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

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.