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Title
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Minimal functional -cell mass in intraportal implants that reduces glycemic variability in Type 1 diabetic recipients
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Author
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Abstract
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| 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 <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%.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. |
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Language
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English
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Source (journal)
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Diabetes care. - Alexandria, Va, 1978, currens
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Publication
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Alexandria, Va
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2013
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ISSN
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0149-5992
[print]
1935-5548
[online]
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DOI
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10.2337/DC13-0128
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Volume/pages
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36
:11
(2013)
, p. 3483-3488
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ISI
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000326274100023
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Full text (Publisher's DOI)
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