DNA methylation and exosomes in relation to type 2 diabetes in Black South Africans: A pilot study

Abstract

Type 2 diabetes (T2D) is a metabolic disorder characterised by hyperglycaemia, reduced insulin secretion, and increased insulin resistance, yet its mechanisms are not fully understood. While genetic predisposition contributes to the variable disease presentation across different ethnic populations, it does not fully explain the burden of T2D. Global 5-methylcytosine (5-mC) has emerged as an important regulator of gene expression, influencing disease pathogenesis through interactions with environmental factors. In parallel, circulating exosomes have attracted significant attention in research due to their role in mediating cell-to-cell communication and their capability to transport bioactive molecules, including methylated genomic DNA, that influence gene expression and metabolic pathways. The combined contribution of 5-mC and circulating exosome concentration to T2D pathogenesis in African populations remains poorly understood. A South African community case-control study of 40 T2D cases and 40 healthy controls quantified exosomes and 5-mC using their corresponding enzyme-linked immunosorbent assay. Associations of variables with T2D were evaluated using linear and logistic regression models. Serum exosome concentrations were positively correlated with global 5-mC (r = 0.269, p = 0.016). Global 5-mC levels were positively associated with triglycerides (r = 0.232, p = 0.038) and inversely correlated with weight in the diabetic group (r = -0.342, p = 0.038), while exosomes showed a sex-specific inverse association with diastolic blood pressure in males (r = -0.585, p = 0.028). However, neither biomarker independently predicted T2D after adjustment for confounders. These findings suggest a modest interplay between epigenetic modification and exosome signalling, warranting further investigation in larger studies.

Keywords

Type 2 diabetes / Global DNA methylation / Exosomes / Peripheral blood / Biomarker / South Africa

Author contributions

BBM wrote the draft, performed the laboratory experiments and analysed data. LTP critically reviewed and revised manuscript, SS made substantial contributions to acquisition of data and performed the laboratory experiments, HM reviewed manuscript and analysed data, YYY conceived research project, reviewed manuscript and supervisor. All authors approved and read the final manuscript.

Consent for publication

Not applicable.

Ethical approval and consent

The study was conducted in accordance to the Code of Ethics of the World Medical Association (Declaration of Helsinki). Ethical approval was obtained from the Faculty of Health Sciences Research and Ethics committee of the Walter Sisulu University (046/2022). All participants signed an informed consent form after the study purpose and all procedures had been fully explained in their home language.

Funding

This work was supported by the National Research Foundation and South African Medical Research Council.

Data availability

Data are available from the corresponding author upon request.

Declaration of Competing Interest

The authors declare that they have no competing interests.

Acknowledgements

The authors would like to thank all participants who voluntarily agreed to participate in this study.

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