Minimal functional β-cell mass in intraportal implants that reduces glycemic variability in type 1 diabetic recipients

Pieter Gillard, Robert Hilbrands, Ursule Van de Velde, Zhidong Ling, Da Hae Lee, Ilse Weets, Frans Gorus, Christophe De Block, Leonard Kaufman, Chantal Mathieu, Daniel Pipeleers, Bart Keymeulen

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 HbA1c 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.

Original languageEnglish
Pages (from-to)3483-3488
Number of pages6
JournalDiabetes Care
Volume36
Issue number11
DOIs
Publication statusPublished - Nov 2013

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