Diet and the risk of latent autoimmune diabetes in adults (LADA) : studies on the association with fish and sweetened beverages

Sammanfattning: Diabetes is an increasing public health problem affecting a breathtaking number of people worldwide. The knowledge about modifiable lifestyle factors influencing diabetes risk is extensive for type 2 diabetes, but limited for autoimmune forms of diabetes such as type 1 diabetes. Latent autoimmune diabetes in adults (LADA) is a hybrid form of diabetes with characteristics of both type 1 and type 2 diabetes. Diet has an important role in the development of type 2 diabetes but its role in autoimmune diabetes is largely unknown. The aim of this thesis was to study the risk of LADA in relation to intakes of fish and sweetened beverages, two commonly consumed foods hypothesized to play a role in the development of both type 1 and type 2 diabetes. Analyses were based mainly on ESTRID, a Swedish case-control study with incident cases of LADA and type 2 diabetes, and population-based controls. All participants in ESTRID were aged ≥ 35 years and LADA was defined by the presence of glutamic acid decarboxylase autoantibodies (GADA) and a level of C-peptide indicating remaining insulin secretion. Data on intakes of fish and sweetened beverages were available from questionnaires and investigated in relation to risk of LADA and type 2 diabetes. One study was based on data from EPIC-InterAct, a case-cohort study with prospective data from eight European countries. In EPIC-InterAct, we assessed the interaction of baseline GADA positivity and self-reported dietary fish or plasma n-3 PUFA in relation to the risk of adult onset diabetes. Based on ESTRID, weekly fatty fish intake was associated with 49% reduced risk of LADA (odds ratio [OR] 1.51, 95% confidence interval [CI] 0.30-0.87), whereas no association was found for type 2 diabetes (OR 1.01, 95% CI 0.74-1.39). These findings were supported by the results from EPIC-InterAct; low fatty fish intake was found to interact with GADA positivity on the risk of adult onset diabetes (attributable proportion due to interaction [AP] 0.48, 95% CI 0.24-0.72), and findings were similar for plasma n-3 PUFA. In ESTRID, sweetened beverage intake was positively associated with both LADA and type 2 diabetes. For LADA, the increased risk was evident only among carriers of low/intermediate risk HLA genotypes (OR per one daily serving 1.32, 95% CI 1.06-1.64). BMI was suggested to only partly mediate the associations between sweetened beverages and risk of LADA and type 2 diabetes, indicating that there may also be direct effects on glucose homeostasis. In conclusion, these results suggest that long-chain n-3 PUFAs from fish may decrease the risk of LADA whereas intake of sweetened beverages may increase the risk. Importantly, these findings indicate that diet may be a modifiable lifestyle factor influencing the development of LADA and hence be a target for preventive strategies.