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Interleukin-1-receptor antagonist in type 2 diabetes mellitus

Larsen, Claus M.; Faulenbach, Mirjam; Vaag, Allan LU ; Volund, Aage; Ehses, Jan A.; Seifert, Burkhardt; Mandrup-Poulsen, Thomas and Donath, Marc Y. (2007) In New England Journal of Medicine 356(15). p.1517-1526
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-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... (More)
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<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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
New England Journal of Medicine
volume
356
issue
15
pages
1517 - 1526
publisher
Massachusetts Medical Society
external identifiers
  • wos:000245624400005
  • scopus:34247170807
ISSN
0028-4793
DOI
10.1056/NEJMoa065213
language
English
LU publication?
yes
id
4719f301-4b68-41b5-a9e0-2fb471944e6a (old id 670019)
date added to LUP
2007-12-12 12:57:22
date last changed
2017-11-19 03:32:49
@article{4719f301-4b68-41b5-a9e0-2fb471944e6a,
  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-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&lt;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.},
  author       = {Larsen, Claus M. and Faulenbach, Mirjam and Vaag, Allan and Volund, Aage and Ehses, Jan A. and Seifert, Burkhardt and Mandrup-Poulsen, Thomas and Donath, Marc Y.},
  issn         = {0028-4793},
  language     = {eng},
  number       = {15},
  pages        = {1517--1526},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {Interleukin-1-receptor antagonist in type 2 diabetes mellitus},
  url          = {http://dx.doi.org/10.1056/NEJMoa065213},
  volume       = {356},
  year         = {2007},
}