Relationship between low serum endogenous androgen concentrations and arterial stiffness in men with type 2 diabetes mellitus.
ABSTRACT The aim of this study was to evaluate the relationship between arterial stiffness determined by pulse wave velocity (PWV) and serum endogenous androgen concentrations as well as major cardiovascular risk factors in men with type 2 diabetes mellitus. Serum free testosterone and dehydroepiandrosterone sulfate (DHEA-S) concentrations were measured in 268 men with type 2 diabetes mellitus. Relationships between PWV and serum endogenous androgen concentrations as well as major cardiovascular risk factors, including age, blood pressure, serum lipid concentration, glycemic control (hemoglobin A(1c)), body mass index, and degree of albuminuria, were evaluated. Positive correlations were found between PWV and age (r = 0.491, P < .0001), duration of diabetes (r = 0.320, P < .0001), systolic blood pressure (r = 0.292, P < .0001), and log (urinary albumin excretion) (r = 0.269, P < .0001). Inverse correlations were found between serum free testosterone concentration and PWV (r = -0.228, P = .0003) and between serum DHEA-S concentration and PWV (r = -0.252, P = .0002) in men with type 2 diabetes mellitus. Pulse wave velocity was significantly greater in patients with lower concentrations of free testosterone (<10 pg/mL) than in patients with higher concentrations of free testosterone (1864 +/- 359 vs 1736 +/- 327 cm/s; P = .0053). Pulse wave velocity also was significantly greater in patients with lower concentrations of DHEA-S (<1000 ng/mL) than in patients with higher concentrations of DHEA-S (1843 +/- 371 vs 1686 +/- 298 cm/s; P = .0008). Multiple regression analysis identified both serum free testosterone concentration (beta = -.151, P = .0150) and serum DHEA-S concentration (beta = -.200, P = .0017) as independent determinants of PWV. In conclusion, serum endogenous androgen concentrations are inversely associated with arterial stiffness determined by PWV in men with type 2 diabetes mellitus, which is true for men in general based on other works.
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ABSTRACT: Development of microalbuminuria increases the risk for cardiovascular disease (CVD) in type 2 diabetes. The nature of this relationship is unclear but may involve arterial stiffness, an independent risk marker for CVD mortality. Aortic pulse wave velocity (Ao-PWV) and albumin creatinine ratio (ACR) were measured in 134 consecutive patients with type 2 diabetes without overt renal impairment (serum creatinine <150 micromol/L). ACR ranged from 0.2 to 153 mg/mmol. Patients with raised ACR (>/=3 mg/mmol) had higher Ao-PWV, poorer diabetic control, and higher pulse pressure (PP) and systolic BP (SBP) (all P < 0.05) than those with normal ACR. The closest univariate associations of Ao-PWV were positively with age, duration of diabetes, SBP, PP, ACR, and insulin treatment and negatively with GFR and weight (all P < 0.01). In a multiple linear step-down regression analysis, the significant predictors of Ao-PWV were age, SBP or PP, duration of diabetes, gender, number of antihypertensive medications, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, which together explained 55% of the variance of Ao-PWV. When ACR was offered in place of arterial pressure to a separate model, ACR emerged as a significant predictor of Ao-PWV. After age adjustment, patients with lower, below median GFR had higher Ao-PWV than those with GFR above the median (P = 0.043). In patients with type 2 diabetes without overt renal impairment, raised ACR is associated with higher Ao-PWV, a relationship most likely mediated by raised BP. The association of Ao-PWV with reduced GFR suggests that even modest renal dysfunction may affect the viscoelastic properties of large arteries.Journal of the American Society of Nephrology 05/2005; 16(4):1069-75. · 8.99 Impact Factor
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ABSTRACT: Diabetes is commonly associated with both microvascular and macrovascular complications. These vascular complications are accelerated in the context of systemic hypertension. During the past few years the underlying molecular mechanisms responsible for diabetic vascular complications have begun to be clarified. It appears that both metabolic and hemodynamic factors interact to stimulate the expression of cytokines and growth factors in the various vascular trees. Overexpression of the prosclerotic cytokine transforming growth factor-beta has been observed in glomeruli and tubules from the diabetic kidney. In the retina the angiogenic cytokine vascular endothelial growth factor and its receptor, vascular endothelial growth factor R-2 are increased in experimental diabetes. These changes in growth factors are viewed to be responsible for the extracellular matrix accumulation in the diabetic kidney and new vessel formation in the diabetic retina. Changes in cytokines have also been observed at other vascular sites including the mesenteric vascular tree. Vasoactive hormones, such as angiotensin II and endothelin, are potent stimulators of cytokines with recent studies showing that inhibitors of these vasoactive hormone pathways may confer organ protection in diabetes by inhibition of growth factor expression. Glucose-dependent factors, such as the formation of advanced glycation end products that interact with specific receptors and lead to overexpression of a range of cytokines, may play an important role in diabetic vascular complications including atherosclerosis. It is likely that the effects of inhibitors of this pathway such as aminoguanidine on cytokine production may play a pivotal role in mediating the renal, retinal, and vasoprotective effects observed with this agent in experimental diabetes. It is anticipated that the advent of specific inhibitors of cytokine formation or action will provide new approaches for the prevention and treatment of diabetic vascular complications.American Journal of Hypertension 06/2001; 14(5 Pt 1):475-86. · 3.67 Impact Factor
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ABSTRACT: This study investigated the effects of hormonal therapy on large arterial properties. Arterial stiffness is an emerging risk marker for coronary heart disease and is potentially modifiable. Postmenopausal use of hormonal therapy is associated with a lower risk of coronary heart disease. Total systemic arterial compliance (SAC) and pulse wave velocity (PWV) were determined in 26 premenopausal and 52 postmenopausal women, 26 of whom were taking hormonal therapy. Arterial compliance was greater in the premenopausal group (mean +/- SEM 0.57 +/- 0.04 arbitrary compliance units [ACU]) than in the postmenopausal group not taking hormonal therapy (0.26 +/- 0.02 ACU, p = 0.001). Postmenopausal women taking hormonal therapy had a significantly increased total SAC compared with women not taking hormonal therapy (0.43 +/- 0.02 vs. 0.26 +/- 0.02 ACU, p = 0.001). PWV in the aortofemoral region in the premenopausal women was 6.0 +/- 0.2 vs. 8.9 +/- 0.3 m/s (p < 0.001) in untreated postmenopausal women. However, postmenopausal women taking hormonal therapy had a significantly lower PWV than those not taking hormonal therapy (7.9 +/- 0.2 vs. 8.9 +/- 0.3 m/s, p = 0.01). Eleven postmenopausal women had their hormone replacement therapy withdrawn for 4 weeks, resulting in a significant decrease in SAC and a significant increase in aortofemoral PWV. The increased SAC and decreased PWV in women receiving hormonal therapy suggest that such therapy may decrease stiffness of the aorta and large arteries in postmenopausal women, with potential benefit for age-related cardiovascular disorders. The reduction of arterial compliance with age appears to be altered with hormonal therapy.Journal of the American College of Cardiology 08/1997; 30(2):350-6. · 14.09 Impact Factor