Serum vs. exosomal miRNA signatures in South Asian adults with prediabetes: implications for T2DM risk prediction

MicroRNAs are key regulators of metabolic homeostasis, circulating both freely in serum and encapsulated within exosomes, but a direct comparative analysis of their diagnostic potential in prediabetes remains unexplored.

We conducted a cohort study involving individuals with prediabetes (n = 25), newly diagnosed Type 2 Diabetes Mellitus (n = 15), persisting Type 2 Diabetes Mellitus (n = 25), and age-, sex-, and BMI-matched normoglycemic controls (n = 25). RNA was isolated from paired whole serum and serum-derived exosomes, and RT-qPCR was performed to quantify differentially expressed miRNAs (miR-128-3p, miR-15b-5p, miR-6838-5p, miR-195-5p, and miR-424-5p). Diagnostic power of candidate miRNAs was determined using ROC curve analysis.

Distinct miRNA signatures were identified in whole serum and exosomal fractions. miR-195-5p and miR-6838-5p were consistently and significantly upregulated in the prediabetes cohort. Exosomal miRNAs also exhibited distinct changes in both prediabetes and n-T2DM. Their diagnostic performance demonstrated significant ability to differentiate between individuals with prediabetes and normoglycemia.

Our findings indicate that analysis of total serum miRNAs provides a more sensitive and robust approach for identifying individuals with prediabetes, which correlates with the exosomal fraction. Hence, we can infer that miR-195-5p and miR-6838-5p are novel, high-performance circulatory biomarkers detecting T2DM, paving the way for improved risk stratification and preventive strategies.