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.

Leflunomide inhibits Polyoma virus replication in vitro and closely monitored leflunomide therapy with specifically targeted blood levels appears to be a safe and effective treatment for Polyoma BK nephropathy.

tients in the half-life of A77 1726, the known risk of toxic effects on the liver, and the requirement for doses that exceed recommendations for rheumatoid arthritis, this therapy should be monitored by fre-quent analysis of blood levels of the active metabolite and liver enzymes.

Diabetes remains a devastating disease, with tremendous cost in terms of human suffering and healthcare expenditures. A bioartificial pancreas has the potential as a promising approach to preventing or reversing complications associated with this disease. Bioartificial pancreatic constructs are based on encapsulation of islet cells with a semipermeable membrane so that cells can be protected from the host's immune system. Encapsulation of islet cells eliminates the requirement of immunosuppressive drugs, and offers a possible solution to the shortage of donors as it may allow the use of animal islets or insulin-producing cells engineered from stem cells. During the past 2 decades, several major approaches for immunoprotection of islets have been studied. The microencapsulation approach is quite promising because of its improved diffusion capacity, and technical ease of transplantation. It has the potential for providing an effective long-term treatment or cure of Type 1 diabetes.

The purpose of the present study was to examine the role played by structural differences among fatty acids in their effect on insulin secretion by isolated perifused murine islets. Insulin secretion measured by radioimmunoassay was assessed either as total insulin output (ng.6 islets-1.20 min-1) or as percent of basal insulin secretion. Raising the glucose concentration from a basal 5.5 to 27.7 mM caused an increase of insulin output from 6.69 +/- 1.59 to 19.92 +/- 4.99 ng.6 islets-1.20 min-1 (P < 0.05) in control (untreated) islets. However, after 20-min exposure of islets to 5 mM 16:0 or 18:2, the effect of 27.7 mM glucose was enhanced or diminished, respectively. Basal insulin output (100% basal) changed to 44 +/- 10% basal (P < 0.005) with the addition of 5 mM 4:0 but was not altered when 4:0 was replaced by 6:0. Insulin output increased modestly with 5 mM 8:0 but significantly (P < 0.05) with 10:0 until a maximal of 280 +/- 24% basal with 12:0 (P < 0.01), then fell to 110 +/- 18 and 93 +/- 15% basal (P < 0.05) with 14:0 and 16:0, respectively. The addition of 5 mM 18:0 inhibited insulin secretion to 30 +/- 10% of basal (P < 0.003), and this effect was not caused by fatty acid interference with insulin assay.(ABSTRACT TRUNCATED AT 250 WORDS)