Dissertation

Infections, Antibiotics, Tobacco, Genetic Factors and Risk of Lada: Latent Autoimmune Diabetes in Adults, and Type 2 Diabetes

Edstorp, Jessica

2024

Overview

Diabetes is a spectrum of chronic diseases characterized by hyperglycaemia. Theaetiology and pathogenesis differ between types of diabetes, but all can lead tosevere complications. Latent autoimmune diabetes in adults (LADA) is the mostprevalent type of autoimmune diabetes with onset in adulthood, yet risk factorsare largely unknown. Therefore, this thesis was devoted to the study of potentialrisk factors for LADA compared to type 2 diabetes.The Swedish Epidemiological Study of Risk Factors for LADA and type 2 diabetes(ESTRID) constituted the foundation of the four studies in this thesis. ESTRID is acase-control study with incident cases of LADA and type 2 diabetes along withcontrol participants from the general population. Study I, II, and IV werecomplemented with incident cases of LADA and type 2 diabetes as well asdiabetes-free individuals from the Norwegian cohort study HUNT. Study I and IIinvestigated the role of tobacco use and genetic susceptibility for the risk of LADA,using data from ESTRID and HUNT. These analyses were supported by Mendelianrandomization studies based on data from genome-wide association studies. In Study III and IV, data from national and regional health registers were linked toESTRID and HUNT to investigate the association between LADA and priorinfections and antibiotic exposure. Results for LADA were compared to those fortype 2 diabetes in all four studies.We found that smoking increases the risk of LADA, particularly in those withgenetic susceptibility conferred by risk genes associated with autoimmunity, type2 diabetes, or insulin resistance. The increased risk of LADA and type 2 diabetesin smokers seen in the observational data was confirmed in the Mendelianrandomization studies. In contrast, no increased risk of LADA was observed withinfections or antibiotic exposure up to 10 years prior to diagnosis, neither in thosewith high genetic risk nor in those with low-moderate risk. Instead, a reduced riskassociated with antibiotic exposure 6-10 years prior to diagnosis was observed.In conclusion, tobacco use, which is associated with type 2 diabetes and insulinresistance, seems to increase the risk of LADA. Genetic susceptibility plays a roleby aggravating these associations. However, infections and antibiotic exposure,previously linked to type 1 diabetes, were not associated with LADA. Furtherstudies are needed to confirm these results, particularly the finding of a reducedrisk of LADA with prior exposure to antibiotics.

• Publisher: ProQuest Dissertations & Theses
• Subject: Insulin resistance / Mortality / Obesity / Pharmaceutical sciences / Public health / Viral infections / Virology
• ISBN: 9798384195085