The Expression Level And Clinical Significance Of Plasmamirna-126in Patients With Type1Diabetes

BackgroundType1diabetes is a chronic inflammatory disease, caused by a selective destruction of the insulin producing β-cells in the islets. The incidence of type1diabetes has consistently increased worldwide during the last decades, especially in children and developed countries. Type1diabetes is associated with the appearance of humoral and cellular islet autoimmunity, and a defective immunoregulation appears to be involved. The exact etiology and pathogenesis of type1diabetes, however, is still unknown.MiRNAs are a family of small, non-coding single-strand RNA molecules of18-25nucleotides (18-25nt) in length, widely expressed in plants and animals, function by partially binding to the3’ untranslated region (UTR) of their target gene transcripts either mediating transcript degradation or translational inhibition, thus regulate gene expression at the post-transcriptional level. Due to the expression of miRNAs generally has tissue specificity or time specificity, they may play an important role of inhibition of gene expression in a particular stage of different biological processes, thus participating in the regulation of a variety of pathophysiological processes. MiRNAs can steadily exist in the circulation and other various kinds of body fluids. What’s more, miRNAs, particularly serum miRNAs, are resistant to RNase digestion. The stability of serum miRNAs was further studied by using sera, from various sources, after treatment under harsh conditions including boiling, low/high pH, extended storage, freeze-thaw cycles, and so on. MiRNAs have been used as biomarkers in tumor, inflammation, cell proliferation and apoptosis, diabetes and cardiovascular diseases and other fields. The present research shows that the expression of miRNA-126in patients with type2diabetes and impaired glucose tolerance was decreased obviously, but it is unclear that whether it’s secondary to the metabolic disturbance of type2diabetes mellitus or it’s a factor in the development of type2diabetes mellitus. Because type1diabetes is a simplified diabetes which is lack of insulin, so it’s useful to reveal the relationship between miRNA–126and type1diabetes that explore the change of miRNA-126in type1diabetes.ObjectiveTo detect the expression level of plasma miRNA-126in patients with type1diabetes mellitus and analyze the relationship between miRNA-126and the known risk factors of diabetes mellitus. To explore the clinical significance of miRNA-126in the pathophysiological mechanism of the development of type1diabetes, provide new ideas for the pathogenetic and therapeutic targets of type1diabetes.(1) Objective groups: T1DM group contains27patients with type1diabetes, including11cases which was diagnosed as latent autoimmune diabetes in adults(LADA),6cases was newly diagnosed,4cases with microvascular complication(diabetic nephropathy), and8cases with macrovascular complication(atherosclerosis). And the control group includes32healthy controls.(2) General clinical data: collect the age、blood pressure、BMI、FPG、2hPG、HbA1C、HDL-C、LDL-C、TG and TC of both groups, and determine the FCP、2hCP and hs-CRP of T1DM group.(3) Plasma miRNA-126was detected with quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and eNOS was measured with enzyme-linked immunosorbent assay（ELISA）.(4) The relationship between plasma miRNA-126and T1DM risk factors was analyzed by correlation analysis. The main influence factors of miRNA-126was analyzed by multiple stepwise regression analysis.(5) SPSS19.0statistical software was applied for the data statistics. The experimental data was expressed with the meant standard deviation, Two Independent Sample t-test was employed to test the difference between two groups. The pair-wise correlations were analyzed by Pearson correlation analysis or partial correlation analysis. A α value of0.05was considered statistically significant.Results(1) Compared with the control group, the expression level of plasma miRNA-126in T1DM group was significantly decreased(p<0.05).(2) Correlation analysis showed miRNA-126was positively correlated with FCP、2hCP、HDL-C、eNOS, and negatively correlated with hs-CRP、LDL-C、TC and age, and no obvious relationship with BMI、SBP、DBP、FPG、2hPG、HbA1C and TG.(3) The multiple stepwise regression analysis showed that hs-CRP、FCP、TC and age were the independent influencing factors of miRNA-126. Conclusions(1) Compared with the control group, miRNA-126expression level was decreased in plasma in patients with type1diabetes mellitus, which may act as a new quantitative index biomarker for the clinical diagnosis and risk factor evaluation of type1diabetes mellitus.(2) The expression of miRNA-126was correlated to various diabetes related risk factors such as inflammation and lipid metabolic disorders, which showed that miRNA-126may participate in the development of type1diabetes mellitus.