Clinical outcomes and insulin secretion after islet transplantation with the edmonton protocol

Islet transplantation offers the prospect of good glycemic control without major surgical risks. After our initial report of successful islet transpla ntation, we now provide further data on 12 type 1 diabetic patients with br ittle diabetes or problems with hypoglycemia previous to 1 November 2000. D etails of metabolic control, acute complications associated with islet tran splantation, and long-term complications related to immunosuppression thera py and diabetes were noted. Insulin secretion, both acute and over 30 min, was determined after intravenous glucose tolerance tests (IVGTTs). The medi an 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-s timulated glucose levels of 12.5 +/- 1.9 and 20.0 +/- 2.7 mmol/l, respectiv ely, 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 sustai ned insulin production, as evidenced by the most current baseline C-peptide levels 0.66 <plus/minus> 0.06 nmol/l, increasing to 1.29 +/- 0.25 nmol/l 9 0 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, f our patients have normal glucose tolerance, five have impaired glucose tole rance, 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 thrombo sis of a peripheral branch of the right portal vein, and two of the early p atients had bleeding from the hepatic needle puncture site; but these techn ical problems were resolved. Two patients had transient vitreous hemorrhage s. The two patients with elevated creatinine levels pretransplant had a sig nificant increase in serum creatinine in the long term, although the mean s erum creatinine of the group unchanged. The cholesterol increased in five p atients, and Lipid-lowering therapy was required for three patients. No pat ient has developed cytomegalovirus infection or disease, posttransplant lym phoproliferative disorder, malignancies, or serious infection to date. None of the patients have been sensitized to donor antigen. In 11 of the 12 pat ients, insulin independence was achieved after 9,000 islet equivalents (IEs ) per kilogram were transplanted. The acute insulin response and the insuli n area under the curve (AUC) after IVGTT were consistently maintained over time. The insulin AUC from the IVGTT correlated to the number of islets tra nsplanted, but more closely correlated when the cold ischemia time was take n into consideration (r = 0.83, P < 0.001). Islet transplantation has succe ssfully corrected labile type 1 diabetes and problems with hypoglycemia, an d our results show persistent insulin secretion. After a minimum of 9,000 I fs per kilogram are provided, insulin independence is usually attained. An elevation of creatinine appears to be a contraindication to this immunosupp ressive regimen. For the subjects who had labile type 1 diabetes that was d ifficult to control, the risk-to-benefit ratio is in favor of islet transpl antation.