Impact of Islet Transplantation on Diabetes Complications and Quality of Life

Abstract

Insulin represents a life-saving therapy for patients with type 1 diabetes but, despite appropriate treatment, it prevents only partially long-term diabetic complications, while generating fatal hypoglycemic episodes. Islet transplantation gained attention because of its safety, effectiveness, and minimal invasiveness; however it remains a procedure reserved for a selected group of patients. The introduction of the Edmonton Protocol in 2000, based on a newly designed steroid-free immunosuppressive protocol, revamped the course of islet transplantation. The main goal of islet transplantation remains insulin independence, although the effect of islet transplantation can be more comprehensively evaluated in terms of frequency of hypoglycemic episodes and impact on diabetic complications and quality of life. Islet transplantation was shown to have positive consequences on cardiovascular, renal, neurologic, and ocular diabetic complications. The proof of concept for cellular replacement therapy in diabetes has been established with islet transplantation, it only needs to be improved and rendered widely available.

Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in New-Onset Type 1 Diabetes: A Multicenter Analysis

“…Conversely, while both islet cell transplantation and treatment with anti-CD3 mAbs are considered relatively safe, they have been shown to achieve insulin independence in only a very few subjects at 5 years of follow-up (25% and 5%, respectively) (9). Despite this, islet cell transplantation has been very successful in halting the progression of both short-term and long-term complications of T1D (19,20). Our analysis demonstrates that AHSCT in individuals with T1D achieved insulin independence in 59% of subjects at 6 months, and it was maintained in 32% of subjects at the last time point of their follow-up.…”

Small Islets Transplantation Superiority to Large Ones: Implications from Islet Microcirculation and Revascularization

“…However, administration of insulin is onerous for the patients. And most importantly, due to the breach of the closed dynamic regulation loop in response to physiological changes, it is difficult for exogenous insulin formulations to avoid episodes of hyperglycemia and hypoglycemia [5]. As first introduced by the Edmonton protocol in the year of 2000, pancreatic islet transplantation (PIT) emerged as a promising method to normalize metabolic control in a way that cannot be achieved with exogenous insulin [6–8].…”

Validity of animal models of type 1 diabetes, and strategies to enhance their utility in translational research

“…Cell-based therapy, i.e., replacement of the defective insulinproducing pancreatic β-cells generally described as islet transplantation, is one approach that has shown remarkable promise in the clinic in restoring normoglycemia and reducing long-term diabetes complications such as retinopathy, nephropathy, neuropathy and peripheral vascular disease (Barton et al, 2012;Bassi and Fiorina, 2011;Cure et al, 2008;Figliuzzi et al, 2013;Thompson et al, 2011;Warnock et al, 2008). The clinical introduction followed studies on islet allotransplantation in a rat model and then in a rhesus macaque model providing successful proofof-concept data (Ballinger et al, 1972;Ricordi et al, 1992b;Scharp et al, 1975Scharp et al, , 1990.…”