In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 107, No. 21 ( 2003-06-03), p. 2664-2669
Abstract:
Background— Considerable evidence implicates the proinflammatory cytokine CD40 ligand (CD40L) in atherosclerosis and accumulating data link type 1 and 2 diabetes, conditions associated with accelerated atherosclerosis, to inflammation. This study therefore evaluated the hypothesis that diabetic patients have elevated plasma levels of soluble CD40L (sCD40L) and that treatment with the insulin-sensitizing thiazolidinediones lowers this index of inflammation. Methods and Results— Subjects with type 1 (n=49) or type 2 diabetes (n=48) had higher ( P 〈 0.001) sCD40L plasma levels (6.56±3.27 and 6.67±2.90 ng/mL, respectively) compared with age-matched control groups (1.40±2.21 and 1.32±2.68 ng/mL, respectively). Multiple regression analysis demonstrated a significant ( P 〈 0.001) association between plasma sCD40L and type 1 as well as type 2 diabetes, independent of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, body mass index, gender, C-reactive protein, and soluble intracellular adhesion molecule-1. Furthermore, in a pilot study, administration of troglitazone (12 weeks, 600 mg/day), but not placebo, to type 2 diabetics (n=68) significantly ( P 〈 0.001) diminished sCD40L plasma levels by 29%. The thiazolidinedione lowered plasma sCD40L in type 2 diabetic patients with long-standing disease ( 〉 3 years) with or without macrovascular complications (−34% and −29%, respectively) as well as in type 2 diabetic patients with more recent ( 〈 3 years) onset of the disease (−27%; all P 〈 0.05). Conclusions— This study provides new evidence that individuals with type 1 or 2 diabetes have a proinflammatory state as indicated by elevated levels of plasma sCD40L. Troglitazone treatment of type 2 diabetic patients diminishes sCD40L levels, suggesting a novel antiinflammatory mechanism for limiting diabetes-associated arterial disease.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.0000074043.46437.44
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2003
detail.hit.zdb_id:
1466401-X
