Interleukin-1-receptor antagonist in type 2 diabetes mellitus
(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:
https://lup.lub.lu.se/record/670019
- author
- Larsen, Claus M. ; Faulenbach, Mirjam ; Vaag, Allan LU ; Volund, Aage ; Ehses, Jan A. ; Seifert, Burkhardt ; Mandrup-Poulsen, Thomas and Donath, Marc Y.
- organization
- publishing date
- 2007
- 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
- 2016-04-01 12:06:02
- date last changed
- 2024-04-08 23:52:18
@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<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}},
doi = {{10.1056/NEJMoa065213}},
volume = {{356}},
year = {{2007}},
}