Associations of type 2 diabetes mellitus with cancer and autoimmune diseases. A population-based epidemiological study in Sweden

Abstract: This thesis aimed to search for epidemiological evidence supporting the associations of type 2 diabetes mellitus (T2DM) with cancer and autoimmune diseases (ADs) by analysing several Swedish national registries. T2DM shares risk factors with cancer, such as obesity, diet, stress, and physical inactivity. However, it is unclear whether the associations with several types of cancers are due to shared risk factors, shared genes or metabolic disturbances of the underlying disease. Immunological data show that T2DM has autoimmune features, including the presence of autoantibodies against pancreatic β-cells and self-reactive T-cells. This doctoral project consists of four epidemiological cohort studies conducted using several population-based nationwide Swedish databases, which collectively contain information on socioeconomic status, comorbidities and demographics. We found that the risks of 24 cancers were increased in patients with T2DM, and that the highest risks were for liver cancer and pancreatic cancer. The cancer risks in siblings and spouses of individuals with T2DM were not increased. In addition, cancer patients with a previous T2DM diagnosis had a worse prognosis than those without T2DM, and the observed high cause-specific mortality in cancer patients with T2DM may be independent of age at cancer diagnosis and tumour stage. Prior diagnosis of T2DM in cancer patients was associated with an increased risk of dying from myocardial infarction, “other bacterial disease”, urinary system disease, hypertensive disease, and arterial disease. T2DM risk was increased after diagnosis of any one of 27 ADs, and the highest standardized incidence ratios (SIRs) were for chorea minor, lupoid hepatitis, and Addison’s disease. In conclusion, this project showed that pre-existing T2DM increased the subsequent risk of a range of site-/type-specific cancers, an effect that is potentially mediated by metabolic changes. Also, the mortality was increased in cancer patients with T2DM. In addition, the risk of T2DM was increased after many ADs suggesting that chronic inflammation-driven autoimmune activation may be a shared initiation mechanism for T2D and many ADs.