PMID- 32664305 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2077-0383 (Print) IS - 2077-0383 (Electronic) IS - 2077-0383 (Linking) VI - 9 IP - 7 DP - 2020 Jul 10 TI - Circulating miRNAs as a Predictive Biomarker of the Progression from Prediabetes to Diabetes: Outcomes of a 5-Year Prospective Observational Study. LID - 10.3390/jcm9072184 [doi] LID - 2184 AB - Due to a global increase in the prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need for early identification of prediabetes, as these people have the highest risk of developing diabetes. Circulating miRNAs have shown potential as progression biomarkers in other diseases. This study aimed to conduct a baseline comparison of serum-circulating miRNAs in prediabetic individuals, with the distinction between those who later progressed to T2DM and those who did not. The expression levels of 798 miRNAs using NanoString technology were examined. Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression modeling were performed. Gene ontology (GO) and canonical pathway analysis were used to explore the biological functions of the miRNA target genes. The study revealed that three miRNAs were upregulated in the serum samples of patients who later progressed to T2DM. Pathway analysis showed that the miRNA target genes were mainly significantly enriched in neuronal NO synthase (nNOS) signaling in neurons, amyloid processing, and hepatic cholestasis. ROC analysis demonstrated that miR-491-5p, miR-1307-3p, and miR-298 can be introduced as a diagnostic tool for the prediction of T2DM (area under the curve (AUC) = 94.0%, 88.0%, and 84.0%, respectively). Validation by real-time quantitative polymerase chain reaction (qRT-PCR) confirmed our findings. The results suggest that circulating miRNAs can potentially be used as predictive biomarkers of T2DM in prediabetic patients. FAU - Sidorkiewicz, Iwona AU - Sidorkiewicz I AUID- ORCID: 0000-0003-0254-3095 AD - Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland. FAU - Niemira, Magdalena AU - Niemira M AUID- ORCID: 0000-0002-0701-4961 AD - Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland. FAU - Maliszewska, Katarzyna AU - Maliszewska K AUID- ORCID: 0000-0001-5721-2571 AD - Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland. FAU - Erol, Anna AU - Erol A AUID- ORCID: 0000-0002-9932-5176 AD - Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland. FAU - Bielska, Agnieszka AU - Bielska A AD - Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland. FAU - Szalkowska, Anna AU - Szalkowska A AD - Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland. FAU - Adamska-Patruno, Edyta AU - Adamska-Patruno E AUID- ORCID: 0000-0002-8805-0744 AD - Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland. FAU - Szczerbinski, Lukasz AU - Szczerbinski L AUID- ORCID: 0000-0002-6201-0605 AD - Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland. AD - Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland. FAU - Gorska, Maria AU - Gorska M AD - Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland. FAU - Kretowski, Adam AU - Kretowski A AUID- ORCID: 0000-0002-4522-4978 AD - Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland. AD - Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, 15-276 Bialystok, Poland. LA - eng PT - Journal Article DEP - 20200710 PL - Switzerland TA - J Clin Med JT - Journal of clinical medicine JID - 101606588 PMC - PMC7408684 OTO - NOTNLM OT - biomarker OT - diabetes OT - miRNA OT - prediabetes OT - serum profiling COIS- The authors declare no conflicts of interest. EDAT- 2020/07/16 06:00 MHDA- 2020/07/16 06:01 PMCR- 2020/07/10 CRDT- 2020/07/16 06:00 PHST- 2020/06/10 00:00 [received] PHST- 2020/07/01 00:00 [revised] PHST- 2020/07/07 00:00 [accepted] PHST- 2020/07/16 06:00 [entrez] PHST- 2020/07/16 06:00 [pubmed] PHST- 2020/07/16 06:01 [medline] PHST- 2020/07/10 00:00 [pmc-release] AID - jcm9072184 [pii] AID - jcm-09-02184 [pii] AID - 10.3390/jcm9072184 [doi] PST - epublish SO - J Clin Med. 2020 Jul 10;9(7):2184. doi: 10.3390/jcm9072184.