Effects of thiazolidinedione therapy on inflammatory markers of type 2 diabetes: a meta-analysis of randomized controlled trials

Abstract

Background: Inflammation is a common feature in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to assess the influence of thiazolidinedione (TZD) therapy on the circulating levels of inflammatory markers in patients with T2DM.

Methods and results: We searched the databases Medline, Embase, ScienceDirect, Web of Science, SpringerLink, and the Cochrane Library for randomized controlled trials (RCTs) that examined the effects of thiazolidinedione vs. a placebo on patients with T2DM. The main outcomes were absolute changes in levels of circulating inflammatory markers. Twenty-seven RCTs were included and data were analyzed using a fixed-effect model or a random-effect model based on heterogeneity. Pooled results indicated that circulating levels of high-sensitivity C reactive protein (hsCRP; SMD = -0.65, 95% CI = -0.98 to -0.32, p < 0.01), monocyte chemoattractant protein-1 (MCP-1; WMD = -54.19, 95% CI = -73.86 to -34.52, p < 0.01), von Willebrand factor% (vWF%; WMD = -8.18, 95% CI = -13.54 to -2.81, p 0.01), fibrinogen (SMD = -0.26, 95% CI = -0.41 to -0.11, p < 0.01) and E-selectin(WMD = -3.57, 95% CI = -5.59 to -1.54, p <0.01) were significantly decreased after TZD therapy. However, interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand, plasminogen activator inhibitor 1 (PAI-1) and intercellular adhesion molecule (ICAM-1) were not significantly affected. Subgroup analyses of PAI-1, vWF% and fibrinogen in terms of trial drugs showed significant reductions for rosiglitazone (all p valuses< 0.05), but not pioglitazone treatment. Conversely, the E-selectin (p < 0.01) lowering effect only existed in the pioglitazone group. Further, rosiglitazone and pioglitazone treatment reduced serum hsCRP and MCP-1 but had no marked effects on MMP-9, IL-6 and ICAM-1.

Conclusions: Limited evidence suggested that TZD therapy had anti-inflammatory property that might contribute to its beneficial effect on inflammatory state in patients with type 2 diabetes.

Fig 1. Process of study selection.

Fig 2. Forest plots from meta-analysis of RCTs regarding the role of thiazolidinedinediones therapy in plasma concentrations of pro-inflammatory markers hsCRP(A), IL-6(B), MMP-9(C), sCD40L(D) and MCP-1(E).

Fig 3. Forest plots from meta-analysis of RCTs regarding the role of thiazolidinedinediones therapy in plasma concentrations of pro-thrombotic markers, vWF%(A), PAI-1(B)and fibrinogen(C).

Fig 4. Forest plots from meta-analysis of RCTs regarding the role of thiazolidinedinediones therapy in plasma concentrations of adhesion molecules, E-selectin(A) and ICAM-1(B).