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J Clin Endocrinol Metab. 2018 Apr 1;103(4):1320-1329. doi: 10.1210/jc.2017-01417.

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

Author information

1
Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
2
Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
3
Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China.
4
Key Laboratory of Human Functional Genomics of Jiangsu Province, Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
5
Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana.

Abstract

Context:

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

Objective:

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

Design, Settings, and Patients:

The miRNA profile was established with miRNA microarray in discovery phase (six T1DM, six controls). A miRNA-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 Measures:

Quantitative reverse transcription polymerase chain reaction was applied to confirm the differences of candidate miRNAs between T1DM and controls. Area under the receiver-operating characteristic (ROC) curve (AUC) was used to evaluate diagnostic accuracy. INS-1 cells, streptozotocin-treated mice (n = 4), and nonobese diabetic (NOD) mice (n = 12) were used to evaluate the association of miRNAs with β-cell damage.

Results:

A miRNA -based model was established in the training dataset with high diagnostic accuracy for T1DM (AUC = 0.817) based on six candidate differential expressed miRNAs 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 streptozotocin-treated mice and INS-1 cells. Noteworthy, the elevation of these two miRNAs was observed before glucose elevation in the progress of diabetes in NOD mice.

Conclusions:

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

PMID:
29370422
DOI:
10.1210/jc.2017-01417
[Indexed for MEDLINE]

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