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Diabetes Progress of Islet Transplantation over the Last 15 Years Mohammed Almehthel, MD, CCD, ABIM, FRCPC, 1 Breay W Paty, MD, FRCPC 2 and David M Thompson, MD, FRCPC 2 1. Clinical Assistant Professor; 2. Clinical Associate Professor, University of British Columbia, Vancouver, Canada Abstract Diabetes mellitus prevalence is increasing worldwide. Type 1 diabetes (T1DM), which is caused mainly by autoimmune destruction of beta cells, accounts for approximately 5–10 % of all diabetes. Intensive glycemic control has been shown to reduce complications of T1DM. However, this has been difficult to achieve and is usually associated with frequent hypoglycemia. Islet transplantation (IT) has emerged as an acceptable method for the treatment of patients with T1DM who suffer for frequent severe hypoglycemia and/or glycemic lability. Although initial success was limited, improvement in IT has been observed over the last 15 years. The 5-year insulin independence rate approaches 30–50 % in some experienced centers. Even without achieving insulin independence, IT has significant benefits including prevention of hypoglycemia, stabilization of glycemic control, reduction in some complications of diabetes, and improvement in quality of life. Here, we provide a brief review on IT including its history, selection of IT candidates, description, and complications of the procedure and outcomes. Keywords Type 1 diabetes, islet transplantation, brittle diabetes, beta cells, pancreas Disclosure: Mohammed Almehthel, MD, CCD, ABIM, FRCPC, Breay W Paty, MD, FRCPC, and David M Thompson, MD, FRCPC, have no conflicts of interest to declare. No funding was received for the publication of this article Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: September 1, 2015 Accepted: September 30, 2015 Citation: US Endocrinology 2015;11(2):70–4 Correspondence: Mohammed Almehthel, MD, CCD, ABIM, FRCPC, Clinical Assistant Professor, University of British Columbia, 4102-2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada. E: Diabetes mellitus (DM) is a global epidemic. 1 In 2013, there were 382 million people with DM, and this number is expected to rise to 592 million by 2035. 2 Type 1 diabetes (T1DM), which is caused mainly by an autoimmune- mediated destruction of beta cells within the islet of Langerhans, accounts for 5–10 % of the total cases of diabetes worldwide. 3 Glycemic control is the cornerstone of diabetes care. The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive glycemic control reduces the long-term complications of hyperglycemia in T1DM. 4 However, diabetic complications continue to be a significant burden in persons with T1DM. 5 Additionally, intensive blood glucose control often comes at the cost of increased rate of hypoglycemia. 6,7 The improvement in glycemic control was associated with a two- to sixfold increase in severe hypoglycemia in the intensive treatment arm of the DCCT. 8 However, it is often challenging to attain or sustain target hemoglobin A 1c (HbA 1c ) of less than 7 %, especially in patients who are at risk for hypoglycemia. In the Epidemiology of Diabetes Intervention and Complication (EDIC) study, the difference in mean HbA 1c between the two original DCCT treatment groups has become statistically indistinguishable (around 8 %) during the most recent years of follow-up. 9 Analysis of the National Health and Nutrition Examination Survey (NHANES) data collected between 1999 and 2000 indicated that only 37.0 % of adults with diagnosed DM in the US achieved a HbA 1c below 7 %. 10 Many innovations have been developed to improve the management of T1DM, including insulin pumps, continuous glucose monitoring systems 70 (CGMS), and semi-closed loop systems. However, despite these innovations, the effective care of patients with diabetes remains challenging, with a significant proportion still suffering from hypoglycemia and long-term complications of diabetes. This has led to the efforts to preserve or restore endogenous beta cell mass, which could provide better glycemic control and help prevent long-term complications of diabetes. Whole pancreas transplantation is a successful approach to treat T1DM. However, it is still associated with significant morbidity and mortality, including peri-operative infection, graft thrombosis, and pancreatitis. To overcome the need for major surgery and its associated risks, transplantation of islet cells isolated from human cadaveric pancreata has been developed as an alternative therapeutic approach. In this article, we will provide an overview of clinical islet transplantation (IT) and its advances in the last few years. History of Islet Transplantation Paul Langerhans first described islets of Langerhans within the pancreas in 1869. 11 In 1893, Williams reported the first attempt at IT, 12 in which minced sheep’s pancreas was transplanted into the subcutaneous tissue of a young boy with diabetic ketoacidosis. The boy died 3 days later. The discovery of insulin in 1922 greatly improved glucose control in patients with T1DM, but the inconvenience arising from multiple daily insulin injections, frequent blood sugar measurements, hypoglycemia, and the development of diabetes complications renewed the interest in beta cell- replacement therapy. Touch ME d ica l ME d ia