Pancreatic islet reserve in type 1 diabetes

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by pancreatic islet β cell loss and dysfunction resulting in insulin deficiency and hyperglycemia. During a presymptomatic phase of established β cell autoimmunity, β cell loss may first be evident through assessment of β cell secretory capacity, a measure of functional β cell mass. Reduction in pancreatic islet β cell reserve eventually manifests as impaired first‐phase insulin response to glucose and abnormal glucose tolerance, which progresses until the functional capacity for β cell secretion can no longer meet the demand for insulin to control glycemia. A functional β cell mass 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 β cell function 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. β cell replacement by islet transplantation can restore a physiologic reserve capacity for insulin secretion, confirming thresholds for functional β cell mass required for independence from insulin therapy. One goal of staging presymptomatic type 1 diabetes (T1D) is to enable early immune intervention strategies aimed at preventing or ameliorating symptomatic diabetes through preservation of sufficient pancreatic functional β cell mass to maintain (near)normoglycemia. Preservation of endogenous β cell function after clinical diagnosis is also important in facilitating optimal metabolic control. The objective of this review is to examine the physiological and clinical correlates of pancreatic islet reserve at each stage of T1D in order to aid understanding of pancreatic islet physiology informing interventions to maintain or restore a functional β cell mass.