Islet transplantation in IDDM patients

Abstract

Several reports have already shown that intrahepatic transplantation of purified islets can replace the pancreatic endocrine function in diabetic patients without major side effects for either the patients or their liver function [1][2][3][4][5]. Despite these encouraging results, the data of the International Islet Transplant Registry [6] are not as encouraging: in the 1989-1994 period only 28 out of 180 patients (16 %) maintained insulin independence for more than one week.This paper reports the experience at one institute (San Raffaele Scientific Institute, University of Milan) with 21 cases of islet/kidney transplantations in insulin-dependent diabetic (IDDM) patients. The roles of islet mass and quality, immunosuppressive therapy and post-implantation management on the final outcome of fresh islet transplantation in IDDM patients are considered. Diabetologia (1997) Summary This single-centre study investigated parameters that positively correlated with the success rate after islet allotransplantation in insulin-dependent diabetic (IDDM) patients. Twenty-one intrahepatic, fresh islet transplantations were performed in 20 IDDM patients (one patient had two transplants), after or simultaneous with kidney transplantation. The correlation between number and purity of transplanted islets and final outcome was investigated. One patient died of a cardiac arrest several hours after islet transplantation; this patient was not included in the follow-up analysis. Three patients (15 %) experienced acute, irreversible, early failure of islet function, which was considered as a 'presumed rejection'. Nine patients (45 %) achieved either complete insulin-independence (seven cases) or a reduction (> 50 %) of exogenous insulin requirement (two cases), with sustained serum C-peptide secretion (0.89 ± 0.04 nmol/l; duration: 21 ± 7 months, range 2-58 months). Liver biopsy, performed 3 years after transplantation in one successful case, showed normal islets within the hepatic parenchyma. Eight cases (40 %) did not show any metabolic effect of islet transplantation, with low serum C-peptide levels ('presumed function exhaustion'). Metabolic investigations performed in successful cases showed an early phase of insulin release after arginine, mild and reversible postprandial hyperglycaemia and normal HbA 1c levels. Success of islet transplantation positively correlates with the number (p < 0.05) of the transplanted islets. Islet transplantation is a safe procedure, with 45 % success rate, in terms of insulin-independence or relevant reduction of exogenous insulin requirement, although success can be transient. [Diabetologia (1997) 40: 225-231]

Human Pancreatic Islets Produce and Secrete MCP-1/CCL2: Relevance in Human Islet Transplantation

“…Pancreata were obtained from heart-beating cadaveric multiorgan donors through the North Italian Transplant Organization. Islets were isolated according to a modification of the automated method (43,44). Samples of the pancreas and samples of isolated islets were taken for histological examination and for in vitro study.…”

“…Percutaneous trans-hepatic injection (under local anesthesia) was performed according to the protocol approved by the local ethics committee. All patients were already under immunosuppression therapy with steroids and cyclosporine for a previous kidney transplant (44). After islet transplantation, the therapy was changed as follows: antilymphocyte globulin (125 mg/day for 10 days; IMTIX, Marseille, France), cyclosporine (7.5 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), mycophenolate mofetil (2 g/day), and methylprednisone (500 mg immediately before surgery, 0.25 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 for 2 months after surgery, then lowered to 5 mg/day).…”

Kidney Function After Islet Transplant Alone in Type 1 Diabetes

“…Islets were cultured in M199 medium supplemented with 10% FCS, 1% L-glutamine, 100 units/ml penicillin, and 100 g/ml streptomycin and incubated at 30°C in 5% CO 2 and 95% humidified air for 2-48 h. Islets were tested for sterility, endotoxin (Chromogenic LAL test; BioWhittaker, Walkersville, MD), and Mycoplasma (Mycoplasma detection kit; Boehringer Mannheim, Indianapolis, IN). Islets were infused in the liver according to the protocol approved by our institutional review board, as reported previously (18,19). In brief, an ultrasound imager was used for guidance during portal vein puncture with a 22-gauge needle under local anesthesia.…”

Metabolic Effects of Restoring Partial β-Cell Function After Islet Allotransplantation in Type 1 Diabetic Patients

“…Diabetes 50:277-282, 2001 W e have recently shown that successful intraportal islet transplantation can normalize hepatic glucose production and insulin action in type 1 diabetic patients with a kidney transplant (1). This procedure, now performed in several centers worldwide (2)(3)(4)(5)(6), is relatively safe, noninvasive (percutaneous puncture of the liver), and repeatable. The major factors limiting the large-scale application of islet graft in diabetic patients receiving chronic immunosuppression for a kidney graft are 1) the low percentage of patients reaching insulin independence and a complete normalization of glucose homeostasis (1) and 2) the limited survival of fully successful grafts.…”

“…The major factors limiting the large-scale application of islet graft in diabetic patients receiving chronic immunosuppression for a kidney graft are 1) the low percentage of patients reaching insulin independence and a complete normalization of glucose homeostasis (1) and 2) the limited survival of fully successful grafts. Most diabetic patients receiving an islet graft achieve only partial function and a reduction of the pretransplant insulin requirement (2-6); they are characterized by fasting C-peptide concentrations in the near-normal range, but frankly abnormal fasting glucose and GHb values (1)(2)(3)(4)(5)(6). In the last decade, we (7-10) and others (11,12) found that protein and lipid metabolism had greater sensitivity to acutely infused insulin than did glucose metabolism, both in diabetes and uremia.…”