Chemokines in Type 1 Diabetes Mellitus

BACKGROUND: Previous studies suggested that chemokines may play an important role in the formation and mediation of immune microenvironments of patients affected by Type 1 Diabetes Mellitus (T1DM). The aim of this study was to summarise available evidence on the associations of different chemokines with T1DM. METHODS: Following PRISMA guidelines, we systematically searched in PubMed, Web of Science, Embase and Cochrane Library databases for studies on the associations of different chemokines with T1DM. The effect size of the associations were the standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) of the chemokines concentrations, calculated as group differences between the T1DM patients and the controls. These were summarized using network meta-analysis, which was also used to rank the chemokines by surface under cumulative ranking curve (SUCRA) probabilities. RESULTS: A total of 32 original studies on the association of different chemokines with T1DM were identified. Fifteen different chemokine nodes were compared between 15,683 T1DM patients and 15,128 controls, and 6 different chemokine receptor nodes were compared between 463 T1DM patients and 460 controls. Circulating samples (blood, serum, and plasma) showed that concentrations of CCL5 and CXCL1 were significantly higher in the T1DM patients than in the controls (SMD of 3.13 and 1.50, respectively). On the other hand, no significant difference in chemokine receptors between T1DM and controls was observed. SUCRA probabilities showed that circulating CCL5 had the highest rank in T1DM among all the chemokines investigated. CONCLUSION: The results suggest that circulating CCL5 and CXCL1 may be promising novel biomarkers of T1DM. Future research should attempt to replicate these findings in longitudinal studies and explore potential mechanisms underlying this association.