Interleukin-1-receptor antagonist in type 2 diabetes mellitus. Export

@article{citeulike:2842920, abstract = {BACKGROUND: The expression of interleukin-1-receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1beta in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell proliferation, and apoptosis. METHODS: In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1-receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive placebo. At baseline and at 13 weeks, all patients underwent an oral glucose-tolerance test, followed by an intravenous bolus of 0.3 g of glucose per kilogram of body weight, 0.5 mg of glucagon, and 5 g of arginine. In addition, 35 patients underwent a hyperinsulinemic-euglycemic clamp study. The primary end point was a change in the level of glycated hemoglobin, and secondary end points were changes in beta-cell function, insulin sensitivity, and inflammatory markers. RESULTS: At 13 weeks, in the anakinra group, the glycated hemoglobin level was 0.46 percentage point lower than in the placebo group (P=0.03); C-peptide secretion was enhanced (P=0.05), and there were reductions in the ratio of proinsulin to insulin (P=0.005) and in levels of interleukin-6 (P<0.001) and C-reactive protein (P=0.002). Insulin resistance, insulin-regulated gene expression in skeletal muscle, serum adipokine levels, and the body-mass index were similar in the two study groups. Symptomatic hypoglycemia was not observed, and there were no apparent drug-related serious adverse events. CONCLUSIONS: The blockade of interleukin-1 with anakinra improved glycemia and beta-cell secretory function and reduced markers of systemic inflammation. (ClinicalTrials.gov number, NCT00303394 [ClinicalTrials.gov].).}, address = {Steno Diabetes Center, Gentofte, Denmark.}, author = {Larsen, C. M. and Faulenbach, M. and Vaag, A. and V{\o}lund, A. and Ehses, J. A. and Seifert, B. and Mandrup-Poulsen, T. and Donath, M. Y.}, citeulike-article-id = {2842920}, citeulike-linkout-0 = {http://dx.doi.org/10.1056/NEJMoa065213}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17429083}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17429083}, day = {12}, doi = {10.1056/NEJMoa065213}, issn = {1533-4406}, journal = {The New England journal of medicine}, keywords = {anakinra}, month = {April}, number = {15}, pages = {1517--1526}, posted-at = {2008-07-20 03:37:33}, priority = {2}, title = {Interleukin-1-receptor antagonist in type 2 diabetes mellitus.}, url = {http://dx.doi.org/10.1056/NEJMoa065213}, volume = {356}, year = {2007} }

TY - JOUR ID - citeulike:2842920 L3 - citeulike-article-id:2842920 N2 - BACKGROUND: The expression of interleukin-1-receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1beta in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell proliferation, and apoptosis. METHODS: In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1-receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive placebo. At baseline and at 13 weeks, all patients underwent an oral glucose-tolerance test, followed by an intravenous bolus of 0.3 g of glucose per kilogram of body weight, 0.5 mg of glucagon, and 5 g of arginine. In addition, 35 patients underwent a hyperinsulinemic-euglycemic clamp study. The primary end point was a change in the level of glycated hemoglobin, and secondary end points were changes in beta-cell function, insulin sensitivity, and inflammatory markers. RESULTS: At 13 weeks, in the anakinra group, the glycated hemoglobin level was 0.46 percentage point lower than in the placebo group (P=0.03); C-peptide secretion was enhanced (P=0.05), and there were reductions in the ratio of proinsulin to insulin (P=0.005) and in levels of interleukin-6 (P<0.001) and C-reactive protein (P=0.002). Insulin resistance, insulin-regulated gene expression in skeletal muscle, serum adipokine levels, and the body-mass index were similar in the two study groups. Symptomatic hypoglycemia was not observed, and there were no apparent drug-related serious adverse events. CONCLUSIONS: The blockade of interleukin-1 with anakinra improved glycemia and beta-cell secretory function and reduced markers of systemic inflammation. (ClinicalTrials.gov number, NCT00303394 [ClinicalTrials.gov].). IS - 15 JF - The New England journal of medicine SN - 1533-4406 AD - Steno Diabetes Center, Gentofte, Denmark. EP - 1526 TI - Interleukin-1-receptor antagonist in type 2 diabetes mellitus. VL - 356 SP - 1517 KW - anakinra AU - Larsen, CM AU - Faulenbach, M AU - Vaag, A AU - Vølund, A AU - Ehses, JA AU - Seifert, B AU - Mandrup-Poulsen, T AU - Donath, MY PY - 2007/04/12/ UR - http://dx.doi.org/10.1056/NEJMoa065213 ER -