Endothelial dysfunction markers as a therapeutic target for Sildenafil treatment and effects on metabolic control in type 2 diabetes

Expert Opin Ther Targets. 2015;19(12):1617-22. doi: 10.1517/14728222.2015.1066337. Epub 2015 Jul 15.

Abstract

Objective: Endothelial dysfunction (ED) plays a role in diabetic cardiovascular complications. Hyperglycemia increases cytockines involved in vascular inflammation. Inhibition of phosphodiesterase type 5 (PDE5) exerts a relaxation on corpora cavernosa and has cardioprotective properties. The effect of chronic sildenafil treatment, on ED markers and metabolic parameters in a non-randomized study on men with type 2 diabetes (T2DM), was investigated.

Research design and methods: Twenty-eight T2DM patients (61.2 ± 7.8 years, hemoglobin A1c (HbA1c) 7.9 ± 1.3%, duration of diabetes 11.5 ± 7.8 years) were treated with sildenafil 100 mg/d for 3 months. Baseline and postprandial glycemia, insulin, HbA1c, HOMA index, lipids, glomerular filtration rate, homocysteine were assessed at each visit. P-selectin (CD62P), CD14/42b, CD14/41, ICAM (CD54), PECAM (CD31) and CD11b/CD18, were evaluated, after monocyte isolation with flow-cytometry, before and after treatment.

Results: After 3 months, sildenafil decreased P-selectin (p < 0.05), post-prandial glycemia (p < 0.01), HbA1c (p < 0.01), low-density lipoprotein cholesterol (p < 0.01) and increased high-density lipoprotein (p < 0.05).

Conclusions: PDE5 inhibition, in T2DM patients, reduces the endothelial function marker P-selectin and exerts a beneficial effect on glycometabolic control.

Trial registration: ClinicalTrials.gov NCT00692237.

Keywords: P-selectin; phosphodiesterase type-5 inhibitors; sildenafil; type 2 diabetes.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / pathology
  • Glycated Hemoglobin
  • Humans
  • Hyperglycemia / drug therapy
  • Insulin / metabolism
  • Lipids / blood
  • Male
  • Middle Aged
  • P-Selectin / metabolism
  • Phosphodiesterase 5 Inhibitors / pharmacology
  • Sildenafil Citrate / pharmacology*
  • Vasodilator Agents / pharmacology*

Substances

  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Lipids
  • P-Selectin
  • Phosphodiesterase 5 Inhibitors
  • Vasodilator Agents
  • Sildenafil Citrate

Associated data

  • ClinicalTrials.gov/NCT00692237