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From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures

Background and aim—Alterations in circulating microRNA (miRNA) expression patterns are thought to be involved in the early stages of prediabetes, as well as in the progression to overt type 2 diabetes mellitus (T2D) and its vascular complications. However, most research findings are conflicting, in...

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Autores principales: Greco, Marta, Mirabelli, Maria, Salatino, Alessandro, Accattato, Francesca, Aiello, Vincenzo, Brunetti, Francesco S., Chiefari, Eusebio, Pullano, Salvatore A., Fiorillo, Antonino S., Foti, Daniela P., Brunetti, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377827/
https://www.ncbi.nlm.nih.gov/pubmed/37510186
http://dx.doi.org/10.3390/diagnostics13142443
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author Greco, Marta
Mirabelli, Maria
Salatino, Alessandro
Accattato, Francesca
Aiello, Vincenzo
Brunetti, Francesco S.
Chiefari, Eusebio
Pullano, Salvatore A.
Fiorillo, Antonino S.
Foti, Daniela P.
Brunetti, Antonio
author_facet Greco, Marta
Mirabelli, Maria
Salatino, Alessandro
Accattato, Francesca
Aiello, Vincenzo
Brunetti, Francesco S.
Chiefari, Eusebio
Pullano, Salvatore A.
Fiorillo, Antonino S.
Foti, Daniela P.
Brunetti, Antonio
author_sort Greco, Marta
collection PubMed
description Background and aim—Alterations in circulating microRNA (miRNA) expression patterns are thought to be involved in the early stages of prediabetes, as well as in the progression to overt type 2 diabetes mellitus (T2D) and its vascular complications. However, most research findings are conflicting, in part due to differences in miRNA extraction and normalization methods, and in part due to differences in the study populations and their selection. This cross-sectional study seeks to find new potentially useful biomarkers to predict and/or diagnose T2D by investigating the differential expression patterns of circulating miRNAs in the serum of patients with impaired fasting glucose (IFG) and new-onset T2D, with respect to euglycemic controls, using a high-throughput 384-well array and real-time PCR. Methods—Thirty subjects, aged 45–65 years, classified into three matched groups (of 10 participants each) according to their glycometabolic status, namely (1) healthy euglycemic controls, (2) patients with IFG and (3) patients with new-onset, uncomplicated T2D (<2 years since diagnosis) were enrolled. Circulating miRNAs were extracted from blood serum and profiled through real-time PCR on a commercial 384 well-array, containing spotted forward primers for 372 miRNAs. Data analysis was performed by using the online data analysis software GeneGlobe and normalized by the global Ct mean method. Results—Of the 372 analyzed miRNAs, 33 showed a considerably different expression in IFG and new-onset T2D compared to healthy euglycemic controls, with 2 of them down-regulated and 31 up-regulated. Stringent analysis conditions, using a differential fold regulation threshold ≥ 10, revealed that nine miRNAs (hsa-miR-3610, hsa-miR-3200-5p, hsa-miR-4651, hsa-miR-3135b, hsa-miR-1281, hsa-miR-4301, hsa-miR-195-5p, hsa-miR-523-5p and hsa-let-7a-5p) showed a specific increase in new-onset T2D patients compared to IFG patients, suggesting their possible role as early biomarkers of progression from prediabetes to T2D. Moreover, by conventional fold regulation thresholds of ±2, hsa-miR-146a-5p was down-regulated and miR-1225-3p up-regulated in new-onset T2D patients only. Whereas hsa-miR-146a-5p has a well-known role in glucose metabolism, insulin resistance and T2D complications, no association between hsa-miR-1225-3p and T2D has been previously reported. Bioinformatic and computational analysis predict a role of hsa-miR-1225-3p in the pathogenesis of T2D through the interaction with MAP3K1 and HMGA1. Conclusions—The outcomes of this study could aid in the identification and characterization of circulating miRNAs as potential novel biomarkers for the early diagnosis of T2D and may serve as a proof-of-concept for future mechanistic investigations.
