Evidence for Residual and Partly Reparable Insulin Secretory Function and Maintained β-Cell Gene Expression in Islets From Patients With Type 1 Diabetes.

Abstract

It is commonly accepted that type 1 diabetes (T1D) is an autoimmune and inflammatory disease that results from the wholesale yet surprisingly selective killing of the insulin-secreting β-cells of pancreatic islets (1–4). While the relative importance of reduced β-cell function versus reduced β-cell mass is currently debated in type 2 diabetes (5), T1D has been considered the classic example where diabetes results from reduced β-cell mass secondary to autoimmune attack (1,3,4,6). However, this view has recently been challenged (2,6–9). In this issue of Diabetes , Krogvold et al. (10) compare residual glucose-dependent insulin secretion and whole-genome RNA sequencing of islet tissue from donors with and without diabetes. Islets were obtained from adult T1D subjects soon after the onset of the disease. Recent studies have shown that residual plasma C-peptide levels are present long after the onset of diabetes in patients with T1D (1,6,11–14). However, it is unknown whether this low level of insulin production represents secretion from β-cells that have somehow survived autoimmune attack, perhaps because the autoimmune process was halted or because not all of the β-cells were equivalently affected, or whether they represent a newly regenerated β-cell subpopulation (2). A third possibility is that the surviving β-cells, being in the minority, may simply represent the tail end of the normal distribution of islets originally residing in the pancreas (15). Finding residual C-peptide secretion is …