Dan Ye1, Tianbao Zhang2, Guohua Lou2, Weiwei Xu1, Fengqin Dong1, Guoping Chen1, Yanning Liu3. 1. Department of Endocrinology and Metabolism, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China. 2. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China. 3. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: liuyanning@zju.edu.cn.
Abstract
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 × WHR-1.121 × miR122 + 1.988 × 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.
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 × WHR-1.121 × miR122 + 1.988 × 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.