title: Plasma level of miR-93 is associated with higher risk to develop type 2 diabetic retinopathy.
abstract: OBJECTIVE
  MicroRNA-93 (miR-93) usually acts as a promoter of tumor progression in several human carcinomas. It has been found distinctly high in eyes with proliferative diabetic retinopathy (DR). The present study aims to investigate the role of plasma miR-93 in the progression of type 2 diabetic retinopathy (T2DR).
  
  
  METHODS
  Our study subjects were made up of 140 type 2 diabetes mellitus (T2DM) patients who were assigned into DR (DR patients, n = 75), NDR (non-DR patients, n = 65), and control (healthy individuals, n = 127) groups. Levels of fasting blood glucose (FBG), fasting plasma glucose (FPG), triglyceride (TG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), blood urea nitrogen (BUN), creatinine (Cr), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and fasting insulin (FIsn) were detected by automatic biochemical analyzer. Enzyme-linked immunosorbent assay (ELISA) was performed for the levels of interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF), qRT-PCR for the miR-93 expression in plasma, and mRNA expressions of IL-1, IL-6, TNF-α and VEGF; receiver operating characteristic (ROC) curve for the diagnostic performance of miR-93 to T2DR, Pearson correlation analysis for correlation analysis between miR-93 and other indexes detected before and multivariate logistic regression analyses for the risk factors for T2DR.
  
  
  RESULTS
  The DR and NDR groups exhibited elevated course of disease, and decreased levels of FBG, FPG, TG, HbA1c, TC, BUN, Cr, HDL-C, FIsn, IL-1, IL-6, TNF-α and VEGF but declined LDL-C level as compared to the control group. The course of disease was longer and the levels of FBG, FPG, HbA1c, IL1, IL6 and VEGF were higher in the DR group than those in the NDR group (all P < 0.05). The miR-93 expression and RNA expressions of IL-1, IL-6, TNF-α and VEGF were higher in the DR group than those in the NDR group (P < 0.05). The best cutoff for miR-93 to assess T2DR was 1.31, with a Youden index of 0.63, sensitivity of 73.33%, specificity of 89.24%, and area under the curve (AUC) of 0.866. Pearson correlation analysis indicated that miR-93 expression was positively associated with course of disease, the levels of FPG, HbA1c, TNF-α and VEGF. T2DM patients with longer disease course, higher levels of FBG, HbA1c, VEGF and miR-93 expression were risk factors for developing DR.
  
  
  CONCLUSIONS
  Our study demonstrates that plasma miR-93 is associated with the progression of T2DR and it can sever as a diagnostic marker for T2DR.
authors.affiliation: Department of Endocrinology and Metabolism, Suqian People's Hospital, Nanjing Drum Tower Hospital, No. 138, South Yellow River Road, Suqian, 223800, Jiangsu Province, People's Republic of China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Zou
authors.affiliation: Department of Geriatrics, Suqian People's Hospital, Nanjing Drum Tower Hospital, Suqian, 223800, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Suqian People's Hospital, Nanjing Drum Tower Hospital, No. 138, South Yellow River Road, Suqian, 223800, Jiangsu Province, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gang
authors.affiliation: Department of Endocrinology and Metabolism, Suqian People's Hospital, Nanjing Drum Tower Hospital, No. 138, South Yellow River Road, Suqian, 223800, Jiangsu Province, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Suqian People's Hospital, Nanjing Drum Tower Hospital, No. 138, South Yellow River Road, Suqian, 223800, Jiangsu Province, People's Republic of China. sqsunyu@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003930:Diabetic Retinopathy / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines; C543350:MIRN93 microRNA, human; D035683:MicroRNAs
keywords: Diagnosis; MicroRNA-93; Sensitivity; Specificity; Type 2 diabetes mellitus; Type 2 diabetic retinopathy