Dataset Information

Plasma extrachromosomal circular DNA is a pathophysiological hallmark of short-term intensive insulin therapy for type 2 diabetes.

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.

SUBMITTER: Xu Z

PROVIDER: S-EPMC10587738 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Plasma extrachromosomal circular DNA is a pathophysiological hallmark of short-term intensive insulin therapy for type 2 diabetes.

Xu Zhe Z He Junyu J Han Peng P Dai Peiji P Lv Wei W Lv Wei W Liu Nian N Liu Liyi L Liu Liehua L Pan Xiaoguang X Xiang Xi X Li Hanbo H Ge Fangfang F Gao Shan S Liao Zhihong Z Luo Yonglun Y Li Yanbing Y

Clinical and translational medicine 20231001 10

<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>We conduc ...[more]

PMID: 37859516

Similar Datasets

Project description:ObjectiveShort-term intensive insulin therapy (IIT) early in the course of type 2 diabetes acutely improves beta-cell function with long-lasting effects on glycemic control. However, conventional measures cannot determine which patients are better suited for IIT, and little is known about the molecular mechanisms determining response. Therefore, this study aimed to develop a model that could accurately predict the response to IIT and provide insight into molecular mechanisms driving such response in humans.MethodsTwenty-four patients with early type 2 diabetes were assessed at baseline and four weeks after IIT, consisting of basal detemir and premeal insulin aspart. Twelve individuals had a beneficial beta-cell response to IIT (responders) and 12 did not (nonresponders). Beta-cell function was assessed by multiple methods, including Insulin Secretion-Sensitivity Index-2. MicroRNAs (miRNAs) were profiled in plasma samples before and after IIT. The response to IIT was modeled using a machine learning algorithm and potential miRNA-mediated regulatory mechanisms assessed by differential expression, correlation, and functional network analyses (FNA).ResultsBaseline levels of circulating miR-145-5p, miR-29c-3p, and HbA1c accurately (91.7%) predicted the response to IIT (OR = 121 [95% CI: 6.7, 2188.3]). Mechanistically, a previously described regulatory loop between miR-145-5p and miR-483-3p/5p, which controls TP53-mediated apoptosis, appears to also occur in our study population of humans with early type 2 diabetes. In addition, significant (fold change > 2, P < 0.05) longitudinal changes due to IIT in the circulating levels of miR-138-5p, miR-192-5p, miR-195-5p, miR-320b, and let-7a-5p further characterized the responder group and significantly correlated (|r| > 0.4, P < 0.05) with the changes in measures of beta-cell function and insulin sensitivity. FNA identified a network of coordinately/cooperatively regulated miRNA-targeted genes that potentially drives the IIT response through negative regulation of apoptotic processes that underlie beta cell dysfunction and concomitant positive regulation of proliferation.ConclusionsResponses to IIT in people with early type 2 diabetes are associated with characteristic miRNA signatures. This study represents a first step to identify potential responders to IIT (a current limitation in the field) and provides important insight into the pathophysiologic determinants of the reversibility of beta-cell dysfunction. ClinicalTrial.gov identifier: NCT01270789.

Dataset Information

Plasma extrachromosomal circular DNA is a pathophysiological hallmark of short-term intensive insulin therapy for type 2 diabetes.

Background

Objective

Methods

Results

Conclusion

Publications

Plasma extrachromosomal circular DNA is a pathophysiological hallmark of short-term intensive insulin therapy for type 2 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets