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J Clin Endocrinol Metab. 2011 Jul;96(7):2119-26. doi: 10.1210/jc.2010-2992. Epub 2011 Apr 20.

Treatment with Anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: a randomized, double-blind, placebo-controlled study.

Author information

1
Department of Internal Medicine, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands. e.vanasseldonk@aig.umcn.nl

Abstract

CONTEXT:

Obesity induces low-grade inflammation that may promote the development of insulin resistance. IL-1 is one of the key inflammatory factors.

OBJECTIVE:

The objective of the study was to demonstrate improvement of insulin sensitivity by blocking IL-1.

DESIGN:

This was a randomized, double-blind, crossover study.

SETTING:

The study was based on ambulatory care.

PARTICIPANTS:

Participants included nondiabetic, obese subjects with the metabolic syndrome.

INTERVENTION:

Intervention included 150 mg anakinra sc once daily or matching placebo for 4 wk.

MAIN OUTCOME MEASURE:

Insulin sensitivity as measured by euglycemic hyperinsulinemic clamp.

RESULTS:

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.

CONCLUSIONS:

Our results suggest that anakinra does not improve insulin sensitivity in obese, insulin-resistant, nondiabetic subjects.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00928876.

PMID:
21508140
DOI:
10.1210/jc.2010-2992
[Indexed for MEDLINE]

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