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J Clin Endocrinol Metab. 2018 Jan 23. doi: 10.1210/jc.2017-01417. [Epub ahead of print]

Two novel microRNA biomarkers related to β-cell damage and their potential values for early diagnosis of type 1 diabetes.

Liu L1,2,3, Yan J1,2, Xu H1,2, Zhu Y4, Liang H1,2, Pan W1,2, Yao B1,2, Han X4, Ye J5, Weng J1,2.

Author information

Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China.
Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
Antioxidant and Gene Regulation Lab, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.



New strategies and biomarkers are needed in the early detection of β-cell damage in the progress of type 1 diabetes mellitus (T1DM).


To explore whether serum microRNAs should be served as biomarkers for T1DM.

Design, Settings and Patients:

The serum microRNA profile was established with microRNA microarray in discovery phase (6 T1DM, 6 controls). A microRNA-based model for T1DM diagnosis was developed using logistic regression analysis in the training dataset (40 T1DM, 56 controls) and then validated with leave-one-out cross validation and another independent validation dataset (33 T1DM, 29 controls).

Main Outcome Measure(s):

Quantitative RT-PCR was applied to confirm the differences of candidate microRNAs between T1DM and controls. Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. INS-1 cells, streptozocin-treated mice (n=4) and NOD mice (n=12) were used to evaluate the association of microRNAs with β-cell damage.


A microRNA-based model was established in the training dataset with high diagnostic accuracy for T1DM (AUC=0.817) based on six candidate differential expressed microRNAs identified in discovery phase. The validation dataset showed the model's satisfactory diagnostic performance (AUC=0.804). Secretions of miR-1225-5p and miR-320c were significantly increased in streptozocin-treated mice and INS-1 cells. Noteworthy, the elevation of these two microRNAs was observed before glucose elevation in the progress of diabetes in NOD mice.


Two microRNA biomarkers (miR-1225-5p and miR-320c) related to β-cell damage were identified in recent-onset T1DM patients. The microRNA-based model established in this study exhibited a good performance in diagnosis of T1DM.


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