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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1161/01.CIR.0000074043.46437.44 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The roles of mitochondria in global and local intracellular calcium signalling.
Nat Rev Mol Cell Biol
January 2025
MitoCare Center, Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
Activation of Ca channels in Ca stores in organelles and the plasma membrane generates cytoplasmic calcium ([Ca]) signals that control almost every aspect of cell function, including metabolism, vesicle fusion and contraction. Mitochondria have a high capacity for Ca uptake and chelation, alongside efficient Ca release mechanisms. Still, mitochondria do not store Ca in a prolonged manner under physiological conditions and lack the capacity to generate global [Ca] signals.
View Article and Find Full Text PDFEffect of anthocyanin rich black sugarcane on milk production and antioxidant capacity in lactating dairy cows.
Sci Rep
January 2025
School of Animal Technology and Innovation, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima, 30000, Thailand.
This study aimed to explore the effect of anthocyanin-rich black sugarcane on milk production, plasma antioxidant capacity, and the storage period DPPH scavenging capacity of milk in lactating dairy cows. Sixteen lactating dairy cows were stratified and randomly assigned into two balanced dietary groups, namely Anthocyanin-rich black sugarcane (AS), and Napier grass (NG). The AS group demonstrated a significant decrease (p < 0.
View Article and Find Full Text PDFChemigenetic Ca2+ indicators report elevated Ca2+ levels in endothelial Weibel-Palade bodies.
PLoS One
January 2025
Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, Muenster, Germany.
Weibel-Palade bodies (WPB) are secretory organelles exclusively found in endothelial cells and among other cargo proteins, contain the hemostatic von-Willebrand factor (VWF). Stimulation of endothelial cells results in exocytosis of WPB and release of their cargo into the vascular lumen, where VWF unfurls into long strings of up to 1000 µm and recruits platelets to sites of vascular injury, thereby mediating a crucial step in the hemostatic response. The function of VWF is strongly correlated to its structure; in order to fulfill its task in the vascular lumen, VWF has to undergo a complex packing/processing after translation into the ER.
View Article and Find Full Text PDFAssociation of rapid eye movement sleep latency with multimodal biomarkers of Alzheimer's disease.
Alzheimers Dement
January 2025
Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, California, USA.
Introduction: Sleep disturbances are associated with Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD), but the relationship between sleep architecture, particularly rapid eye movement (REM) sleep, and AD/ADRD biomarkers remains unclear.
Methods: We enrolled 128 adults (64 with Alzheimer's disease, 41 with mild cognitive impairment [MCI], and 23 with normal cognition [NC]), mean age 70.8 ± 9.
Adult hypophosphatasia presenting with recurrent acute joint pain.
Endocrinol Diabetes Metab Case Rep
January 2025
Summary: Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!