Plasma GAD65, marker for early beta cell loss following intraportal islet cell transplantation in diabetic patients

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 search for a real-time marker of beta-cell destruction. Previous studies showed that 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 following 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 following acute insult and proportional to the number of dying cells. It was also detected in plasma during the first 24 hours following 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) beta cells/kg BW, 5/6 with plasma GAD65 >1 ng/ml failed to increase plasma C-peptide by >0.5 ng/ml at post-transplant month 2, whereas 5/6 with undetectable plasma GAD 65 and 15/19 with intermediate levels did result in such increase.

CONCLUSION: Plasma GAD65 qualifies as marker for early beta cell loss following intraportal transplantation. Further studies are needed to extend its clinical utility.