Department of Internal Medicine, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.
J Clin Endocrinol Metab. 2011 Jul;96(7):2119-26. doi: 10.1210/jc.2010-2992. Epub 2011 Apr 20.
Obesity induces low-grade inflammation that may promote the development of insulin resistance. IL-1 is one of the key inflammatory factors.
The objective of the study was to demonstrate improvement of insulin sensitivity by blocking IL-1.
This was a randomized, double-blind, crossover study.
The study was based on ambulatory care.
Participants included nondiabetic, obese subjects with the metabolic syndrome.
Intervention included 150 mg anakinra sc once daily or matching placebo for 4 wk.
Insulin sensitivity as measured by euglycemic hyperinsulinemic clamp.
A total of 13 of 19 subjects completed the study. Although anakinra treatment resulted in a significantly lower level of inflammation illustrated by a reduction in circulating C-reactive protein concentrations and leukocyte numbers, insulin sensitivity was not significantly different after anakinra treatment (2.8 × 10(-2) ± 0.5 × 10(-2)) compared with placebo treatment (2.4 × 10(-2) ± 0.3 × 10(-2) μmol/kg(-1) · min(-1) · pmol(-1), P = 0.15). Adipose tissue examination, performed to analyze local effects of IL-1 receptor antagonist, showed an increased influx of macrophages after treatment with anakinra most likely due to an injection site reaction caused by the vehicle (0.28 ± 0.05 vs. 0.11 ± 0.01 macrophages per adipocyte, P = 0.005). The differences in individual subject insulin sensitivity after anakinra as compared with placebo between subjects were negatively correlated with macrophage infiltration into the adipose tissue (r(2) = 0.46, P = 0.01). The disposition index increased significantly after anakinra treatment (P = 0.04), reflecting an improvement in β-cell function.
Our results suggest that anakinra does not improve insulin sensitivity in obese, insulin-resistant, nondiabetic subjects.
肥胖会引起低度炎症，从而可能促进胰岛素抵抗的发展。白细胞介素-1（IL-1）是关键的炎症因子之一。
本研究旨在通过阻断白细胞介素-1（IL-1）来证明胰岛素敏感性的改善。
这是一项随机、双盲、交叉研究。
该研究基于门诊护理。
参与者包括患有代谢综合征的非糖尿病肥胖受试者。
干预措施包括每天一次皮下注射 150mg 阿那白滞素或匹配的安慰剂，持续 4 周。
通过正葡萄糖高胰岛素钳夹试验测量的胰岛素敏感性。
19 名受试者中有 13 名完成了研究。尽管阿那白滞素治疗导致循环 C 反应蛋白浓度和白细胞数量降低，炎症水平显著降低，但与安慰剂治疗相比（2.8×10(-2)±0.5×10(-2)μmol/kg(-1)·min(-1)·pmol(-1)），胰岛素敏感性并没有显著差异（2.4×10(-2)±0.3×10(-2)μmol/kg(-1)·min(-1)·pmol(-1)，P=0.15）。为分析白细胞介素-1 受体拮抗剂的局部作用而进行的脂肪组织检查显示，在用阿那白滞素治疗后，巨噬细胞的流入增加，这很可能是由于载体引起的注射部位反应（0.28±0.05与 0.11±0.01 个巨噬细胞/脂肪细胞，P=0.005）。与安慰剂相比，受试者接受阿那白滞素治疗后的个体胰岛素敏感性差异与脂肪组织中巨噬细胞浸润呈负相关（r(2)=0.46，P=0.01）。阿那白滞素治疗后，处置指数显著增加（P=0.04），反映了β细胞功能的改善。
我们的结果表明，在肥胖、胰岛素抵抗的非糖尿病受试者中，阿那白滞素不能改善胰岛素敏感性。