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spelling pubmed-103778272023-07-29 From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures Greco, Marta Mirabelli, Maria Salatino, Alessandro Accattato, Francesca Aiello, Vincenzo Brunetti, Francesco S. Chiefari, Eusebio Pullano, Salvatore A. Fiorillo, Antonino S. Foti, Daniela P. Brunetti, Antonio Diagnostics (Basel) Article Background and aim—Alterations in circulating microRNA (miRNA) expression patterns are thought to be involved in the early stages of prediabetes, as well as in the progression to overt type 2 diabetes mellitus (T2D) and its vascular complications. However, most research findings are conflicting, in part due to differences in miRNA extraction and normalization methods, and in part due to differences in the study populations and their selection. This cross-sectional study seeks to find new potentially useful biomarkers to predict and/or diagnose T2D by investigating the differential expression patterns of circulating miRNAs in the serum of patients with impaired fasting glucose (IFG) and new-onset T2D, with respect to euglycemic controls, using a high-throughput 384-well array and real-time PCR. Methods—Thirty subjects, aged 45–65 years, classified into three matched groups (of 10 participants each) according to their glycometabolic status, namely (1) healthy euglycemic controls, (2) patients with IFG and (3) patients with new-onset, uncomplicated T2D (<2 years since diagnosis) were enrolled. Circulating miRNAs were extracted from blood serum and profiled through real-time PCR on a commercial 384 well-array, containing spotted forward primers for 372 miRNAs. Data analysis was performed by using the online data analysis software GeneGlobe and normalized by the global Ct mean method. Results—Of the 372 analyzed miRNAs, 33 showed a considerably different expression in IFG and new-onset T2D compared to healthy euglycemic controls, with 2 of them down-regulated and 31 up-regulated. Stringent analysis conditions, using a differential fold regulation threshold ≥ 10, revealed that nine miRNAs (hsa-miR-3610, hsa-miR-3200-5p, hsa-miR-4651, hsa-miR-3135b, hsa-miR-1281, hsa-miR-4301, hsa-miR-195-5p, hsa-miR-523-5p and hsa-let-7a-5p) showed a specific increase in new-onset T2D patients compared to IFG patients, suggesting their possible role as early biomarkers of progression from prediabetes to T2D. Moreover, by conventional fold regulation thresholds of ±2, hsa-miR-146a-5p was down-regulated and miR-1225-3p up-regulated in new-onset T2D patients only. Whereas hsa-miR-146a-5p has a well-known role in glucose metabolism, insulin resistance and T2D complications, no association between hsa-miR-1225-3p and T2D has been previously reported. Bioinformatic and computational analysis predict a role of hsa-miR-1225-3p in the pathogenesis of T2D through the interaction with MAP3K1 and HMGA1. Conclusions—The outcomes of this study could aid in the identification and characterization of circulating miRNAs as potential novel biomarkers for the early diagnosis of T2D and may serve as a proof-of-concept for future mechanistic investigations. MDPI 2023-07-21 /pmc/articles/PMC10377827/ /pubmed/37510186 http://dx.doi.org/10.3390/diagnostics13142443 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Greco, Marta
Mirabelli, Maria
Salatino, Alessandro
Accattato, Francesca
Aiello, Vincenzo
Brunetti, Francesco S.
Chiefari, Eusebio
Pullano, Salvatore A.
Fiorillo, Antonino S.
Foti, Daniela P.
Brunetti, Antonio
From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures
title From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures
title_full From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures
title_fullStr From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures
title_full_unstemmed From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures
title_short From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures
title_sort from euglycemia to recent onset of type 2 diabetes mellitus: a proof-of-concept study on circulating microrna profiling reveals distinct, and early microrna signatures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377827/
https://www.ncbi.nlm.nih.gov/pubmed/37510186
http://dx.doi.org/10.3390/diagnostics13142443
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