Federica Barutta1, Graziella Bruno2, Giuseppe Matullo2,3, Nish Chaturvedi4, Serena Grimaldi2, Casper Schalkwijk5, Coen D Stehouwer5, John H Fuller6, Gabriella Gruden2. 1. Diabetic Nephropathy Laboratory, Department of Medical Sciences, University of Turin, C/so Dogliotti 14, 10126, Turin, Italy. federica.barutta@unito.it. 2. Diabetic Nephropathy Laboratory, Department of Medical Sciences, University of Turin, C/so Dogliotti 14, 10126, Turin, Italy. 3. Human Genetics Foundation (HuGeF), Turin, Italy. 4. Institute of Cardiovascular Science, University College London, London, UK. 5. Department of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. 6. Department of Epidemiology and Public-Health, Royal Free and University College London, Medical School, London, UK.
Abstract
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.
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 diabeticpatients 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 diabeticpatients 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.
Entities:
Keywords:
Complications; MicroRNAs; Retinopathy; Type 1 diabetes