title: Plasma GAD65, a Marker for Early β-Cell Loss After Intraportal Islet Cell Transplantation in Diabetic Patients.
abstract: 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 β-cell loss before and during engraftment, we searched for a real-time marker of β-cell destruction. Previous studies showed that 65-kDa isoform of glutamate decarboxylase (GAD65) is discharged by chemically damaged rat β-cells. We therefore examined the utility of the GAD65 assay to detect and quantify destruction of human β-cells in vitro and in vivo.
  
  
  METHODS
  A time-resolved fluorescence immunoassay was used to measure GAD65 discharge from β-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 β-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 × 10(6) β-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.
  
  
  CONCLUSIONS
  Plasma GAD65 qualifies as a marker for early β-cell loss after intraportal transplantation. Further studies are needed to extend its clinical utility.
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Zhidong
authors: Z
authors: Ling
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Pieter
authors: P
authors: De Pauw
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Daniel
authors: D
authors: Jacobs-Tulleneers-Thevissen
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Rui
authors: R
authors: Mao
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Pieter
authors: P
authors: Gillard
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Christiane S
authors: CS
authors: Hampe
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Geert A
authors: GA
authors: Martens
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Peter
authors: P
authors: In't Veld
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Åke
authors: Å
authors: Lernmark
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Bart
authors: B
authors: Keymeulen
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Frans
authors: F
authors: Gorus
authors: Diabetes Research Center and Universitair Ziekenhuis Brussel (Z.L., P.D.P., D.J.-T.-T., R.M., G.A.M., P.I.V., B.K., F.G., D.P.), Brussels Free University-VUB, B-1090 Brussels, Belgium; Department of Endocrinology (P.G.), Universitair Ziekenhuis Gasthuisberg, Katholieke Universiteit Leuven-KUL, B-3000 Leuven, Belgium; Department of Medicine (C.S.H.), University of Washington, Seattle, Washington 98109; and Department of Clinical Sciences (Å.L.), Lund University, Skåne University Hospital, SE-20502 Malmö, Sweden.
authors: Daniel
authors: D
authors: Pipeleers
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D016923:Cell Death; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000175:diagnosis / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D005968:Glutamate Decarboxylase / Q000097:blood*; D006085:Graft Survival; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D011169:Portal Vein; D011379:Prognosis; D051381:Rats; D011923:Rats, Nude; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D015415:Biomarkers; D013311:Streptozocin; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2