Smoking Is Associated With Reduced Risk of Autoimmune Diabetes in Adults Contrasting With Increased Risk in Overweight Men With Type 2 Diabetes: A 22-year follow-up of the HUNT study

OBJECTIVE: To investigate the association between smoking habits and risk of autoimmune diabetes in adults and of type 2 diabetes. RESEARCH DESIGN AND METHODS: We used data from the three surveys of the Nord-Trøndelag Health Study, spanning 1984–2008 and including a cohort of 90,819 Norwegian men (48%) and women (52%) aged ≥20 years. Incident cases of diabetes were identified by questionnaire and classified as type 2 diabetes (n = 1,860) and autoimmune diabetes (n = 140) based on antibodies to glutamic decarboxylase (GADA) and age at onset of diabetes. Hazard ratios (HRs) adjusted for confounders were estimated by Cox proportional hazards regression models. RESULTS: The risk of autoimmune diabetes was reduced by 48% (HR 0.52 [95% CI 0.30–0.89]) in current smokers and 58% in heavy smokers (0.42 [0.18–0.98]). The reduced risk was positively associated with number of pack-years. Heavy smoking was associated with lower levels of GADA (P = 0.001) and higher levels of C-peptide (964 vs. 886 pmol/L; P = 0.03). In contrast, smoking was associated with an increased risk of type 2 diabetes, restricted to overweight men (1.33 [1.10–1.61]). Attributable proportion due to an interaction between overweight and heavy smoking was estimated to 0.40 (95% CI 0.23–0.57). CONCLUSIONS: In this epidemiological study, smoking is associated with a reduced risk of autoimmune diabetes, possibly linked to an inhibitory effect on the autoimmune process. An increased risk of type 2 diabetes was restricted to overweight men.