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Sustained Effects of Interleukin-1 Receptor Antagonist Treatment in Type 2 Diabetes

Larsen, Claus M.; Faulenbach, Mirjam; Vaag, Allan LU ; Ehses, Jan A.; Donath, Marc Y. and Mandrup-Poulsen, Thomas (2009) In Diabetes Care 32(9). p.1663-1668
Abstract
OBJECTIVE - Interleukin (IL)-1 impairs insulin secretion and induces P-cell apoptosis. Pancreatic beta-cell IL-1 expression is increased and interleukin-1 receptor antagonist (IL-1Ra) expression reduced in patients with type 2 diabetes. Treatment with recombinant IL-1Ra improves glycemia and P-cell function and reduces inflammatory markers in patients with type 2 diabetes. Here we investigated the durability of these responses. RESEARCH DESIGN AND METHODS - Among 70 ambulatory patients who had type 2 diabetes, A1C >7.5%, and BMI >27 kg/m(2) and were randomly assigned to receive 13 weeks of anakinra, a recombinant human IL-1Ra, or placebo, 67 completed treatment and were included in this double-blind 39-week follow-up study. Primary... (More)
OBJECTIVE - Interleukin (IL)-1 impairs insulin secretion and induces P-cell apoptosis. Pancreatic beta-cell IL-1 expression is increased and interleukin-1 receptor antagonist (IL-1Ra) expression reduced in patients with type 2 diabetes. Treatment with recombinant IL-1Ra improves glycemia and P-cell function and reduces inflammatory markers in patients with type 2 diabetes. Here we investigated the durability of these responses. RESEARCH DESIGN AND METHODS - Among 70 ambulatory patients who had type 2 diabetes, A1C >7.5%, and BMI >27 kg/m(2) and were randomly assigned to receive 13 weeks of anakinra, a recombinant human IL-1Ra, or placebo, 67 completed treatment and were included in this double-blind 39-week follow-up study. Primary outcome was change in P-cell function after anakinra withdrawal. Analysis was done by intention to treat. RESULTS - Thirty-nine weeks after anakinra withdrawal, the proinsulin-to-insulin (PI/I) ratio but not stimulated C-peptide remained improved (by -0.07 [95% CI -0.14 to -0.02], P = 0.011) compared with values in placebo-treated patients. Interestingly, a subgroup characterized by genetically determined low baseline IL-1Ra serum levels maintained the improved stimulated C-peptide obtained by 13 weeks of IL-1Ra treatment. Reductions in C-reactive protein (-3.2 mg/l [-6.2 to -1.1], P = 0.014) and in IL-6 (-1.4 mg/l [-2.6 to -0.3], P = 0.036) were maintained until the end of study. CONCLUSIONS - IL-1 blockade with anakinra induces improvement of the PIA ratio and markers of systemic inflammation lasting 39 weeks after treatment withdrawal. (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
Diabetes Care
volume
32
issue
9
pages
1663 - 1668
publisher
American Diabetes Association
external identifiers
  • wos:000269687100019
  • scopus:69549105888
ISSN
1935-5548
DOI
10.2337/dc09-0533
language
English
LU publication?
yes
id
b214e85e-56b3-41d4-ba9f-1b3eb362c2ee (old id 1492395)
date added to LUP
2009-10-16 15:48:01
date last changed
2017-11-12 03:46:21
@article{b214e85e-56b3-41d4-ba9f-1b3eb362c2ee,
  abstract     = {OBJECTIVE - Interleukin (IL)-1 impairs insulin secretion and induces P-cell apoptosis. Pancreatic beta-cell IL-1 expression is increased and interleukin-1 receptor antagonist (IL-1Ra) expression reduced in patients with type 2 diabetes. Treatment with recombinant IL-1Ra improves glycemia and P-cell function and reduces inflammatory markers in patients with type 2 diabetes. Here we investigated the durability of these responses. RESEARCH DESIGN AND METHODS - Among 70 ambulatory patients who had type 2 diabetes, A1C >7.5%, and BMI >27 kg/m(2) and were randomly assigned to receive 13 weeks of anakinra, a recombinant human IL-1Ra, or placebo, 67 completed treatment and were included in this double-blind 39-week follow-up study. Primary outcome was change in P-cell function after anakinra withdrawal. Analysis was done by intention to treat. RESULTS - Thirty-nine weeks after anakinra withdrawal, the proinsulin-to-insulin (PI/I) ratio but not stimulated C-peptide remained improved (by -0.07 [95% CI -0.14 to -0.02], P = 0.011) compared with values in placebo-treated patients. Interestingly, a subgroup characterized by genetically determined low baseline IL-1Ra serum levels maintained the improved stimulated C-peptide obtained by 13 weeks of IL-1Ra treatment. Reductions in C-reactive protein (-3.2 mg/l [-6.2 to -1.1], P = 0.014) and in IL-6 (-1.4 mg/l [-2.6 to -0.3], P = 0.036) were maintained until the end of study. CONCLUSIONS - IL-1 blockade with anakinra induces improvement of the PIA ratio and markers of systemic inflammation lasting 39 weeks after treatment withdrawal.},
  author       = {Larsen, Claus M. and Faulenbach, Mirjam and Vaag, Allan and Ehses, Jan A. and Donath, Marc Y. and Mandrup-Poulsen, Thomas},
  issn         = {1935-5548},
  language     = {eng},
  number       = {9},
  pages        = {1663--1668},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {Sustained Effects of Interleukin-1 Receptor Antagonist Treatment in Type 2 Diabetes},
  url          = {http://dx.doi.org/10.2337/dc09-0533},
  volume       = {32},
  year         = {2009},
}