Plasma extrachromosomal circular DNA is a pathophysiological hallmark of short-term intensive insulin therapy for type 2 diabetes.
Clin Transl Med
; 13(10): e1437, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37859516
ABSTRACT
BACKGROUND:
Extrachromosomal circular DNA (eccDNA) has emerged as a promising biomarker for disease diagnosis and prognosis prediction. However, its role in type 2 diabetes remains unexplored.OBJECTIVE:
To investigate the characteristics and dynamics of circulating eccDNAs in newly diagnosed type 2 diabetes mellitus (T2DM) patients undergoing short-term intensive insulin therapy (SIIT), a highly effective treatment for inducing long-term glycemic remission.METHODS:
We conducted Circle-Seq analysis on plasma samples from 35 T2DM patients at three time points pre-SIIT, post-SIIT, and 1-year post-SIIT. Our analysis encompassed the characterization of eccDNA features, including GC content, eccDNA length distribution, genomic distribution, and the genes in eccDNAs.RESULTS:
Following SIIT, we observed an increase in plasma eccDNA load, suggesting metabolic alterations during therapy. Notably, a correlation was identified between eccDNA profiles and glycemia in T2DM, both quantitatively and genetically. Our analysis also revealed the frequent presence of metabolism-related genes within T2DM plasma eccDNAs, some of which spanned gene exons and/or fractions.CONCLUSION:
This study represents the first report of cell-free eccDNA in T2DM and underscores a compelling association between cell-free eccDNA and profound glycemic changes. These findings highlight the potential of eccDNAs as crucial players in the context of T2DM and glycemic control.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Insulina
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article