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 HbA1c 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 (<10 U/day). Three patients had a temporary increase in their liver-function tests. One patient had a thrombosis of a peripheral branch of the right portal vein, and two of the early patients had bleeding from the hepatic needle puncture site; but these technical problems were resolved. Two patients had transient vitreous hemorrhages. The two patients with elevated creatinine levels pretransplant had a significant increase in serum creatinine in the long term, although the mean serum creatinine of the group was unchanged. The cholesterol increased in five patients, and lipid-lowering therapy was required for three patients. No patient has developed cytomegalovirus infection or disease, posttransplant lymphoproliferative disorder, malignancies, or serious infection to date. None of the patients have been sensitized to donor antigen. In 11 of the 12 patients, insulin independence was achieved after 9,000 islet equivalents (IEs) per kilogram were transplanted. The acute insulin response and the insulin area under the curve (AUC) after IVGTT were consistently maintained over time. The insulin AUC from the IVGTT correlated to the number of islets transplanted, but more closely correlated when the cold ischemia time was taken into consideration (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.
- AIRg, acute insulin response to glucose
- AUC, area under the curve, AUCC-p, AUC for C-peptide above baseline
- AUCg, AUC for glucose above baseline
- AUCi, AUC for insulin above baseline
- CMV, cytomegalovirus
- HOMA, homeostasis model assessment
- IE, islet equivalent
- IGT, impaired glucose tolerance
- IVGTT, intravenous glucose tolerance test
- KG, the rate of glucose disposal
- OGTT, oral glucose tolerance test
- MAGE, mean amplitude of glycemic excursion
- WBC, white blood cell count
Address correspondence and reprint requests to Edmond A. Ryan, Department of Medicine, 362 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. E-mail:.
Received for publication 5 December 2000 and accepted in revised form 31 January 2001. Posted at www.diabetes.org/diabetes on 7 March 2001.