Relationship between plasma levels of soluble CD40L and insulin sensitivity and insulin secretion status in non-diabetic dyslipidemic patients.
OBJECTIVE
We have measured circulating plasma sCD40L as well as the platelet-surface of CD40L and its receptor in a sample of non-diabetic dyslipidemic patients and then evaluated its relationship with the insulin resistance (IR) and insulin secretion (IS) status.


METHODS
Anthropometric measurements, fasting glucose, insulin, lipids, and IR and IS [estimated by the homeostasis model assessment (HOMA)] were assessed in 86 dyslipidemic subjects. Circulating sCD40L were determined by ELISA. By flow cytometry, CD40L, CD40 and P-selectin were evaluated in the platelet-surface.


RESULTS
Non-diabetic dyslipidemic IR patients (HOMA-IR>or=3.8) showed higher plasma sCD40L concentrations and a more unfavorable cardiovascular risk profile (higher BMI, waist, fasting insulin and mean triglyceride levels) than dyslipidemic patients with low IS (HOMA beta-cell<98). In a multivariable model, only measures of insulin sensitivity and higher waist remained significantly associated with increased plasma levels of sCD40L. Surface expression of CD40L on platelets decreased significantly and CD40 increased in IR patients, compared with patients with low IS.


CONCLUSIONS
IR dyslipidemic patients show increased plasma sCD40L and decreased platelet-membrane CD40L expression compared to dyslipidemic patients with low IS.
Filozof
Claudia
C
Lipid Clinic, Area of Prevention and Cardiovascular Rehabilitation, Cardiovascular Institute, Hospital Clínico San Carlos-UCM, Madrid, Spain.
Gómez-Garre
Dulcenombre
D
Reinares
Leonardo
L
González-Rubio
María Luisa
ML
Muñoz-Pacheco
Paloma
P
Rueda
Antonio
A
Alvarez-Arcaya
Arántzazu
A
Calle-Pascual
Alfonso L
AL
Fernández-Cruz
Arturo
A
D000328:Adult; D001792:Blood Platelets / Q000502:physiology; D001794:Blood Pressure; D049628:Body Size; D001835:Body Weight; D023201:CD40 Ligand / Q000097:blood*; D050171:Dyslipidemias / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D023201:CD40 Ligand