β-Cell Secretory Capacity Predicts Metabolic Outcomes Over 6 Years After Human Islet Transplantation

Abstract

Transplanted islet functional β-cell mass is measured by β-cell secretory capacity derived from the acute insulin response to glucose-potentiated arginine (AIRpot); however, data are limited beyond 1 year posttransplantation for individuals with type 1 diabetes. We evaluated changes in β-cell secretory capacity in a single-center longitudinal analysis and examined relationships with measures of islet cell hormone metabolism and clinical measures of graft function (mixed-meal tolerance test [MMTT] C-peptide, BETA-2 score, and continuous glucose monitoring [CGM]). Eleven individuals received purified human pancreatic islets over one or two intraportal infusions to achieve insulin independence and were observed over a median of 6 (interquartile range 5-7) years. β-Cell secretory capacity remained stable over 3 years before declining. Fasting glucagon and proinsulin secretory ratios under glucose potentiation were inversely correlated with AIRpot. A functional β-cell mass of 40% normal predicted insulin independence and was strongly predicted by ratio of MMTT C-peptide to glucose and BETA-2 score. A functional β-cell mass of >20% normal predicted excellent glycemic outcomes, including ≤1% time in range <60 mg/dL, ≤2% time in range >180 mg/dL, and ≥90% time in range 70-180 mg/dL. β-Cell replacement approaches should target a functional β-cell mass >40% normal to provide sufficient islet reserve for sustained insulin independence. Ratio of MMTT C-peptide to glucose and BETA-2 score can inform changes in functional β-cell mass in the clinical setting.