Predicting gestational diabetes mellitus risk at 11-13 weeks' gestation: the role of extrachromosomal circular DNA.

Cardiovasc Diabetol

Prenatal Diagnosis Center, Jinan Maternal and Child Health Care Hospital, No.2, Jianguo Xiaojing Roud, Jinan, 250002, Shandong Province, People's Republic of China.

Published: August 2024

AI Article Synopsis

  • Gestational diabetes mellitus (GDM) poses risks to both mothers and infants, highlighting the need for early diagnostic biomarkers, with extrachromosomal circular DNA (eccDNA) being a promising candidate.
  • In this study, plasma eccDNA profiles were analyzed in women who later developed GDM, identifying 2,217 differentially expressed eccDNAs, with PRDM16 showing significant potential for early diagnosis at 11-13 weeks of gestation.
  • The findings suggest that eccDNA, particularly PRDM16, may serve as an effective biomarker for early screening of GDM, paving the way for improved maternal and infant health outcomes.

Article Abstract

Background: Gestational diabetes mellitus (GDM) significantly impacts maternal and infant health both immediately and over the long term, yet effective early diagnostic biomarkers are currently lacking. Thus, it is essential to identify early diagnostic biomarkers for GDM risk screening. Extrachromosomal circular DNA (eccDNA), being more stable than linear DNA and involved in disease pathologies, is a viable biomarker candidate for diverse conditions. In this study, eccDNA biomarkers identified for early diagnosis and assessment of GDM risk were explored.

Methods: Using Circle-seq, we identified plasma eccDNA profiles in five pregnant women who later developed GDM and five matched healthy controls at 11-13 weeks of gestation. These profiles were subsequently analyzed through bioinformatics and validated through outward PCR combined with Sanger sequencing. Furthermore, candidate eccDNA was validated by quantitative PCR (qPCR) in a larger cohort of 70 women who developed GDM and 70 normal glucose-tolerant (NGT) subjects. A ROC curve assessed the eccDNA's diagnostic potential for GDM.

Results: 2217 eccDNAs were differentially detected between future GDM patients and controls, with 1289 increased and 928 decreased in abundance. KEGG analysis linked eccDNA genes mainly to GDM-related pathways such as Rap1, MAPK, and PI3K-Akt, and Insulin resistance, among others. Validation confirmed a significant decrease in eccDNA PRDM16 in the plasma of 70 women who developed GDM compared to 70 NGT women, consistent with the eccDNA-seq results. PRDM16 showed significant diagnostic value in 11-13 weeks of gestation (AUC = 0.941, p < 0.001).

Conclusions: Our study first demonstrats that eccDNAs are aberrantly produced in women who develop GDM, including PRDM16, which can predict GDM at an early stage of pregnancy, indicating its potential as a biomarker.

Trial Registration: ChiCTR2300075971, http://www.chictr.org.cn . Registered 20 September 2023.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304788PMC
http://dx.doi.org/10.1186/s12933-024-02381-1DOI Listing

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