MicroRNA-126 and micro-/macrovascular complications of type 1 diabetes in the EURODIAB Prospective Complications Study.

Abstract

Increasing evidence suggests a potential role of circulating miRNAs as clinical biomarkers, and loss of miRNA-126 has been proposed as a predictor of type 2 diabetes onset. However, a systematic analysis of circulating miRNAs in type 1 diabetic patients with micro-/macrovascular complications has not yet been performed. A cross-sectional nested case-control study from the EURODIAB Prospective Complications Study of 455 type 1 diabetic patients was performed. Case subjects (n=312) were defined as those with one or more complications of diabetes; control subjects (n=143) were those with no evidence of any complication. A differential miRNA expression profiling was performed in pooled serum samples from cases and controls. Furthermore, miR-126 levels were quantified by qPCR in all individual samples and associations with diabetic complications investigated. Twenty-five miRNAs differed in pooled samples from cases and controls. miR-126 levels were significantly lower in case than in control subjects, even after adjustment for age and sex. In logistic regression analyses, miR-126 was negatively associated with all complications (OR=0.85, 95% CI 0.75-0.96) as well as with each micro-/macrovascular complication examined separately. This was likely dependent of diabetes as associations were no longer significant after adjustment for both hyperglycemia and diabetes duration. However, a significant 25% risk reduction, independent of age, sex, A1C, and diabetes duration, was still observed for proliferative retinopathy (OR=0.75, 95% CI 0.59-0.95). In this large cohort of type 1 diabetic subjects, we found that miR-126 levels are associated with vascular complications of diabetes, particularly with proliferative retinopathy.