Effect of rosiglitazone treatment on soluble CD40L in patients with type 2 diabetes and coronary artery disease.
BACKGROUND
Interaction of CD40L with its receptor CD40 is critically involved in inflammatory cell activation in atherogenesis. In addition, serum levels of soluble CD40L are elevated in acute coronary syndromes and have been associated with increased cardiovascular risk in healthy subjects, thus making sCD40L an intriguing target to modulate the inflammatory response in the vasculature. PPARgamma-activating thiazolidinediones, novel insulin-sensitizing antidiabetic agents, have recently been shown to exhibit antiinflammatory effects in the vessel wall. To examine whether thiazolidinedione treatment might modulate serum levels of sCD40L in high-risk patients, we performed a randomized, placebo-controlled, single-blinded trial to assess the effect of rosiglitazone on sCD40L levels in patients with type 2 diabetes and coronary artery disease (CAD).


RESULTS
Thirty-nine patients with diabetes and angiographically proven CAD were randomized to receive rosiglitazone (4 mg BID) or placebo for 12 weeks. Baseline parameters did not significantly differ between groups. Rosiglitazone treatment, but not placebo, significantly reduced sCD40L serum levels within the first 2 weeks by 8.1% (17.1 to -32.7) (median percentage [interquartile range]; P<0.05 compared with baseline), further decreasing it by 18.4% (-5.0 to -33.1) after 6 weeks (P<0.05 compared with baseline), and by 27.5% (8.2 to -70.5) after 12 weeks (P<0.05 compared with baseline and with 2 weeks of treatment).


CONCLUSIONS
Treatment with the PPARgamma-activating thiazolidinedione rosiglitazone reduces sCD40L serum levels in patients with type 2 diabetes and CAD. These data support an antiinflammatory and potentially antiatherogenic effect of thiazolidinediones.
Marx
Nikolaus
N
Department of Internal Medicine II-Cardiology, University of Freiburg, Germany. nikolaus.marx@medizin.uni-ulm.de
Imhof
Armin
A
Froehlich
Johannes
J
Siam
Laila
L
Ittner
Jochen
J
Wierse
Gerhard
G
Schmidt
Arnold
A
Maerz
Winfried
W
Hombach
Vinzenz
V
Koenig
Wolfgang
W
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D023201:CD40 Ligand / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D019040:E-Selectin / Q000097:blood; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D015375:Receptors, Interleukin-2 / Q000097:blood; D012016:Reference Values; D000077154:Rosiglitazone; D012995:Solubility; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D013995:Time; D014157:Transcription Factors / Q000819:agonists; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use
D015415:Biomarkers; D001786:Blood Glucose; D023201:CD40 Ligand; D019040:E-Selectin; D005343:Fibrinolytic Agents; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D015375:Receptors, Interleukin-2; D000077154:Rosiglitazone; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014665:Vasodilator Agents