MicroRNA-126 and micro-/macrovascular complications of type 1 diabetes in the EURODIAB Prospective Complications Study.
OBJECTIVE
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.
Diabetic Nephropathy Laboratory, Department of Medical Sciences, University of Turin, C/so Dogliotti 14, 10126, Turin, Italy. federica.barutta@unito.it.
Federica
http://orcid.org/0000-0001-9319-5123
F
Barutta
Diabetic Nephropathy Laboratory, Department of Medical Sciences, University of Turin, C/so Dogliotti 14, 10126, Turin, Italy.
Graziella
G
Bruno
Diabetic Nephropathy Laboratory, Department of Medical Sciences, University of Turin, C/so Dogliotti 14, 10126, Turin, Italy.|Human Genetics Foundation (HuGeF), Turin, Italy.
Giuseppe
G
Matullo
Institute of Cardiovascular Science, University College London, London, UK.
Nish
N
Chaturvedi
Diabetic Nephropathy Laboratory, Department of Medical Sciences, University of Turin, C/so Dogliotti 14, 10126, Turin, Italy.
Serena
S
Grimaldi
Department of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Casper
C
Schalkwijk
Department of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Coen D
CD
Stehouwer
Department of Epidemiology and Public-Health, Royal Free and University College London, Medical School, London, UK.
John H
JH
Fuller
Diabetic Nephropathy Laboratory, Department of Medical Sciences, University of Turin, C/so Dogliotti 14, 10126, Turin, Italy.
Gabriella
G
Gruden
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D003925:Diabetic Angiopathies / Q000097:blood*; D003930:Diabetic Retinopathy / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
D015415:Biomarkers; C527111:MIRN126 microRNA, human; D035683:MicroRNAs
Complications; MicroRNAs; Retinopathy; Type 1 diabetes