Fukui M, Ose H, Kitagawa Y, Yamazaki M, Hasegawa G, Yoshikawa T, Nakamura N. Relationship between low serum endogenous androgen concentrations and arterial stiffness in men with type 2 diabetes mellitus

Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kawaramachi-Hirokoji, Kyoto, Japan.
Metabolism (Impact Factor: 3.89). 09/2007; 56(9):1167-73. DOI: 10.1016/j.metabol.2007.04.011
Source: PubMed


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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    • "Arterial stiffness increases with advancing age (Vaitkevicius et al., 1993; Hougaku et al., 2006), and elevated central arterial stiffness is a predictor of CVD and all-cause mortality (Laurent et al., 2001; Sutton- Tyrrell et al., 2005; Cohn, 2006). It has been reported that serum DHEA concentration is inversely associated with arterial stiffness (Dockery et al., 2003b; Hougaku et al., 2006; Fukui et al., 2007) and that DHEA has a number of effects that would be expected to prevent and reverse the stiffening of cardiovascular system tissues. These include inhibition of vascular smooth muscle cell proliferation, attenuation of collagen production by cardiac fibroblasts and reduction in left ventricular stiffness, activation of arterial endothelial cell nitric oxide synthase, increase in arterial endothelial cell proliferation and inhibition of arterial endothelial cell apoptosis , and inhibition of vascular inflammation (Liu & Dillon, 2002; Williams et al., 2002, 2004; Iwasaki et al., 2005; Alwardt et al., 2006; Liu et al., 2007; Bonnet et al., 2009). "
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    ABSTRACT: Serum dehydroepiandrosterone (DHEA) concentrations decrease approximately 80% between ages 25 and 75 year. Aging also results in an increase in arterial stiffness, which is an independent predictor of cardiovascular disease (CVD) risk and mortality. Therefore, it is conceivable that DHEA replacement in older adults could reduce arterial stiffness. We sought to determine whether DHEA replacement therapy in older adults reduces carotid augmentation index (AI) and carotid-femoral pulse wave velocity (PWV) as indices of arterial stiffness. A randomized, double-blind trial was conducted to study the effects of 50 mg day(-1) DHEA replacement on AI (n = 92) and PWV (n = 51) in women and men aged 65-75 year. Inflammatory cytokines and sex hormones were measured in fasting serum. AI decreased in the DHEA group, but not in the placebo group (difference between groups, -6 ± 2 AI units, P = 0.002). Pulse wave velocity also decreased (difference between groups, -3.5 ± 1.0 m s(-1) , P = 0.001); however, after adjusting for baseline values, the between-group comparison became nonsignificant (P = 0.20). The reductions in AI and PWV were accompanied by decreases in inflammatory cytokines (tumor necrosis factor α and IL-6, P < 0.05) and correlated with increases in serum DHEAS (r = -0.31 and -0.37, respectively, P < 0.05). The reductions in AI also correlated with free testosterone index (r = -0.23, P = 0.03). In conclusion, DHEA replacement in elderly men and women improves indices of arterial stiffness. Arterial stiffness increases with age and is an independent risk factor for CVD. Therefore, the improvements observed in this study suggest that DHEA replacement might partly reverse arterial aging and reduce CVD risk.
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    • "Further, a low plasma testosterone level appeared to be associated with endothelial dysfunction in men independent of other risk factors, suggesting a protective effect of endogenous testosterone on the endothelium[5]. In addition, serum endogenous androgen concentrations were inversely associated with arterial stiffness in men with type 2 diabetes mellitus[6]. There is an association of type 2 diabetes with low testosterone values, and therefore, the effects of an intervention with testosterone are of considerable interest. "
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    ABSTRACT: Lower extremity complications (neuropathy, ulceration, infection, and peripheral arterial disease) are common in diabetes mellitus. There is an inverse relation between plasma testosterone and insulin sensitivity, type 2 diabetes mellitus and HbA1c concentrations. We report the beneficial effects of administration of testosterone to three men with a diabetic foot whose serum testosterone was subnormal. Upon normalization of serum testosterone there was an improvement of hyperglycemia, a decrease of leukocytes and of fibrinogen levels, an increase of antithrombin III activity and of tissue oxygen pressure. The wound showed granulation. Beneficial effects of administration of testosterone to hypogonadal with a diabetic foot may be due to improved vascularization and to anti-inflammatory action.
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