The Role of Hypoxia-Sensitive miRNA181a, miRNA199a, SIRT1, and Adiponectin in Diabetes Mellitus Type 2 Development in...

Obstructive sleep apnea (OSA) is a chronic respiratory disorder characterized by intermittent hypoxia and is strongly associated with the development of type 2 diabetes mellitus (T2DM). Despite this link, the molecular mechanisms underlying OSA-related metabolic dysregulation remain incompletely understood. The aim of the study was to investigate the role of hypoxia-sensitive microRNAs, sirtuin 1 (SIRT1), and adiponectin in the metabolic profile of OSA patients, with and without T2DM. A total of 87 participants were stratified into three groups: OSA, OSA + T2DM, and healthy controls. Blood samples were collected in the evening and morning, and after continuous positive airway pressure (CPAP) therapy. Expression levels of miRNAs and SIRT1 were measured via RT-qPCR; adiponectin was quantified by ELISA. Significantly reduced expression of miRNA-181a and miRNA-199a was observed in the OSA + T2DM group compared to OSA (p = 0.035 and p = 0.042, respectively). In contrast, SIRT1 expression was highest in the OSA + T2DM group (p < 0.01), while adiponectin concentrations was lowest in this group and the highest among healthy controls (p = 0.001). Despite increased SIRT1 in OSA + T2DM patients, the parallel increase in adiponectin was not observed. Additionally, expression of SIRT1 was significantly increased in OSA patients who were taking metformin (n = 23) vs. patients without metformin (n = 32) 77.315 vs. 437.08 (p = 0.037). CPAP therapy had significant influence only on miRNA-181a-expression was increased after long-term treatment (p = 0.047). Increased miRNA-181a expression in patients with OSA is related to decreased SIRT1 expression, which may lead to T2DM development. Surprisingly, the expression of SIRT1 is significantly higher and expression of hypoxia-sensitive miRNAs is significantly lower in patients with already developed T2DM, which might be explained by metformin intake.