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.
Keywords: insulin secretion; pancreatic islet; type 1 diabetes; α cell; β cell.
© 2021 New York Academy of Sciences.