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

Randomized Controlled Trial

. 2011 Jul;96(7):2119-26.

doi: 10.1210/jc.2010-2992. Epub 2011 Apr 20.

Affiliations

PMID: 21508140
DOI: 10.1210/jc.2010-2992

Free article

Randomized Controlled Trial

Edwin J P van Asseldonk et al. J Clin Endocrinol Metab. 2011 Jul.

Free article

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.

PubMed Disclaimer

Cited by

Is there a role for the adaptive immune system in pancreatic beta cell failure in type 2 diabetes?
Westwell-Roper C, Ehses JA. Westwell-Roper C, et al. Diabetologia. 2014 Mar;57(3):447-50. doi: 10.1007/s00125-013-3151-2. Epub 2013 Dec 21. Diabetologia. 2014. PMID: 24362729
Interferon-gamma released from omental adipose tissue of insulin-resistant humans alters adipocyte phenotype and impairs response to insulin and adiponectin release.
Wentworth JM, Zhang JG, Bandala-Sanchez E, Naselli G, Liu R, Ritchie M, Smyth GK, O'Brien PE, Harrison LC. Wentworth JM, et al. Int J Obes (Lond). 2017 Dec;41(12):1782-1789. doi: 10.1038/ijo.2017.180. Epub 2017 Aug 3. Int J Obes (Lond). 2017. PMID: 28769120
Effects of colchicine in adults with metabolic syndrome: A pilot randomized controlled trial.
Demidowich AP, Levine JA, Onyekaba GI, Khan SM, Chen KY, Brady SM, Broadney MM, Yanovski JA. Demidowich AP, et al. Diabetes Obes Metab. 2019 Jul;21(7):1642-1651. doi: 10.1111/dom.13702. Epub 2019 Apr 2. Diabetes Obes Metab. 2019. PMID: 30869182 Free PMC article. Clinical Trial.
How biologics targeting the IL-1 system are being considered for the treatment of type 2 diabetes.
Böni-Schnetzler M, Donath MY. Böni-Schnetzler M, et al. Br J Clin Pharmacol. 2013 Aug;76(2):263-8. doi: 10.1111/j.1365-2125.2012.04297.x. Br J Clin Pharmacol. 2013. PMID: 22506644 Free PMC article. Review.

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