(36f) Revisiting Beta Cell Destruction At The Onset Of Type 1 Diabetes Mellitus

Type 1 diabetes mellitus is characterized by an inability to produce endogenous insulin. Based on a series of histopathology studies, it is commonly stated that the onset of clinical symptoms of glucose dysregulation in humans corresponds to an 80-95% reduction in beta cell mass. In contrast, more recent studies suggest that onset occurs at a significantly lower reduction in endogenous insulin production. Motivated by this conflicting data, a meta-analysis was used to re-examine these landmark histopathology studies. The histopathology results identifying insulin containing islets were extracted from the literature. The results for patient population were stratified by duration of diabetic symptoms and age at onset. Regression was used to determine the dependence of residual beta cell mass to age at onset. Using a Markov Chain Monte Carlo algorithm, a Bayesian analysis was used to assess how combining these different studies into a composite data set impacted the inferential statistics. Patients who died within three weeks of diagnosis for Type 1 diabetes exhibited significant heterogeneity in residual beta cell mass. The percentage reduction in beta cell mass was highly correlated with the age of onset with the greatest reduction in beta cell mass in the youngest patients. Given the constant lifetime risk for developing Type 1 diabetes mellitus, the trend identified by the meta-analysis suggests that severe impairment in beta cell function or decreased insulin sensitivity may play an increasing role as patients, at risk for developing Type 1 diabetes mellitus, age.