Association of Cyclic RNAs with the Risk of Type 2 Diabetes Mellitus in Han Chinese

Abstract

Background The prevalence of diabetes is increasing year-on-year. However, current diagnostic methods have many deficiencies in early identification of type 2 diabetes mellitus (T2DM) . Epigenetic factors may be associated with the development and secretory function of pancreatic islet β cells, which reduces the sensitivity of the body to the effects of insulin, ultimately leading to the development of T2DM. Objective To identify differentially expressed hsa_circ_0005414, hsa_circ_0139634, hsa_circ_0032491 and hsa_circ_0002922 in the peripheral blood of Han Chinese patients with T2DM to assess the clinical significance, and to explore the relationship between candidate circRNAs and T2DM in Han Chinese. Methods From the Department of Endocrinology and Metabolism, the First Affiliated Hospital of Shihezi University School of Medicine between September 2020 and June 2021, 21 Han Chinese patients with T2DM were selected. 22 healthy examinees were also selected as controls. Glucose metabolism indices and expression levels (2-ΔΔCT) of the four candidate circRNAs were measured. The relationship between expression levels of candidate circRNAs and glucose metabolism indices was explored using multiple linear regression analysis. Univariate Logistic regression analysis was used to explore the correlation of expression levels of candidate circRNAs with the risk of T2DM. Receiver operating characteristic (ROC) curve analysis was used to assess diagnostic values of these candidate circRNAs for T2DM. Results T2DM patients had higher relative expression levels of hsa_circ_0032491 and hsa_circ_0002922, and lower relative expression levels of hsa_circ_0005414 and hsa_circ_0139634 than did the controls (P<0.05) . Multiple linear regression analysis showed that fasting plasma glucose and Log2-transformed fasting insulin were associated with the expression level of hsa_circ_0032491 in Chinese Han with T2DM (P<0.05) , with an R2=0.503. The areas under the ROC curves of hsa_circ_0005414, hsa_circ_0139634, hsa_circ_0032491, and hsa_circ_0002922 for the diagnosis of T2DM in Chinese Han were 0, 0.199, 0.968, and 0.844, respectively. Univariate Logistic regression analysis showed that elevated relative expression levels of hsa_circ_0139634 may be associated with reduced risk of T2DM 〔OR=0.092, 95%CI (0.016, 0.520) , P=0.007〕, while elevated relative expression levels of hsa_circ_0032491〔OR=3.607, 95%CI (1.625, 8.004) , P=0.002〕 and hsa_circ_0002922〔OR=5.105, 95%CI (1.683, 15.482) , P=0.004〕 may be associated with increased risk of T2DM. Conclusion hsa_circ_0032491 and hsa_circ_0002922 could be used as biomarkers for T2DM in Han Chinese. hsa_circ_0139634, hsa_circ_0032491 and hsa_circ_0002922 could be independent predictors of T2DM in Han Chinese population. An increase in the relative expression level of hsa_circ_0139634 decreased the risk of T2DM, while an increase in the relative expression levels of hsa_circ_0032491 and hsa_circ_0002922 increased the risk of T2DM, suggesting that these three candidate circRNAs may play an important role in the development of T2DM.

Keywords

• diabetes mellitus, type 2|rna, circular|epigenomics|risk factors|biomarkers|han nationality|diagnosis|forecasting