Type 1 diabetes: translating mechanistic observations into effective clinical outcomes

Abstract

Summary Type 1 diabetes remains an important health problem, particularly in Western countries where the incidence has been increasing in younger children1. In 1986, Eisenbarth described Type 1 diabetes as a chronic autoimmune disease. Work over the past 3 ½ decades has identified many of the genetic, immunologic, and environmental factors that are involved in the disease and have led to hypotheses concerning its pathogenesis. Based on these findings, clinical trials have been conducted to test these hypotheses but have had mixed results. In this review, we discuss the findings that have led to current concepts of the disease mechanisms, how this understanding has prompted clinical studies, and the results of these studies. The findings from preclinical and clinical studies support the original proposed model for how type 1 diabetes develops, but have also suggested that this disease is more complex than originally thought and will require broader treatment approaches.

Prolonged insulin treatment sensitizes apoptosis pathways in pancreatic β cells

“…Loss of pancreatic β-cells is a major contributing factor to decreased pancreatic function in both type 1 (T1D) (Herold et al 2013) and at a later stage in type 2 (T2D) diabetes (Allagnat et al 2012). Infiltrating T and B cells and macrophages in T1D release reactive oxygen and nitrogen radicals and destroy β cells (Hou et al 2008).…”

Emerging roles of GLIS3 in neonatal diabetes, type 1 and type 2 diabetes

“…Common T1D is an autoimmune disorder that arises from the action of a combination of genetic and environmental factors (Herold et al 2013). More than 50 regions of the human genome have been identified to confer the susceptibility for common T1D ).…”

The Immune Pathogenesis of Type 1 Diabetes: Not Only Thinking Outside the Cell but Also Outside the Islet and Out of the Box

“…An abnormally high proliferation of intrapancreatic local myeloid precursors (18). It must be noted that in NOD mice myeloid bone marrow precursors (19), other myeloid lineages (microglia [20]), and T cells also show extensive intrinsic abnormalities in growth and development (1,21). Do parenchymal cells in NOD mice and patients with type 1 diabetes share the same molecular aberrancies, leading to abnormalities in growth and development?…”