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Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults
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. Metho...
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Published in: | Diabetologia 2023-01, Vol.66 (1), p.70-81 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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
pooled
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 |
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ISSN: | 0012-186X 1432-0428 1432-0428 |
DOI: | 10.1007/s00125-022-05763-w |