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Circulating small non‐coding RNAs are associated with the insulin‐resistant and obesity‐related type 2 diabetes clusters.

Authors :
de Klerk, Juliette A.
Beulens, Joline W. J.
Bijkerk, Roel
van Zonneveld, Anton Jan
Elders, Petra J. M.
't Hart, Leen M.
Slieker, Roderick
Source :
Diabetes, Obesity & Metabolism; Oct2024, Vol. 26 Issue 10, p4375-4385, 11p
Publication Year :
2024

Abstract

Aim: To uncover differences in small non‐coding RNAs (sncRNAs) in individuals with type 2 diabetes (T2D) categorized into five clusters based on individual characteristics, which may aid in the identification of those prone to rapid progression. Materials and Methods: In the Hoorn Diabetes Care System (DCS) cohort, participants were clustered by age, body mass index (BMI), and glycated haemoglobin, C‐peptide and high‐density lipoprotein (HDL) cholesterol levels, yielding severe insulin‐deficient diabetes, severe insulin‐resistant diabetes (SIRD), mild obesity‐related diabetes (MOD), mild diabetes, and mild diabetes with high HDL cholesterol clusters (n = 412). Utilizing plasma sncRNA‐sequencing, we identified distinct cluster‐specific sncRNAs. Validation was performed in a smaller DCS Hoorn dataset (n = 138). To elucidate their potential functions, we examined tissue expression, identified potential targets or (co‐)regulated proteins, conducted gene set enrichment analyses on the targets through Reactome, and examined tissue expression of the (co‐)regulated proteins. Results: The insulin‐resistant cluster exhibited aberrant expression of 10 sncRNAs, while the high BMI cluster featured eight differentially expressed sncRNAs. Multiple (co‐)regulated proteins were identified for sncRNAs associated with both clusters. Proteins associated with both clusters showed enrichment for metabolism. Proteins that specifically and only associated with the SIRD cluster showed enrichment for immune‐related signalling. Furthermore, MOD cluster‐specific associated proteins showed enrichment for the complement system. Conclusions: Our research showed differential sncRNA levels among type 2 diabetes clusters. This may reflect and could deepen our understanding of molecular mechanisms, in development, progression, and risk factors for each cluster. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14628902
Volume :
26
Issue :
10
Database :
Complementary Index
Journal :
Diabetes, Obesity & Metabolism
Publication Type :
Academic Journal
Accession number :
179713533
Full Text :
https://doi.org/10.1111/dom.15786