Changes of Regulatory T Cells and of Proinflammatory and Immunosuppressive Cytokines in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Abstract

Objective. The aim of this study was to investigate the changes of regulatory T cells (Treg), interleukin-6 (IL-6), IL-10, transforming growth factor- β (TGF- β), and tumor necrosis factor-alpha (TNF- α) in patients with type 2 diabetes mellitus (T2DM). Methods. We performed a comprehensive search up to July 2016 for all clinical studies about the changes of Treg, IL-6, IL-10, IL-17, TGF- β, and TNF- α in T2DM patients versus healthy controls. Results. A total of 91 articles (5642 cases and 7378 controls) were included for this meta-analysis. Compared with the controls (all p < 0.001), the patients had increased serum levels of IL-6, TGF- β, and TNF- α but decreased the percentage of peripheral CD4 ⁺CD25 ⁺Foxp3 ⁺Treg and serum IL-10 level. Furthermore, the percentage of peripheral CD4 ⁺CD25 ⁺Foxp3 ⁺Treg ( p < 0.001) and serum IL-10 level ( p = 0.033) were significantly lower in the patients with complication and in the patients without complication, respectively. No significant changes about the percentage of CD4 ⁺CD25 ⁺Treg ( p = 0.360) and serum IL-17 level ( p = 0.459) were found in T2DM patients. Conclusions. T2DM patients have decreased the percentage of peripheral CD4 ⁺CD25 ⁺Foxp3 ⁺Treg and levels of serum IL-10 but elevated serum levels of IL-6, TGF- β, and TNF- α. Presence of diabetic complications further lowers the peripheral CD4 ⁺CD25 ⁺Foxp3 ⁺Treg number.