Alcohol, tobacco and the risk of LADA-latent autoimmune diabetes in adults

Diabetes is a common and increasing public health problem. Knowledge of risk factors is a prerequisite for efficient prevention; such knowledge is extensive for type 2 diabetes but limited for autoimmune forms of diabetes. LADA-latent autoimmune diabetes in adults is an autoimmune form of diabetes that develops in adults and has features of both type 1 and type 2 diabetes. It accounts for relatively large proportion of all diabetes patients, yet risk factors are largely unexplored. The aim of this thesis was to investigate the influence of tobacco exposure and alcohol consumption on the risk of LADA, and also to explore these factors in relation to type 2 diabetes, to compare the etiology of these adult onset forms of diabetes.

Analyses were based on data from two large Scandinavian population-based studies; the Norwegian HUNT-study, a prospective cohort study conducted between 1984 and 2008, and ESTRID, an ongoing Swedish case-control study with incident cases. Information on lifestyle including alcohol consumption and tobacco use was collected by questionnaire. Cases of diabetes were identified by self-report (HUNT) or through the health care system (ESTRID). Patients with LADA had onset ≥35 years and were glutamic acid decarboxylase autoantibody (GADA) positive. Information on lack of insulin treatment (HUNT) or C-peptide levels (ESTRID) were used to indicate a slow onset.

Alcohol consumption was associated with reduced risk of LADA in both HUNT and ESTRID. In ESTRID, stratification by GADA levels indicated that the reduced risk primarily pertained to LADA with low GADA levels (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.76–0.94 for every 5-gram increase in daily alcohol intake). Smoking was associated with a reduced risk of LADA in HUNT which we could not confirm in ESTRID; in contrast we found an increased risk of LADA in heavy smokers (OR; 1.37, 95% CI; 1.02-1.84). With regard to type 2 diabetes, we could confirm that alcohol intake is associated with a reduced risk and smoking with an increased risk. There was no association between moist snuff use and type 2 diabetes or LADA in either the Swedish (type 2 diabetes: OR for >10 box-years; 1.00, 95% CI; 0.47-2.11, and LADA: 1.01, 95% CI; 0.45-2.29) or the Norwegian study.

In conclusion, the results suggest that alcohol consumption reduces the risk of type 2 diabetes and type 2-like LADA. An increased risk of LADA was seen in smokers but results were contradictory and require further exploration. Finally the use of moist snuff was associated neither with type 2 diabetes nor LADA. These findings indicate that the etiology of LADA in part may be shared with type 2 diabetes and involve factors related to insulin sensitivity. Furthermore, they indicate that LADA may to some extent be preventable by lifestyle modification.

List of scientific papers

I. Rasouli B, Ahlbom A, Andersson T, Grill V, Midthjell K, Olsson L, Carlsson S. Alcohol consumption is associated with reduced risk of Type 2 diabetes and autoimmune diabetes in adults: results from the Nord-Trondelag health study. Diabet Med 2013;30:56-64.
https://doi.org/10.1111/j.1464-5491.2012.03713.x

II. Rasouli B, Andersson T, Carlsson PO, Dorkhan M, Grill V, Groop L, Martinell M, Tuomi T, Carlsson S. Alcohol and the risk for latent autoimmune diabetes in adults: results based on Swedish ESTRID study. Eur J Endocrinol 2014;171:535-543.
https://doi.org/10.1530/EJE-14-0403

III. Rasouli B, Grill V, Midthjell K, Ahlbom A, Andersson T, Carlsson S. 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. Diabetes Care 2013;36:604-610.
https://doi.org/10.2337/dc12-0913

IV. Rasouli B, Andersson T, Carlsson PO, Grill V, Groop L, Martinell M, Storm P, Tuomi T, Carlsson S. Smoking and the risk of LADA : results from a Swedish population-based case-control study. [Accepted]
https://doi.org/10.2337/dc15-2348

V. Rasouli B, Andersson T, Carlsson P.O, Grill V, Groop L, Martinell M, Midthjell K, Storm P, Tuomi T, Carlsson S. Use of Swedish moist snuff (snus) and the risk of type 2 diabetes and LADA: results based on two Scandinavian studies. [Submitted]