Plasma miR-17, miR-20a, miR-20b and miR-122 as potential biomarkers for diagnosis of NAFLD in type 2 diabetes mellitus patients

Aims: Type 2 diabetes mellitus (T2DM), with non-alcoholic fatty liver disease (NAFLD) complication, may aggravate the disturbance of metabolism, increase the risk of non-alcoholic steatohepatitis, and promote the progress of liver fibrosis. Therefore, early detection of NAFLD in T2DM patients is critical in avoiding the adverse effects of the complication. This study aimed to identify circulating miRNAs for early diagnosis of the complication. Materials and methods: Plasma miRNA expression profiles of T2DM patients complicated with or without NAFLD were examined by miRNA array analysis and then were validated by qRT-PCR. A new index for prediction the presence of NAFLD was developed based on the result of multivariate logistic regression analysis. STZ and high fat diet were used for construction a rat model of T2DM complicated with NAFLD. Key findings: Plasma miR-17, miR-20a, miR-20b, and miR-122 were up-regulated in T2DM patients with NAFLD complicated compared in those without NAFLD (P < 0.05). Moreover, the data from the rat model further showed that the above miRNAs were more sensitive than traditional serological markers for predicting the complication. Meanwhile, in order to improve the diagnostic accuracy, we try to construct an AUC by using the new index, 24.852 x WHR-1.121 x miR122 + 1.988 x LDL-21.838, which was significantly higher than a chance assignment (asymptotic significance P < 0.001) for predicting the presence of NAFLD. Significance: Plasma miRNAs and the new index involving WHR, LDL, and miR-122 are potential novel tools for the early diagnosis and risk estimation of NAFLD in T2DM patients.