The association between interleukin family and diabetes mellitus and its complications: An overview of systematic reviews and meta-analyses

To evaluate and summarize the association between interleukin (IL) concentrations and diabetes mellitus (DM) and its complications.Meta-analyses and eligible individual studies of observational studies investigating the associations between IL and DM and its complications were included. The random-effects model was used to estimate the summary effect, and the heterogeneity among studies was assessed using the Q-statistic and the I2 metric; The Egger's regression and the χ2 test were used to test for small study effects and excess significance bias.This overview identified 34 meta-analyses that investigated the association between IL concentrations and DM and its complications. Meta-analyses of prospective studies indicated that elevated circulating IL-6 and IL-1β had predictive value for the incident of type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM) as well as gestational diabetes mellitus (GDM), and the overall Hazard Ratio (HR) of T2DM was 1.28 (95 % CI: 1.17, 1.40; P＜0.001) per 1 log pg/ml increment in IL-6 levels, however, there was no correlation between circulating IL-10 levels and DM. Meanwhile, the increased level of IL-6 was significantly associated several diabetic complications (Diabetic kidney disease[DKD], diabetic peripheral neuropathy[DPN], and cognitive impairment[CI]), and for the diabetic retinopathy (DR), the levels of IL-1β, IL-8 and IL-10 in the aqueous humor and vitreous humor, but not the blood were significantly correlated with it.Multiple ILs, such as the IL-6 and IL-1β, are definitively linked to DM and its complications, and they may be new targets for the diagnosis and treatment, but stronger evidence needs to be confirmed by prospective studies with larger sample sizes and longer observation periods.