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PLoS One. 2017 Oct 9;12(10):e0184234. doi: 10.1371/journal.pone.0184234. eCollection 2017.

Intra-individual variability and circadian rhythm of vascular endothelial growth factors in subjects with normal glucose tolerance and type 2 diabetes.

Author information

1
Study Centre Metabolic Vascular Medicine, GWT TU-Dresden GmbH, Dresden, Germany.
2
Medical Clinic III, Universitätsklinikum "Carl Gustav Carus", Technische Universität Dresden, Dresden, Germany.
3
Klinikum Chemnitz gGmbH, Chemnitz, Germany.
4
Experimental Ophthalmology, Institute of Anatomy, Technische Universität Dresden, Dresden, Germany.
5
Clinic for Ophthalmology, Universitätsklinikum "Carl Gustav Carus", Technische Universität Dresden, Dresden, Germany.
6
Medical Consulting, GWT TU-Dresden GmbH, Dresden, Germany.
7
Paul Langerhans Institute Dresden of the Helmholtz Center Munich at University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany.
8
German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
9
Section of Diabetes and Nutritional Sciences, Rayne Institute, Denmark Hill Campus, King's College London, United Kingdom.

Abstract

Increased levels of systemic vascular endothelial growth factors (VEGFs) in patients with diabetes are associated with increased risk of microvessel disease. On the other hand, low VEGF levels after intravitreal antibody application may be associated with acute cardiovascular complications and treatment failure. Individual levels of systemic VEGF vary in a wide range depending on analytical methods and quality of diabetes control. So far only limited information exists on intraindividual fluctuations over longer periods and circadian rhythms. We analysed the intraindividual variance of VEGF-A, VEGF-C and placental growth factor (PLGF) in CTAD (citrate-theophylline-adenine-dipyridamol) plasma as well as VEGF-A in serum over a period of 6 months in patients with stable controlled type 2 diabetes (10 M, 10 F) and age and sex matched subjects with normal glucose tolerance (NGT). Furthermore, circadian levels of VEGFs were controlled hourly from 7:30 a.m. to 7:30 p.m. under standardized metabolic ward conditions. In addition, the relationship to metabolic, hormonal and inflammatory biomarkers was analyzed. VEGF-A, VEGF-C and PLGF remained stable in plasma and VEGF-A in serum over 6 months in both groups. No circadian change was observed in VEGF-A serum and plasma concentrations. A minor decrease of VEGF-C plasma levels was evident after 5 p.m. in both groups and a significant peak of PLGF concentrations occurred after lunch, which was more pronounced in T2DM. In multivariate analysis, only serum VEGF-A correlated to diabetes duration, whereas VEGF-C only correlated to HbA1c and fasting blood glucose. We did not observe significant intraindividual variances for VEGF-A in serum and VEGF-A, VEGF-C and PLGF in CTAD plasma over a period of 6 months. Taken together, a single morning measurement of systemic VEGF levels after 7:30 am appears to be a reliable parameter for the individual risk associated with abnormal VEGF concentrations in blood.

TRIAL REGISTRATION:

NCT02325271.

PMID:
28991900
PMCID:
PMC5633167
DOI:
10.1371/journal.pone.0184234
[Indexed for MEDLINE]
Free PMC Article

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