Serum MicroRNA-191-5p Levels in Vascular Complications of Type 1 Diabetes: the EURODIAB Prospective Complications Study

Context: MicroRNA-191-5p regulates key cellular processes involved in the pathogenesis of diabetic complications such as angiogenesis, extracellular matrix deposition, and inflammation. However, no data on circulating microRNA-191-5p in the chronic complications of diabetes are currently available. Objective: To assess whether serum levels of miR-191-5p were associated with micro- and macrovascular disease in a large cohort of subjects with type 1 diabetes (DM1) from the EURODIAB Prospective Complication Study (PCS). Design and setting: Levels of microRNA-191-5p were measured by quantitative PCR (qPCR) in 420 DM1 subjects recruited as part of the cross-sectional analysis of the EURODIAB PCS. Cases (n = 277) were subjects with nephropathy and/or retinopathy and/or cardiovascular disease (CVD). Controls (n = 143) were patients without complications. Logistic regression analysis was performed to evaluate the potential independent association of microRNA-191-5p levels with chronic complications of diabetes. Results: Levels of microRNA-191-5p were significantly reduced (P < 0.001) in cases compared to controls even after adjustment for age, sex, and diabetes duration. Logistic regression analysis revealed that microRNA-191-5p was negatively associated with a 58% reduced odd ratio (OR) of chronic diabetes complications, specifically CVD, micro-macroalbuminuria, and retinopathy [OR: 0.42 95% CI (0.23-0.77)], independently of age, sex, physical activity, educational levels, diabetes duration, glycated haemoglobin (HbA1c), total insulin dose, hypertension, smoking, total cholesterol, albumin excretion rate (AER), estimated glomerular filtration rate (eGFR), serum Vascular Cell Adhesion Molecule-1 (sVCAM-1), and tumour necrosis factor-α (TNF-α). Analyses performed separately for each complication demonstrated a significant independent association with albuminuria [OR: 0.36 95% CI (0.18-0.75)], and CVD [OR: 0.34 95% CI (0.16-0.70)]. Conclusions: In DM1 subjects, miR-191-5p is inversely associated with vascular chronic complications of diabetes.