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

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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.

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Acknowledgments

This work was supported by the “European Foundation for the Study of Diabetes.”

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Authors and Affiliations

  1. Diabetic Nephropathy Laboratory, Department of Medical Sciences, University of Turin, C/so Dogliotti 14, 10126, Turin, Italy

    Federica Barutta, Graziella Bruno, Giuseppe Matullo, Serena Grimaldi & Gabriella Gruden

  2. Institute of Cardiovascular Science, University College London, London, UK

    Nish Chaturvedi

  3. Department of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

    Casper Schalkwijk & Coen D. Stehouwer

  4. Department of Epidemiology and Public-Health, Royal Free and University College London, Medical School, London, UK

    John H. Fuller

  5. Human Genetics Foundation (HuGeF), Turin, Italy

    Giuseppe Matullo

Authors
  1. Federica Barutta
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  2. Graziella Bruno
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  3. Giuseppe Matullo
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  4. Nish Chaturvedi
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  5. Serena Grimaldi
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  6. Casper Schalkwijk
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  9. Gabriella Gruden
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Correspondence to Federica Barutta.

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Human and animal rights

All procedures followed were in accordance with the ethical standards of the responsible committee on the human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

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Informed consent was obtained from all individual participants included in the study.

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Barutta, F., Bruno, G., Matullo, G. et al. MicroRNA-126 and micro-/macrovascular complications of type 1 diabetes in the EURODIAB Prospective Complications Study. Acta Diabetol 54, 133–139 (2017). https://doi.org/10.1007/s00592-016-0915-4

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  • DOI: https://doi.org/10.1007/s00592-016-0915-4

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