Whole Organ Transplantation and Glucose Regulation

Abstract

Abstract:Pancreas transplantation has gained clinical acceptance since its initial application more than 30 years ago. A constellation of surgical, pharmacologic, and metabolic alterations occur with transplantation, particularly if pancreatic transplantation is performed in addition to renal transplantation in a uremic diabetic. Increasingly sophisticated studies have allowed analysis of the performance of the transplanted organ and have enhanced our basic understanding of insulin's complex interplay in peripheral glucoregulatory processes. Article:Clinical experience with pancreas transplantation was not overwhelmingly successful during the late 1960s and early 1970s [1]. Over the next 20 years a period of constant reevaluation and reassessment of early clinical failures resulted in the development of animal models of transplantation. These models ultimately led to advances in surgical techniques and immunosuppression therapy and provided a better understanding of the impact of surgically induced alterations to the pancreas on carbohydrate metabolism. As pancreas transplantation enjoyed an increasing success rate and longer patient survival, posttransplant graft physiology and the metabolic response to the new insulin source became an interesting area of research.EARLY MODELS OF TRANSPLANTATION Surgical alterations of the pancreas that occur during transplantation include (1) reduction of the beta cell mass (by resection, immunologic loss, or preservation ischemic loss); (2) systemic venous drainage versus portal venous drainage of the pancreatic venous effluent; and (3) denervation. Surgical alterations per se should lead to an altered insulin source. What effect, if any, might this have on peripheral levels of insulin or insulin's glucoregulatory properties? Would it ultimately affect the function of the transplanted pancreas? To address these questions and attempt to delineate the role of surgical alterations of the pancreas on longterm glucose homeostasis in transplanted patients, studies were performed using primarily dog or rat models. Reduction of Beta Cell MassThe complex interplay between insulin secretion and insulin action was suggested nearly 50 years ago by Dragstedt et al.'s observation that the amount of insulin required to control glucosuria after partial pancreatectomy exceeded the amount needed after complete pancreatectomy [2]. Subsequently, it became evident that surgical models of partial pancreatectomy might result in alterations of alpha and beta cell ratios, which could explain earlier observations. Studies evaluating a dog model of 60% to 80% partial pancreatectomy showed that these animals have a reduced insulin response to the intravenous glucose tolerance test (IVGTT) and altered potassium values, indicating altered glucose metabolism [3]. It was suggested that

Evolution of pancreas transplant surgery

“…However, experimental and clinical studies comparing hyperinsulinaemia and glucose metabolism after systemic and portal venous drainage have provided contradictory results 53–55 . In the setting of transplantation, the contribution of steroids and calcineurin inhibitors and to the peripheral resistance to insulin is not inconsiderable 53 .…”

“…52 However, experimental and clinical studies comparing hyperinsulinaemia and glucose metabolism after systemic and portal venous drainage have provided contradictory results. [53][54][55] In the setting of transplantation, the contribution of steroids and calcineurin inhibitors and to the peripheral resistance to insulin is not inconsiderable. 53 There is no convincing evidence to date of the metabolic advantages of portal venous drainage; the majority of pancreas units therefore prefer the technically simpler technique of systemic venous drainage.…”

Pancreatic Transplantation: Evaluation and Management

“…Overall improvement in quality of life and return to a more normal lifestyle are evident early on [15]. Pancreas transplantation may also be offered to carefully selected nonuremic type 1 dia-betic patients [16][17][18]. Pancreas transplantation should be considered as therapy only in patients who exhibit these 3 criteria: (1) a history of frequent, acute, and severe metabolic complications (hypoglycemia, hyperglycemia, ketoacidosis) requiring medical attention; (2) clinical and emotional problems with exogenous insulin therapy that are so severe as to be incapacitating; and (3) consistent failure of insulin-based management to prevent acute complications [13].…”