Minimal Functional β-Cell Mass in Intraportal Implants That Reduces Glycemic Variability in Type 1 Diabetic Recipients

OBJECTIVE: Previous work has shown a correlation between β-cell number in cultured islet cell grafts and their ability to induce C-peptide secretion after intraportal implantation in C-peptide–negative type1 diabetic patients. In this cross-sectional study, we examined the minimal functional β-cell mass (FBM) in the implant that induces metabolic improvement. RESEARCH DESIGN AND METHODS: Glucose clamps assessed FBM in 42 recipients with established implants. C-peptide release during each phase was expressed as percentage of healthy control values. Its relative magnitude during a second hyperglycemic phase was most discriminative and therefore selected as a parameter to be correlated with metabolic effects. RESULTS: Recipients with functioning β-cell implants exhibited average FBM corresponding to 18% of that in normal control subjects (interquartile range 10–33%). Its relative magnitude negatively correlated with HbA(1c) levels (r = −0.47), daily insulin dose (r = −0.75), and coefficient of variation of fasting glycemia (CVfg) (r = −0.78, retained in multivariate analysis). A correlation between FBM and CVfg <25% appeared from the receiver operating characteristic curve (0.97 [95% CI 0.93–1.00]). All patients with FBM >37% exhibited CVfg <25% and a >50% reduction of their pretransplant CVfg; this occurred in none with FBM <5%. Implants with FBM >18% reduced CVfg from a median pretransplant value of 46 to <25%. CONCLUSIONS: Glucose clamping assesses the degree of restoration in FBM achieved by islet cell implants. Values >37% of normal control subjects appear needed to reduce glycemic variability in type 1 diabetic recipients. Further studies should examine whether the test can help guide decisions on additional islet cell transplants and on adjusting or stopping immunotherapy.