Endocrine Secretory Reserve in Recipients of Islet of Langerhans Versus Whole Pancreas Transplants

Abstract

Introduction: Islet of Langerhans and pancreas transplantation are two options for the treatment of type 1 diabetes. In islet transplantation, islets are transplanted into the liver, and insulin is released directly into the microenvironment of its major target organ. To date, no study has compared the metabolic responses of pancreas versus islet transplant recipients. Methods: We performed a cross-sectional study of 15 islet (ISL) and 29 pancreas (PAN) transplant recipients. All grafts had function. All pancreas Tx had systemic venous drainage. Healthy subjects (CON) served as controls. PAN patients had a mean age of 48±7 years and a post-transplant follow-up of 7±4 years. ISL recipients had a mean age of 53±10 years and a post-transplant follow-up of 7±4 years. All subjects were administered an intravenous arginine stimulation test, and insulin (I), C-peptide, total (TP) proinsulin levels were determined from serum samples. Acute insulin response (AIR) and rates of insulin processing (=I/(TP+I)) were calculated. Results: PAN subjects had better HbA1c and fasting glycemia than insulin-independent ISL patients (II-ISL, n=9). Basal insulin and C-peptide levels were higher in PAN group than in control and II-ISL groups, because of systemic drainage. II-ISL patients had similar basal insulin and C-peptide levels than controls. AIR were 27±15, 144±104, 324±144, 252±189 pmol/l for ID-ISL, II-ISL, PAN and CON subjects respectively (II-ISL vs PAN or ID-ISL: p< 0.05, and p=0.13 vs CON). Basal I/(TP+I) ratios were higher in PAN and II-ISL groups than in CON group (82%, 86% and 60% respectively). After arginine stimulation, all groups had elevated processing rates (93%). Conclusions: These data suggest that insulin-independent islet transplant recipients can have similar basal metabolic parameters than healthy controls, at the cost of a higher rate of proinsulin processing. Higher responses of pancreas transplant recipients are likely a reflection of systemic venous drainage of endocrine secretions.