Clinical Outcomes and Insulin Secretion After Islet Transplantation With the Edmonton Protocol

Abstract

Islet transplantation offers the prospect of good glycemic control without major surgical risks. After our initial report of successful islet transplantation, we now provide further data on 12 type 1 diabetic patients with brittle diabetes or problems with hypoglycemia previous to 1 November 2000. Details of metabolic control, acute complications associated with islet transplantation, and long-term complications related to immunosuppression therapy and diabetes were noted. Insulin secretion, both acute and over 30 min, was determined after intravenous glucose tolerance tests (IVGTTs). The median follow-up was 10.2 months (CI 6.5–17.4), and the longest was 20 months. Glucose control was stable, with pretransplant fasting and meal tolerance–stimulated glucose levels of 12.5 ± 1.9 and 20.0 ± 2.7 mmol/l, respectively, but decreased significantly, with posttransplant levels of 6.3 ± 0.3 and 7.5 ± 0.6 mmol/l, respectively (P < 0.006). All patients have sustained insulin production, as evidenced by the most current baseline C-peptide levels 0.66 ± 0.06 nmol/l, increasing to 1.29 ± 0.25 nmol/l 90 min after the meal-tolerance test. The mean HbA_1c level decreased from 8.3 ± 0.5% to the current level of 5.8 ± 0.1% (P < 0.001). Presently, four patients have normal glucose tolerance, five have impaired glucose tolerance, and three have post–islet transplant diabetes (two of whom need oral hypoglycemic agents and low-dose insulin (r = 0.83, P < 0.001). Islet transplantation has successfully corrected labile type 1 diabetes and problems with hypoglycemia, and our results show persistent insulin secretion. After a minimum of 9,000 IEs per kilogram are provided, insulin independence is usually attained. An elevation of creatinine appears to be a contraindication to this immunosuppressive regimen. For the subjects who had labile type 1 diabetes that was difficult to control, the risk-to-benefit ratio is in favor of islet transplantation.