Upregulation of CD40--CD40 ligand system in patients with diabetes mellitus

Clin Chim Acta. 2004 Jan;339(1-2):85-90. doi: 10.1016/j.cccn.2003.09.007.

Abstract

Background: Diabetes is associated with an increased risk of cardiovascular disease and atherosclerosis. Increasing evidence shows that CD40-CD40L interaction plays a crucial role in the pathogenesis of atherosclerosis and coronary artery disease. The purpose of this study was to assess whether CD40 system expressions were disrupted in patients with diabetes.

Methods: Sixteen normal controls and 72 patients including 20 with type 2 diabetes mellitus (DM), 15 with type 1 DM, 20 with coronary heart disease (CHD) and 17 CHD with coexisting DM were investigated. The expression of CD40 and CD40L on platelet was analyzed by indirect-immunofluorescence flow cytometry and serum-soluble CD40L level was determined by a commercially available ELISA. Serum of AGE was detected by fluorescence spectroscopy.

Results: Type 1 DM, type 2 DM, CHD and CHD Patients with coexisting diabetes showed a significant increase of CD40 (81.8 +/- 11.7, 70.7 +/- 11.6, 68.5 +/- 10.2, 79.9 +/- 11.9 MIF, respectively) and CD40L (18.4 +/- 5.1, 13.9 +/- 4.1, 13.5 +/- 3.7, 16.7 +/- 4.7 MIF, respectively) coexpression on platelets as well as sCD40L (15.6 +/- 3.5, 14.1 +/- 3.3, 12.2 +/- 3.5, 13.5 +/- 3.6 ng/ml, respectively) compared with controls (p < 0.01). A positive correlation was found between serum AGE levels in patients with DM and CD40-CD40L system. We also observed a significant correlation between hemoglobinA1c (HbA1c) concentration and CD40L on platelets (r = 0.71, p < 0.001) as well as sCD40L (r = 0.69, p < 0.001), but not for CD40 on platelets.

Conclusions: Patients with diabetes show increased coexpression of CD40 system, especially CD40L, which may create a proinflammatory and prothrombotic milieu for aggravating the development of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / analysis
  • Blood Platelets / metabolism
  • CD40 Antigens / blood*
  • CD40 Antigens / metabolism
  • CD40 Ligand / blood*
  • CD40 Ligand / metabolism
  • Diabetes Mellitus / blood*
  • Diabetes Mellitus / metabolism
  • Hemoglobin A / analysis
  • Humans
  • Middle Aged
  • Solubility

Substances

  • Blood Glucose
  • CD40 Antigens
  • CD40 Ligand
  • Hemoglobin A