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

• Published in: Acta diabetologica Vol. 54; no. 2; pp. 133 - 139
• Main Authors: Barutta, Federica, Bruno, Graziella, Matullo, Giuseppe, Chaturvedi, Nish, Grimaldi, Serena, Schalkwijk, Casper, Stehouwer, Coen D., Fuller, John H., Gruden, Gabriella
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 01-02-2017; Springer Nature B.V
• Subjects: Adolescent; Adult; Biomarkers - blood; Case-Control Studies; Cross-Sectional Studies; Diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - complications; Diabetic Angiopathies - blood; Diabetic Retinopathy - blood; Female; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Metabolic Diseases; MicroRNAs - blood; Middle Aged; Original Article; Prospective Studies; Ribonucleic acid; Risk Factors; RNA; Vascular endothelial growth factor; Retinopathy; Type 1 diabetes; Complications; MicroRNAs
• ISSN: 0940-5429; 1432-5233
• DOI: 10.1007/s00592-016-0915-4

Aims
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.
Methods
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.
Results
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).
Conclusions
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.