Interleukin-1-receptor antagonist in type 2 diabetes mellitus
Interleukin-1-receptor antagonist in type 2 diabetes mellitus
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DOI：
10.1056/nejmoa065213
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发表时间：
2007-04-12
影响因子：
158.5
通讯作者：
Donath, Marc Y.
中科院分区：
文献类型：
--
作者：
Larsen, Claus M.;Faulenbach, Mirjam;Donath, Marc Y.
背景：2型糖尿病患者胰岛白介素1受体拮抗剂的表达减少，高糖浓度诱导人胰岛β细胞产生白介素1，导致胰岛素分泌受损，细胞增殖减少，细胞凋亡。方法：在这项涉及70例2型糖尿病患者的双盲平行试验中，我们随机分配34例患者接受阿纳金纳100 mg(一种重组人白介素1受体拮抗剂)皮下注射，连续13周，36例患者接受安慰剂治疗。在基线和13周时，所有患者都接受了口服葡萄糖耐量试验，然后静脉推注每公斤体重0.3克葡萄糖、0.5毫克胰高血糖素和5克精氨酸。此外，35名患者接受了高胰岛素-正常血糖钳夹研究。结果：13周时，Anakinra组糖化血红蛋白水平比安慰剂组低0.46个百分点(P=0.0 3)，C肽分泌增加(P=0.0 5)，胰岛素原/胰岛素比值(P=0.005.0 5)和IL-6水平降低(P=0.0 5)。
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-1(beta) 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