A systematic review and meta-analysis on the regulation of programmed cell death-1 on T-cells in type 2 diabetes

BACKGROUND: To assess T-cell exhaustion mediated by programmed cell death 1 (PD-1) pathway in patients living with type 2 diabetes (T2D). METHODS: MEDLINE and ProQuest electronic databases were searched for eligible studies from inception up to February 2020. The risk of bias and the quality of evidence were independently assessed by two reviewers using the modified Newcastle-Ottawa Scale adapted for cross-sectional studies and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool, respectively. The random effects model was used to calculate effect estimates. RESULTS: We identified 5 studies involving 380 participants which met the inclusion criteria. The pooled estimates showed elevated T helper cell exhaustion in patients with T2D in comparison to controls (mean difference [MD]: 2.57% [95% confidence interval [CI]: –3.84, 8.97]; I(2) = 100%, P < .00001). Likewise, T2D patients had increased levels of cytotoxic T-cells exhaustion (MD: 3.09% [95% CI: –12.96, 19.14]; I(2) = 100%, P < .00001). Although the upregulation of PD-1 on T-cells did not affect glucose metabolism-related profiles, it was associated with inflammation and the development of cardiovascular disease. CONCLUSION: In patients living with T2D, immune dysfunction is at least in part due to T-cell exhaustion mediated by the upregulation of PD-1 expression. Therefore, the use of immune checkpoint inhibitors as a therapeutic strategy may be beneficial in restoring immune function in patients with T2D.