Soluble CD40 ligand levels in essential hypertensive men: evidence of a possible role of insulin resistance.
BACKGROUND
Elevated levels of the proinflammatory cytokine soluble CD40 ligand (sCD40L) were reported in subjects with diabetes, impaired glucose tolerance, metabolic syndrome (MS), obesity, and insulin resistance. Metabolic abnormalities might also account for increased sCD40L in subjects with essential hypertension.


METHODS
Several metabolic and vascular correlates of sCD40L levels have been investigated in 90 nondiabetic never-treated essential hypertensive men.


RESULTS
Median sCD40L level was 8.7 ng/ml (interquartile range: 4.9-11.7). On the basis of sCD40L, subjects were divided by tertiles (thresholds at 6.6 and 11.0 ng/ml). The three groups did not differ for age, body mass index (BMI), smokers, blood pressure (BP), prevalence of nondippers, lipids and lipoproteins, renal function, and albuminuria. Carotid intima-media thickness (IMT: 0.79 +/- 0.22, 0.83 +/- 0.29, and 0.85 +/- 0.30 mm) and percentage of subjects with wall thickening (IMT >0.9 to <1.3 mm: 23, 27, and 27%, respectively) were superimposable in the three groups. No differences were observed in high-sensitivity C-reactive protein (hs-CRP) and no correlation emerged between sCD40L and hs-CRP. An increase through sCD40L tertiles emerged for basal insulin (11.2 +/- 5.6, 14.7 +/- 7.7, and 16.8 +/- 13.5 microU/ml, P = 0.10) and fasting glucose (95 +/- 11, 103 +/- 16, and 105 +/- 14 mg/dl, P = 0.028). Consistently, along with the increase in sCD40L, a worsening in insulin sensitivity was observed, which was expressed as homeostasis model assessment for insulin sensitivity (HOMA%S: 99 +/- 52, 77 +/- 43, and 72 +/- 35, P < 0.05), composite insulin sensitivity index (ISIcomp; Matsuda index: 5.11 +/- 2.65, 3.61 +/- 1.98, and 3.28 +/- 1.87, P = 0.025), or oral glucose insulin sensitivity (OGIS) index (OGIS: 421 +/- 67, 386 +/- 90, and 362 +/- 72, P = 0.004).


CONCLUSIONS
In newly diagnosed hypertensive men, sCD40L levels are inversely related to insulin sensitivity, with no correlation with BP, other cardiovascular risk factors, or the degree of subclinical atherosclerosis.
Penno
Giuseppe
G
Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. pgiuse@immr.med.unipi.it
Pucci
Laura
L
Dell'Omo
Giulia
G
Lucchesi
Daniela
D
Miccoli
Roberto
R
Del Prato
Stefano
S
Solini
Anna
A
Pedrinelli
Roberto
R
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood*; D017536:Carotid Artery, Common / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012995:Solubility; D017539:Tunica Intima / Q000473:pathology
D001786:Blood Glucose; D023201:CD40 Ligand