Epidemiological aspects of type 1 diabetes : early life origins, childhood comorbidities, and adult outcomes

• Type 1 diabetes is an autoimmune disease, often with onset during childhood, that requires lifelong insulin therapy due to the loss of pancreatic beta-cells. Several aspects of type 1 diabetes epidemiology remained to be explored and were the focus of this thesis. To begin, environmental risk factors in childhood play an important role in triggering the onset of disease, especially in genetically high-risk individuals but less was known of the early life origins related to maternal stress during pregnancy. Next, the comorbidity between type 1 diabetes and asthma or allergic diseases had long been debated but evidence stood inconclusive. Lastly, while many long-term outcomes of type 1 diabetes in adulthood had been demonstrated, the effect of glycaemic control on final adult height was not yet known. The aim of this thesis was therefore to address these knowledge gaps regarding epidemiological aspects of type 1 diabetes by investigating maternal depression or anxiety during pregnancy as a risk factor, furthering the understanding of the comorbidity with asthma or other allergic diseases, and examining the effect of glycaemic control on adult height. To study these associations on a population-based scale, linkages of healthcare and sociodemographic data from nationwide registers in Sweden were utilised alongside genetic information from the Swedish Twin Registry and clinical measurements from the National Diabetes Register. Paper I identified maternal depression or anxiety during pregnancy as a risk factor for offspring type 1 diabetes. The findings did not seem to be entirely explained by familial confounding from shared genes or environment. Paper II demonstrated the co-occurrence of asthma and type 1 diabetes in individuals, the importance of the sequential appearance of the diseases with previous asthma increasing the risk of subsequent type 1 diabetes, and the familial co-aggregation among full siblings and cousins pointing to the importance of shared familial factors. Paper III expanded on these findings by also displaying associations between type 1 diabetes and other allergic diseases (allergic rhinitis or eczema). Familial co-aggregation of allergic rhinitis and type 1 diabetes suggested a shared liability, in contrast to the lack of such associations for eczema. No signs of a large genetic overlap between type 1 diabetes and asthma or any other allergic disease were found. Paper IV uncovered differences in final adult height depending on glycaemic control in children and adolescents with type 1 diabetes. Having poor glycaemic control with a mean haemoglobin A1c >75 mmol/mol was associated with lower adult height in both males and females and an increased risk of short stature (adult height below -2 standard deviations) in males.

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