Circulating miR-335-5p can be a potential biomarker for diabetes: a population-based nested case-control study

To investigate the association between miR-335-5p and diabetes mellitus, and to analyze the mediating role of inflammatory factors, including IL-6 and NLRP3 protein level. A case-control study with 180 participants was firstly carried out, then a nested case-control study was subsequently performed. Multivariate logistic regression and conditional logistic regressions were used to analyze the relationship between miR-335-5p and diabetes. Delong test was used to compare the area under the curve (AUC) before and after adding miR-335-5p to the traditional diabetes prediction models. Mediation analysis was used to demonstrate the potential mediators between miR-335-5p and diabetes. The log2-transformed expression level of miR-335-5p was higher in diagnosed diabetes (OR = 1.64, P = 0.013); while the baseline level of miR-335-5p was lower in the new incident diabetic patients (OR = 0.26, P = 0.002). The AUC significantly increased after adding baseline miR-335-5p to the Framingham Diabetes Risk Model (FDRM) and New Chinese Diabetes Risk Score (NCDRS) model ( P FDRM = 0.010 and P NCDRS = 0.023). In addition, NLRP3 protein level mediated 42.50% of the association between miR-335-5p and the pathogenesis of diabetes ( P = 0.012). Circulating miR-335-5p is associated with diabetes, but this relationship may be modulated by age, disease duration, and disease status, and partially mediated by NLRP3. The CoHort study on CHronic disease of Community Natural population in Beijing-Tianjin-Hebei region (CHCN-BTH) had been registered in Chinese Clinical Trial Register (ChiCTR, https://www.chictr.org.cn/index.html ) on July 25th 2019. The clinical trial number was ChiCTR1900024725.