Microvascular Density and Circulating Endothelial Progenitor Cells Before and After Treatment with Incretin Mimetics in Diabetic Patients

High Blood Press Cardiovasc Prev. 2018 Dec;25(4):369-378. doi: 10.1007/s40292-018-0279-7. Epub 2018 Sep 10.

Abstract

Introduction: Glucagon-like peptide 1-receptor agonists (incretin mimetics) and dipeptidyl peptidase-4 inhibitors (incretin enhancers) have been recently introduced in the treatment of diabetes mellitus. In particular, incretin mimetics seems to have ancillary antioxidant/antinflammatory properties that might be involved in endothelial protection.

Aim: To investigate the effect of incretin mimetic therapy (liraglutide, exenatide) given to 11 patients with type 2 diabetes mellitus, on circulating endothelial progenitor cells (EPCs) (bone marrow-derived cells possibly participating in neovascularization and endothelial protection and repair) and capillary density.

Methods: Four diabetic patients were treated with exenatide (5 μg twice daily for 4 weeks and then 10 μg twice daily for 3 weeks) and 7 with liraglutide (0.6 mg per day for 1 week and then 1.2 mg per day for 3 weeks). Peripheral venous blood samples were obtained before treatment (basal) and after 4 week in patients treated with liraglutide, and after 4 and 7 weeks in patients treated with exenatide, since drug titration is usually longer. EPCs were evaluated by flow cytometry as CD34+/KDR+ cells. Capillary density was evaluated by videomicroscopy, before and after venous congestion, in the dorsum of the 4th finger.

Results: Patients treated with liraglutide (6 males 1 female, age 54 ± 12 years) showed a decrease in body mass index and blood pressure during treatment, while patients treated with exenatide (3 males 1 female, age 57 ± 6 years) did not show any relevant change. EPCs were significantly increased after treatment with exenatide, but not after treatment with liraglutide. Capillary density was slightly increased only after 4 weeks of treatment with exenatide, however the increase was no longer present at the final evaluation.

Conclusions: Treatment with exenatide, but not with liraglutide, was able to increase the number of circulating EPCs, possibly through an antioxidative/antiinflammatory effect.

Keywords: Capillaries; Capillary density; Diabetes mellitus; Endothelial progenitor cells; Exenatide; Incretin mimetics; Liraglutide; Microvascular density.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Capillaries / drug effects*
  • Capillaries / pathology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / pathology
  • Endothelial Progenitor Cells / drug effects*
  • Endothelial Progenitor Cells / metabolism
  • Endothelial Progenitor Cells / pathology
  • Exenatide / administration & dosage*
  • Exenatide / adverse effects
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Incretins / administration & dosage*
  • Incretins / adverse effects
  • Liraglutide / administration & dosage*
  • Liraglutide / adverse effects
  • Male
  • Middle Aged
  • Skin / blood supply*
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Hypoglycemic Agents
  • Incretins
  • Liraglutide
  • Exenatide