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

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Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults
Diabetologia ( IF 8.4 ) Pub Date : 2022-07-28 , DOI: 10.1007/s00125-022-05763-w
Jessica Edstorp ₁ , Yuxia Wei ₁ , Emma Ahlqvist ₂ , Lars Alfredsson _{1,

3} , Valdemar Grill ₄ , Leif Groop _{2,

5} , Bahareh Rasouli _{1,

6} , Elin P Sørgjerd _{7,

8} , Per M Thorsby _{9,

10} , Tiinamaija Tuomi _{2,

5,

11,

12,

13} , Bjørn O Åsvold _{7,

8,

14} , Sofia Carlsson ₁

Affiliation

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Sciences in Malmö, Clinical Research Centre, Lund University, Malmö, Sweden.
Center for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden.
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland.
Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA.
HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Endocrinology, Clinic of Medicine, St Olavs Hospital, Trondheim, Norway.
Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Aker, Oslo, Norway.
Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway.
Division of Endocrinology, Abdominal Center, Helsinki University Hospital, Helsinki, Finland.
Research Program for Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
Folkhälsan Research Center, Helsinki, Finland.
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

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

中文翻译：

成人吸烟、使用无烟烟草、HLA 基因型和潜在自身免疫性糖尿病的发病率

目标/假设

吸烟和使用无烟烟草（鼻烟）会增加患 2 型糖尿病的风险。我们调查了吸烟和使用鼻烟是否会增加成人潜在自身免疫性糖尿病 (LADA) 的风险，并阐明了与 HLA 高危基因型的潜在相互作用。

方法

分析基于瑞典病例对照数据（2010-2019 年收集），其中包括 LADA（ n = 593）和 2 型糖尿病（ n = 2038）事件病例以及 3036 名对照，以及挪威前瞻性数据（1984-2019 年收集），在 1,696,503 人年的随访期间，LADA ( n = 245) 和 2 型糖尿病 ( n = 3726) 的事件病例。估计吸烟的汇总 RR（95% CI），以及鼻烟使用的 OR（仅病例对照数据）。交互作用通过交互作用的归因比例（AP）来评估。根据全基因组关联研究的汇总统计数据，进行了一项关于吸烟和 LADA/2 型糖尿病的两样本孟德尔随机化 (MR) 研究。

结果

吸烟（当前与从未使用相比，RR_为1.30 [95% CI 1.06, 1.59]）和鼻烟使用（≥15盒年与从未使用相比，OR 1.97 [95% CI 1.20, 3.24]）与 LADA 风险增加相关。 2 型糖尿病的相应估计值分别为 1.38 (95% CI 1.28, 1.49) 和 1.92 (95% CI 1.27, 2.90)。吸烟和 HLA 高危基因型（AP 0.27 [95% CI 0.01, 0.53]）与 LADA 之间存在相互作用。 MR 研究证实了吸烟与 LADA/2 型糖尿病之间的正相关性。