Normoglycaemia after transplantation of freshly isolated and cryopreserved pancreatic islets in Type 1 (insulin-dependent) diabetes mellitus

Abstract

Purified islets of Langerhans and a kidney were transplanted into a 36-year-old patient who suffered from renal failure secondary to a 25 year history of Type 1 (insulin-dependent) diabetes mellitus. The islet graft contained 243,000 fresh islets (mean islet diameter 150 microns) that were syngeneic with the kidney graft and 368000 cryopreserved islets that had been collected from four other donors. The total of 10,000 islets/kg body weight was infused into the liver via the umbilical vein. Immunosuppression was induced with antilymphocyte globulin and maintained with prednisone, cyclosporine and azathioprine. Serum C-peptide levels (ng/ml) during fasting and after standard mixed meal feeding (Sustacal) were less than 0.12 preoperatively. Postoperatively, insulin secretion was restored: fasting C-peptide rose during the first 4 weeks to levels of 4 to 5 and Sustacal elicited a further rise to 6 to 7. Transplant renal function was stable. Daily fasting glucose (mmol/l, mean +/- SD) was 5.6 +/- 1 and 5.3 +/- 0.6 during the first and second months respectively and post-Sustacal glucose was 5.7 +/- 0.8. Exogenous insulin therapy was progressively withdrawn and stopped during the ninth week. Thereafter, fasting glucose was 4.7 +/- 0.5, 24 h mean glucose was 6.6 +/- 0.5, and normoglycaemia was maintained after Sustacal. These data show that this mass of freshly isolated and cryopreserved islets from multiple donors provided sustained function (3 months) that reversed insulin-dependence in an immunosuppressed Type 1 diabetic patient treated with simultaneous islet-kidney transplantation.