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

作者：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^*

来源：Diabetes Care, 2013, 36(11): 3483-3488.

DOI：10.2337/dc13-0128

OBJECTIVEPrevious work has shown a correlation between -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 -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 -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 %26lt;25% appeared from the receiver operating characteristic curve (0.97 [95% CI 0.93-1.00]). All patients with FBM %26gt;37% exhibited CVfg %26lt;25% and a %26gt;50% reduction of their pretransplant CVfg; this occurred in none with FBM %26lt;5%. Implants with FBM %26gt;18% reduced CVfg from a median pretransplant value of 46 to %26lt;25%.CONCLUSIONSGlucose clamping assesses the degree of restoration in FBM achieved by islet cell implants. Values %26gt;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.

• 出版日期2013-11