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.
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.


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.


CONCLUSIONS
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.
Yener
Serkan
S
Division of Endocrinology and Metabolism, Department of Internal Medicine, Dokuz Eylul University School of Medicine, Izmir, Turkey. serkan.yener@deu.edu.tr
Comlekci
Abdurrahman
A
Akinci
Baris
B
Demir
Tevfik
T
Yuksel
Faize
F
Ozcan
Mehmet Ali
MA
Bayraktar
Firat
F
Yesil
Sena
S
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D023201:CD40 Ligand / Q000378:metabolism*; D025901:Carboxypeptidase B2 / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D000077154:Rosiglitazone; D019821:Simvastatin / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D007004:Hypoglycemic Agents; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D023201:CD40 Ligand; D008687:Metformin; D019821:Simvastatin; D025901:Carboxypeptidase B2