Pathogenesis of Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is considered a multifactorial, chronic, autoimmune disease in which autoreactive T-lymphocytes cause severe loss of pancreatic beta cells. Much progress has been done in the discovery of disease-predisposing genes, the identification of islet cell autoantigens, and key features of islet autoimmune responses. There is growing evidence for contributing environmental factors, including viruses, the microbiome, and dietary factors. Recent studies suggest that autoimmune-mediated beta cell destruction is likely the key pathogenic mechanism, but over a prolonged period of time, extending beyond clinical diagnosis. It is becoming evident that chronic beta cell inflammation is also a key component of the disease pathogenesis. Moreover, beta cell dysfunction is likely to precede and coexist with beta cell destruction, and it is emerging as a significant contributor to the onset of symptomatic diabetes. Thus, chronic islet inflammation and beta cell dysfunction should be considered critical therapeutic targets, together with improved immunoregulation. Growing evidence that beta cell destruction at diagnosis may only be partial in many patients is raising questions about the dynamics of the autoimmune process; the persistence of beta cells, insulin secretion, and disease activity for years after diagnosis point at the chronicity of T1D and suggest that therapeutic intervention to halt the disease process may be possible beyond the traditional, but arbitrary, immediate postdiagnosis period.