Enhanced P-selectin expression and increased soluble CD40 Ligand in patients with Type 1 diabetes mellitus and microangiopathy: evidence for platelet hyperactivity and chronic inflammation

Diabetologia. 2004 Mar;47(3):537-540. doi: 10.1007/s00125-004-1352-4. Epub 2004 Feb 13.

Abstract

Aims/hypothesis: Platelet activation, endothelial dysfunction and inflammation may be involved in early stages of diabetic microangiopathy. We therefore investigated patients with Type 1 diabetes mellitus, without ( n=19) and with ( n=20) microangiopathy, matched for glycaemic control and duration of disease, and matched with healthy control subjects ( n=27).

Methods: Platelet activation was measured as platelet P-selectin expression using whole blood flow cytometry and as soluble P-selectin by immunoassay. Von Willebrand factor antigen in plasma, serum soluble E-selectin, CD40 ligand (sCD40L) and C-reactive protein (CRP) served as markers for endothelial function and inflammation.

Results: Thrombin-induced platelet P-selectin expression was enhanced, and soluble P-selectin and sCD40L concentrations were increased in patients with microangiopathy compared with the control subjects ( p<0.01 for both) and with patients without microangiopathy ( p<0.05 for P-selectin expression and sP-selectin), whereas all three parameters were similar in patients without microangiopathy and in the control subjects. CRP and soluble E-selectin were increased in patients with microangiopathy, compared with the control subjects ( p<0.01 and p<0.05), whereas von Willebrand factor did not differ between the groups.

Conclusions/interpretation: Microangiopathy in Type 1 diabetes is associated with platelet hyperactivity, endothelial dysfunction and low-grade inflammation, indicating an increased risk for cardiovascular disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Blood Platelets / drug effects
  • Blood Platelets / physiology*
  • Blood Pressure
  • CD40 Ligand / genetics*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetic Angiopathies / genetics
  • Diabetic Angiopathies / immunology
  • Diabetic Angiopathies / physiopathology*
  • Female
  • Humans
  • Inflammation / physiopathology*
  • Male
  • P-Selectin / genetics*
  • Platelet Aggregation / physiology
  • Reference Values
  • Thrombin / pharmacology
  • Triglycerides / blood

Substances

  • Blood Glucose
  • P-Selectin
  • Triglycerides
  • CD40 Ligand
  • Thrombin