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

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

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

The study was based on ambulatory care.

Participants included nondiabetic, obese subjects with the metabolic syndrome.

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

Insulin sensitivity as measured by euglycemic hyperinsulinemic clamp.

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 (r² = 0.46, P = 0.01). The disposition index increased significantly after anakinra treatment (P = 0.04), reflecting an improvement in β-cell function.

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