Hyperglycemia is associated with lower levels of urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor in wound fluid

J Diabetes Complications. 2014 Nov-Dec;28(6):844-9. doi: 10.1016/j.jdiacomp.2014.07.013. Epub 2014 Aug 7.

Abstract

Aims: Wounds in patients with hyperglycemia show impaired healing. Plasminogen activation is crucial in several overlapping phases of wound healing process. In this study, we aimed i) to compare acute wound fluid in patients with hyperglycemia and normoglycemia, ii) to focus on the elements of plasminogen activation in the wound fluid, and iii) to determine if the acute wound fluid characteristics are associated with surgical site infections.

Methods: In a cohort of 54 patients, a closed suction drain was placed in the wound above the anterior abdominal wall fascia under the skin in order to collect postoperative acute wound fluid samples for 3 following days after colorectal surgery. Patients were classified as normoglycemic (n=25) or hyperglycemic (n=29; 17 with type 2 diabetes and 12 with stress induced hyperglycemia). Surgical site infection was defined according to the Centers for Disease Control criteria. The levels of urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAr), plasminogen activator inhibitor-1 (PAI-1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and fibroblast growth factor-1 (FGF-1) were measured in the wound fluid.

Results: Compared to normoglycemic subjects, patients with hyperglycemia had significantly lower levels of uPA and uPAr in the wound fluid despite similar or even higher circulating levels. There was no significant difference in IL-1β, TNF-α, PAI-1 and FGF-1 levels. In the whole study population, the wound fluid levels of uPA and uPAr were negatively correlated with circulating glucose levels. No difference was detected in the wound fluid characteristics of patients with and without surgical site infection.

Conclusion: Patients with hyperglycemia exhibit decreased levels of uPA and uPAr in the wound fluid, suggesting a local failure in plasminogen activation at the wound site.

Keywords: Diabetes; Hyperglycemia; Plasminogen activation; Wound fluid; Wound healing.

Publication types

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

MeSH terms

  • Aged
  • Body Fluids / metabolism*
  • Colorectal Surgery
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / surgery
  • Female
  • Humans
  • Hyperglycemia / complications
  • Hyperglycemia / metabolism*
  • Hyperglycemia / surgery
  • Male
  • Middle Aged
  • Receptors, Urokinase Plasminogen Activator / metabolism*
  • Skin / metabolism
  • Skin / pathology
  • Surgical Wound Infection / complications
  • Surgical Wound Infection / metabolism
  • Urokinase-Type Plasminogen Activator / metabolism*
  • Wound Healing / physiology
  • Wounds and Injuries / metabolism*
  • Wounds and Injuries / pathology

Substances

  • Receptors, Urokinase Plasminogen Activator
  • Urokinase-Type Plasminogen Activator