated with an increased risk of type 2 diabetes. We investigated whether smoking and snus use increase the risk of latent autoimmune diabetes in adults (LADA) and elucidated potential interaction with HLA high-risk genotypes. Methods: Analyses were based on Swedish case–control data (collected 2010–2019) with incident cases of LADA (n=593) and type 2 diabetes (n=2038), and 3036 controls, and Norwegian prospective data (collected 1984–2019) with incident cases of LADA (n=245) and type 2 diabetes (n=3726) during 1,696,503 person-years of follow-up. Pooled RRs with 95% CIs were estimated for smoking, and ORs for snus use (case–control data only). The interaction was assessed by attributable proportion (AP) due to interaction. A two-sample Mendelian randomisation (MR) study on smoking and LADA/type 2 diabetes was conducted based on summary statistics from genome-wide association studies. Results: Smoking (RR<sub>pooled</sub> 1.30 [95% CI 1.06, 1.59] for current vs never) and snus use (OR 1.97 [95% CI 1.20, 3.24] for ≥15 box-years vs never use) were associated with an increased risk of LADA. Corresponding estimates for type 2 diabetes were 1.38 (95% CI 1.28, 1.49) and 1.92 (95% CI 1.27, 2.90), respectively. There was interaction between smoking and HLA high-risk genotypes (AP 0.27 [95% CI 0.01, 0.53]) in relation to LADA. The positive association between smoking and LADA/type 2 diabetes was confirmed by the MR study. Conclusions/interpretation: Our findings suggest that tobacco use increases the risk of LADA and that smoking acts synergistically with genetic susceptibility in the promotion of LADA. Data availability: Analysis codes are shared through GitHub (https://github.com/jeseds/Smoking-use-of-smokeless-tobacco-HLA-genotypes-and-incidence-of-LADA). Graphical abstract: [Figure not available: see fulltext.]</p>}},
  author       = {{Edstorp, Jessica and Wei, Yuxia and Ahlqvist, Emma and Alfredsson, Lars and Grill, Valdemar and Groop, Leif and Rasouli, Bahareh and Sørgjerd, Elin P. and Thorsby, Per M. and Tuomi, Tiinamaija and Åsvold, Bjørn O. and Carlsson, Sofia}},
  issn         = {{0012-186X}},
  keywords     = {{Gene–environment interaction; LADA; Latent autoimmune diabetes in adults; Mendelian randomisation analysis; Smoking; Tobacco use; ANDIS; diabetes}},
  language     = {{eng}},
  pages        = {{70--81}},
  publisher    = {{Springer}},
  series       = {{Diabetologia}},
  title        = {{Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults}},
  url          = {{http://dx.doi.org/10.1007/s00125-022-05763-w}},
  doi          = {{10.1007/s00125-022-05763-w}},
  volume       = {{66}},
  year         = {{2023}},
}