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Plasma GAD65, a Marker for Early beta-Cell Loss After Intraportal Islet Cell Transplantation in Diabetic Patients

Author:
  • Zhidong Ling
  • Pieter De Pauw
  • Daniel Jacobs-Tulleneers-Thevissen
  • Rui Mao
  • Pieter Gillard
  • Christiane S. Hampe
  • Geert A. Martens
  • Peter In't Veld
  • Åke Lernmark
  • Bart Keymeulen
  • Frans Gorus
  • Daniel Pipeleers
Publishing year: 2015
Language: English
Pages: 2314-2321
Publication/Series: Journal of Clinical Endocrinology and Metabolism
Volume: 100
Issue: 6
Document type: Journal article
Publisher: The Endocrine Society

Abstract english

Context and Objective: Intraportal islet transplantation can restore insulin production in type 1 diabetes patients, but its effect is subject to several interfering processes. To assess the influence of beta-cell loss before and during engraftment, we searched for a real-time marker of beta-cell destruction. Previous studies showed that 65-kDa isoform of glutamate decarboxylase (GAD65) is discharged by chemically damaged rat beta-cells. We therefore examined the utility of the GAD65 assay to detect and quantify destruction of human beta-cells in vitro and in vivo. Design and Participants: A time-resolved fluorescence immunoassay was used to measure GAD65 discharge from beta-cells after administration of toxins or after intraportal transplantation. The study in patients involved type 1 diabetes recipients of 56 implants. Results: GAD65 was discharged from cultured human beta-cells between 4 and 24 hours after acute insult and proportional to the number of dying cells. It was also detected in plasma during the first 24 hours after intraportal transplantation of human islet cell grafts. Diabetic nude rat recipients without hyperglycemic correction exhibited higher plasma GAD65 levels than those with normalization. In type 1 diabetes recipients of grafts with 2-5 x 10(6) beta-cells per kilogram of body weight, five of six with plasma GAD65 greater than 1 ng/mL failed to increase plasma C-peptide by greater than 0.5 ng/mL at posttransplant month 2, whereas five of six with undetectable plasma GAD 65 and 15 of 19 with intermediate levels did result in such increase. Conclusion: Plasma GAD65 qualifies as a marker for early beta-cell loss after intraportal transplantation. Further studies are needed to extend its clinical utility.

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Diabetes and Celiac Unit
  • ISSN: 1945-7197
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00