Title: Minimal Functional β-Cell Mass in Intraportal Implants That Reduces Glycemic Variability in Type 1 Diabetic Recipients
Authors: Gillard, Pieter ×
Hilbrands, Robert
Van de Velde, Ursule
Ling, Zhidong
Lee, Da Hae
Weets, Ilse
Gorus, Frans
De Block, Christophe
Kaufman, Leonard
Mathieu, Chantal
Pipeleers, Daniel
Keymeulen, Bart #
Issue Date: Nov-2013
Publisher: American Diabetes Association
Series Title: Diabetes care vol:36 issue:11 pages:3483-8
Abstract: OBJECTIVEPrevious 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 METHODSGlucose 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.RESULTSRecipients with functioning β-cell implants exhibited average FBM corresponding to 18% of that in normal control subjects (IQR 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 (ROC) 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%.CONCLUSIONSGlucose 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.
ISSN: 0149-5992
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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