Aspects of autoimmune diabetes: markers, treatment and relation to thyroid dysfunction

Abstract

Autoimmune diabetes is a complex disease in many respects. Complexity includes etiology and progression, the clinical picture, which differs between debut in childhood and adulthood, the association of autoimmune diabetes with other autoimmune diseases and the optimal treatment of the disease at a stage when insulin therapy is not necessary by clinical judgment. Reflecting these aspects of autoimmune diabetes the aim of this thesis was to provide relevant information on 1) circulating immune mediators in autoimmune diabetes and 2) the association of diabetes with autoimmune thyroid dysfunction. Lastly, 3) we provide data on a clinical trial which tests different treatments in patients with a subform of autoimmune disease diagnosed at adult age, called latent autoimmune diabetes in adults (LADA). - In paper I we measured prospectively circulating immune mediators in individuals with new onset autoimmune diabetes, with a mean age of 28 years. Baseline data were compared with those of age-matched non-diabetic controls. We find that circulating immune mediators were stable over time in adult-onset type 1 diabetes. Associations between different immune mediators were strikingly, but not exclusively, linked to autoimmune diabetes. Adipose mass, reflected by BMI, turned out to be a major confounder for associations of immune mediators with autoimmunity. - In paper II we analyzed data on diabetes and thyroid disorders out of data accessible from HUNT2 and HUNT3, i.e. from the two latest surveys of the HUNT Study. We found a strong association between autoimmune diabetes and increased prevalence of hypothyroidism and hyperthyroidism. Further, the increase in prevalence of hypo- and hyperthyroidism associated with autoimmune diabetes appeared gender neutral. On the other hand there was no clear association between type 2 diabetes and hypothyroidism or hyperthyroidism. The lack of association contradicts the notion that increased surveillance of thyroid function is necessary in type 2 diabetes. - In paper III we analyzed baseline data from an ongoing study in LADA patients comparing early insulin vs. traditional peroral treatment, remaining beta cell function being the main outcome. In 44 patients randomized into the study we found that important baseline characteristics were well-balanced between the two randomized treatment groups. Further, the clinical profile of the study population seemed representative for a larger population. These findings appear favorable for eventually arriving at an unambiguous interpretation of the beta cell outcome variables.