Results of a Multi-Year Comparison of Islet Transplantation With Intensive Medical Therapy on the Progression of Microvascular Complications in Type 1 Diabetes

Abstract

8 5 MONDAY their last infusion. Key changes from baseline to one year after last infusion were: HbA1c declined from 7.7+1.3% (mean+SD) to 6.2+0.9; C-peptide increased from 0.1+0.2 ng/mL to 1.3+1.1; and the proportion experiencing severe hypoglycemia events (80% pre-transplant) declined to 10%. About one-third of the recipients experienced one or more serious adverse events that were deemed related to either procedural or immunosuppression factors. In all but 14 patients, these events resolved without complications. One of the fi ve reported deaths was due to viral meningitis. Ten cases of neoplasm were reported. Conclusions: Islet transplantation in 1999-2007 represents a promising procedure for vastly improving glycemic control and nearly eliminating severe hypoglycemia. Procedural complications have been virtually eliminated. Undesirable effects of immunosuppression need to be balanced against the benefi ts of the procedure. The registry is growing large enough to begin identifying factors that affect success and identify the patients best suited for islet transplantation. The British Columbia Islet Transplant Program is conducting a prospective, crossover, cohort study comparing intensive medical therapy and islet cell transplantation (ICT) on the progression of diabetic retinopathy, nephropathy and neuropathy. A cohort of 44 patients was enrolled between January 2002 -January 2005. All patients began intensive medical therapy upon enrollment and then crossed-over to transplantation when an appropriate donor became available. Patients received immunosuppression with ATG induction, followed by tacrolimus and mycophenylate together with > 12,000 islet equivalents (IE) /kg from 1 -4 donors. 31 patients received 64 islet infusions. They were followed for an average duration of 39 months post-ICT and 37 months for medical treatment. Analysis was by intention to treat and endpoints were prespecifi ed before the study began. We present an interim analysis of outcomes. Comparison of median HbA1c (%) for all subjects showed 7.5±1.2 for medical versus 6.7±0.9 for ICT (p<0.01). Retinopathy was assessed using 7-fi eld stereo fundus photography and graded using the international scale. Progression was defi ned as nonproliferative retinopathy advancing by 1 or more levels or proliferative retinopathy reaching a severity that qualifi ed for laser treatment. Progression occurred signifi cantly more often in subjects on medical therapy (10/82 eyes) than after ICT (0/51 eyes) (p < .01). Considering only ICT subjects, progression occurred in 6/51 eyes while on medical treatment than post ICT (0/51) (p < .02). The primary endpoint for nephropathy was rate of change in GFR measured by blood clearance of 99mTc-DPTA measured every 6 months. GFR values were analysed by linear regression to calculate the rate of change for each subject. Individual patient results were combined to determine the mean intrapatient rate of change in GFR. Change in GFR did not differ for ICT (-3.8 ± 12.7 ml/ min/yr) compared with medical (-5.1 ± 8.4). Both...

Mechanistic Insights into Ferroptotic Cell Death in Pancreatic Islets

“…The transplantation of pancreatic islets into the liver represents a therapeutic strategy mainly for patients with type 1 diabetes (T1D) experiencing life-threatening hypoglycemic situations despite optimal diabetes therapy or, in the case of an autologous transplantation setting, to prevent patients undergoing (sub-)total pancreatectomy from iatrogenic diabetes 5 7 8 . The intraportal transplantation of pancreatic islets is less invasive than a complete pancreas transplantation but has comparable effects on the stabilization of glycemic control and diabetes-associated complications 8 9 . However, it is estimated that nearly 70% of the islet graft is lost during the peri- and post-transplant period 10 .…”