OBJECTIVETo describe trends of primary efficacy and safety outcomes of islet transplantation in type 1 diabetes recipients with severe hypoglycemia from the Collaborative Islet Transplant Registry (CITR) from 1999 to 2010.RESEARCH DESIGN AND METHODSA total of 677 islet transplant-alone or islet-after-kidney recipients with type 1 diabetes in the CITR were analyzed for five primary efficacy outcomes and overall safety to identify any differences by early (1999–2002), mid (2003–2006), or recent (2007–2010) transplant era based on annual follow-up to 5 years.RESULTSInsulin independence at 3 years after transplant improved from 27% in the early era (1999–2002, n = 214) to 37% in the mid (2003–2006, n = 255) and to 44% in the most recent era (2007–2010, n = 208; P = 0.006 for years-by-era; P = 0.01 for era alone). C-peptide ≥0.3 ng/mL, indicative of islet graft function, was retained longer in the most recent era (P < 0.001). Reduction of HbA1c and resolution of severe hypoglycemia exhibited enduring long-term effects. Fasting blood glucose stabilization also showed improvements in the most recent era. There were also modest reductions in the occurrence of adverse events. The islet reinfusion rate was lower: 48% by 1 year in 2007–2010 vs. 60–65% in 1999–2006 (P < 0.01). Recipients that ever achieved insulin-independence experienced longer duration of islet graft function (P < 0.001).CONCLUSIONSThe CITR shows improvement in primary efficacy and safety outcomes of islet transplantation in recipients who received transplants in 2007–2010 compared with those in 1999–2006, with fewer islet infusions and adverse events per recipient.

No abstract

Streptozotocin (STZ)-induced diabetes mellitus (DM) offers a very cost effective and expeditious technique that can be used in most strains of rodents, opening the field of DM research to an array of genotypic and phenotypic options that would otherwise be inaccessible. Despite widespread use of STZ in small animal models, the data available concerning drug preparation, dosing and administration, time to onset and severity of DM, and any resulting moribundity and mortality are often limited and inconsistent. Because of this, investigators inexperienced with STZ-induced diabetes may find it difficult to precisely design new studies with this potentially toxic chemical and account for the severity of DM it is capable of inducing. Until a better option becomes available, attempts need to be made to address shortcomings with current STZ-induced DM models. In this paper we review the literature and provide data from our pancreatic islet transplantation experiments using single high dose STZ-induced DM in NCr Athymic Nude mice with hopes of providing clarification for study design, suggesting refinements to the process, and developing a more humane process of chemical diabetes induction.

OBJECTIVE -To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS -We searched databases (MEDLINE, EM-BASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence.RESULTS -Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (Ͻ10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P ϭ 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted.CONCLUSIONS -Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs. Diabetes Care 25:583-592, 2002P osttransplantation diabetes (PTD) is a complication of solid-organ transplantation. Beyond the description of PTD as the development of diabetes after transplantation, there is no consensus regarding the definition of this condition. Estimates of the frequency of PTD range from 2 to 50%. Some factors, such as age of the transplant recipient, are consistently described as increasing the risk of PTD. Under dispute is the importance of other factors, such as the recipients ethnicity, body weight, immunosuppressive regimen, and family history of diabetes, as well as the vital status of the organ donor. The prognostic implications of PTD and its optimal treatment are similarly unclear.The goals of this systematic review were to estimate the incidence of PTD, identify the risk factors for its development, determine its implications for prognosis, and discover treatment strategies that lead to improved patient outcomes. RESEARCH DESIGN AND METHODS Questions askedOur review was designed to answer four questions: 1) For patients with no history of diabetes before transplantation, what is the risk that PTD will develop? 2) What are the risk factors for the development of PTD? 3) What is the prognosis for patients with PTD? 4) Which therapies improve glycemic control and prognosis in patients with PTD? Identification and retrieval of primary studiesWe searched MEDLINE (O...