Original Paper

Soluble CD40 Ligand, Plasminogen Activator Inhibitor-1 and Thrombin-Activatable Fibrinolysis Inhibitor-1-Antigen in Normotensive Type 2 Diabetic Subjects without Diabetic Complications
Effects of Metformin and Rosiglitazone
Serkan Yener^a, Abdurrahman Comlekci^a, Baris Akinci^a, Tevfik Demir^a, Faize Yuksel^b, Mehmet Ali Ozcan^b, Firat Bayraktar^a, Sena Yesil^a

Divisions of
^aEndocrinology and Metabolism and
^bHematology, Department of Internal Medicine, Dokuz Eylul University School of Medicine, Izmir, Turkey

Address of Corresponding Author

Med Princ Pract 2009;18:266-271 (DOI: 10.1159/000215722)

  Key Words

• Plasminogen activator inhibitor-1
• Soluble CD40 ligand
• Thrombin-activatable fibrinolysis inhibitor
• Metformin
• Rosiglitazone

  Abstract

Objective: To evaluate subclinical inflammation and fibrinolysis in low-risk type 2 diabetic subjects and to assess the efficacy of metformin and rosiglitazone in this group. Subjects and Methods: Sixty-one normotensive, normoalbuminuric type 2 diabetic subjects without diabetes-related complications were included in a 4-week standardization period with glimepiride. After the standardization period, 21 subjects were excluded and the remaining 40 were randomly divided into two groups matched for age, gender, body mass index and disease duration. The first group (n = 20) received metformin (1,700 mg/day), the second group (n = 20) rosiglitazone (4 mg/day) for 12 weeks. Patients with low-density lipoprotein-cholesterol higher than 130 mg/dl at the beginning of the randomization period were treated with simvastatin (maximum dose 20 mg/day). Twenty-three healthy controls were also recruited. Cytokine measurements were performed with ELISA kits. Results: Baseline plasma plasminogen activator inhibitor-1 (PAI-1) level of type 2 diabetic subjects was significantly elevated (p = 0.038), but baseline levels of soluble CD40 ligand (sCD40L) and thrombin-activatable fibrinolysis inhibitor-1 (TAFI) antigen did not differ from healthy controls. Twelve weeks of metformin or rosiglitazone therapy did not cause significant changes in sCD40L, PAI-1 and TAFI antigen levels. In simvastatin-treated subjects (n = 9) significant reductions of PAI-1 were achieved (p = 0.028), while sCD40L and TAFI-Ag did not differ from baseline values. Conclusion: Our results showed that nonobese diabetic patients at low cardiovascular risk had similar levels of subclinical markers of inflammation and fibrinolysis as matched healthy controls. Neither metformin nor rosiglitazone caused marked changes in sCD40L, PAI-1 and TAFI antigen levels. A subset of patients who received simvastatin showed a modest decrease in PAI-1 level and could contribute to beneficial vasculoprotective effect of the drug in type 2 diabetics.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

Serkan Yener
Dokuz Eylul University School of Medicine, Department of Internal Medicine
Division of Endocrinology and Metabolism, Inciralti
TR–35340 Izmir (Turkey)
Tel. +90 232 412 3701, Fax +90 232 279 2267, E-Mail serkan.yener@deu.edu.tr

  Article Information

Received: September 21, 2008
Revised: December 3, 2008
Published online: June 02, 2009
Number of Print Pages : 6
Number of Figures : 0, Number of Tables : 2, Number of References : 29