Pancreatic islet reserve in type 1 diabetes.

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by pancreatic islet βcellloss and dysfunction resulting in insulin deficiency and hyperglycemia. During a presymptomatic phase of established β cell autoimmunity, βcellloss may first be evident through assessment of βcellsecretory capacity, a measure of functional βcellmass. Reduction in pancreatic islet βcellreserve eventually manifests as impaired first-phase insulin response to glucose and abnormal glucose tolerance, which progresses until the functional capacity for βcellsecretion can no longer meet the demand for insulin to control glycemia. A functional βcellmass of ∼25% of normal may be required to avoid symptomatic T1D but is already associated with dysregulated glucagon secretion. With symptomatic T1D, stimulated C-peptide levels >0.60 ng/mL (0.200 pmol/mL) indicate the presence of clinically meaningful residual βcellfunction for contributing to glycemic control, although even higher residual C-peptide appears necessary for evidencing glucose-dependent islet β and α cell function that may contribute to maintaining (near)normal glycemia. βcellreplacement by islet transplantation can restore a physiologic reserve capacity for insulin secretion, confirming thresholds for functional βcellmass required for independence from insulin therapy.