Revisiting multiple models of progression of β-cell loss of function in type 1 diabetes: Significance for prevention and cure.

Type 1 diabetes (T1D) results from a chronic autoimmune process that leads to β-cell destruction and exogenous insulin dependence. The natural history of T1D proposed by Eisenbarth suggested six relatively independent stages over the course of the entire disease process, which was considered to be linear and chronic. Based on this classical theory, immunotherapies aim to prevent or reverse all these periods of β-cell loss. Over the past 30 years, much novel information about the pathogenesis of T1D proved that there are complex metabolic changes occurring throughout the entire disease process. Therefore, new possible models for the natural history of the disease have been proposed; these models, in turn, may help facilitate fresh avenues for the prevention and cure of T1D. Herein, we briefly review recent findings in this field of research, with the aim of providing a better theoretical basis for clinical practice.