Metabolic abnormalities in the pathogenesis of type 1 diabetes

Abstract

Clinical onset of type 1 diabetes (T1D) is thought to result from a combination of overt beta cell loss and beta cell dysfunction. However, our understanding of how beta cell metabolic abnormalities arise during the pathogenesis of disease remains incomplete. Despite extensive research on the autoimmune nature of T1D, questions remain regarding the time frame and nature of beta cell destruction and dysfunction. This review focuses on the characterizations of beta cell dysfunction in the prediabetic and T1D human and mouse model. Studies have shown evidence supporting progressive loss of beta cell mass and function prior to T1D onset, while other scientists argue beta cell destruction occurs later in the disease process. Determining the time frame of beta cell destruction and identifying metabolic mechanisms that drive beta cell dysfunction has high potential for successful interventions to maintain insulin secretion for individuals with established T1D as well as those with prediabetes.

Figure 1

nPOD cases with insulin positive islets have a later age of onset (A) and a shorter duration of disease (B) when compared to cases without insulin positive islets. This figure contains data from all of the cases within nPOD (n=100 as of April 1, 2014) that are classified as donors with T1D (n=88; 31 had insulin positive islets by immunohistochemistry) and T1D Medalist (n=12; 3 had insulin positive islets by immunohistochemistry). T1D Medalists appear as an X in each graph. These publically available data were obtained from the nPOD Aperio Spectrum database (http://ahc-path-apr01.ahc.ufl.edu/).