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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Markolf Hanefeld - , Department of Internal Medicine 3, GWT-TUD GmbH (Author)
  • Katrin Engelmann - , Klinikum Chemnitz gGmbH, Institute of Anatomy (Author)
  • Dieter Appelt - , GWT-TUD GmbH (Author)
  • Dirk Sandner - , Department of Ophthalmology, University Hospital Carl Gustav Carus Dresden (Author)
  • Ingo Weigmann - , GWT-TUD GmbH (Author)
  • Xenia Ganz - , GWT-TUD GmbH (Author)
  • Frank Pistrosch - , GWT-TUD GmbH, Department of Internal Medicine 3 (Author)
  • Carsta Köhler - , GWT-TUD GmbH (Author)
  • Antje Gasparic - , GWT-TUD GmbH (Author)
  • Andreas L. Birkenfeld - , Department of Internal Medicine III, German Center for Diabetes Research - Paul Langerhans Insitute Dresden (Partner: HMGU), University Hospital Carl Gustav Carus Dresden, German Center for Diabetes Research (DZD e.V.), King's College London (KCL), GWT-TUD GmbH (Author)

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.

Details

Original languageEnglish
Article numbere0184234
JournalPloS one
Volume12
Issue number10
Publication statusPublished - Oct 2017
Peer-reviewedYes

External IDs

PubMed 28991900