The Association between Midnight Salivary Cortisol and Metabolic Syndrome in Korean Adults

BackgroundThe common characteristics of metabolic syndrome (MetS) and Cushing's syndrome suggest that excess cortisol may be involved in the pathogenesis of MetS. Salivary cortisol measurements are simple and can be surrogates for plasma free cortisol, which is the most biologically active form. We evaluated the association between levels of midnight salivary cortisol and MetS in Korean adults.MethodsA total of 46 subjects, aged 20 to 70 years, who visited the Health Care Center at Konkuk University Hospital from August 2008 to August 2009 were enrolled. We compared the levels of midnight salivary cortisol in subjects with MetS with those in subjects without MetS. We analyzed the associations between midnight salivary cortisol levels and components of MetS.ResultsMidnight salivary cortisol levels were higher in the MetS group (70±42.4 ng/dL, n=12) than that in the group without MetS (48.1±36.8 ng/dL, n=34) (P=0.001). Positive correlations were observed between midnight salivary cortisol levels and waist circumference, fasting blood glucose, and homeostasis model assessment of insulin resistance. The risk for MetS was significantly higher in subjects with midnight salivary cortisol levels ≥100 ng/dL than in those with levels <50 ng/dL (odds ratio, 5.9; 95% confidence interval, 2.35 to 36.4).ConclusionThe results showed a positive correlation between midnight salivary cortisol levels and MetS, suggesting that hypercortisolism may be related to MetS

Adrenocorticotropic hormone levels before treatment predict recurrence of Cushing's disease

Background/PurposeCushing's disease (CD) is the most common cause of endogenous Cushing's syndrome. Transsphenoidal surgery (TSS) is the first choice of treatment. Predicting prognosis after treatment can benefit further strategies of management, but currently there is no convenient predictor. This study aims to investigate characteristic changes after treatment and to identify potential prognostic predictors.MethodsWe retrospectively studied the records of CD patients presenting to the National Taiwan University Hospital, Taipei, Taiwan between 1992 and 2011. They were categorized according to treatment response. Clinical features and examination findings were compared between groups.ResultsForty-one patients with CD were included. The follow-up time was 0.26–19.3 years. The time interval between the onset of symptoms and diagnosis was 2.1–120.0 months. The initial remission rate of CD after the first treatment was 82.9%. Mean body mass index (BMI) was 27.4 kg/m2 before treatment and 26.0 kg/m2 3 months after treatment. The patients in remission had a greater decrease in BMI after treatment and lower dehydroepiandrosterone sulfate (DHEAS) levels before treatment, compared with the recurrent group (both p < 0.05). Adrenocorticotropic hormone (ACTH) levels before treatment showed a significant positive correlation with recurrent diseases (p < 0.05).ConclusionA larger decrease in BMI after treatment and lower DHEAS levels before treatment were noted for the patients who stayed in CD remission. Higher ACTH levels before treatment predicted a recurrence of CD. These are potentially simple and practical predictors of prognosis

β3-adrenoceptor stimulation of perivascular adipocytes leads to increased fat cell-derived nitric oxide and vascular relaxation in small arteries

BACKGROUND AND PURPOSE In response to norepinephrine healthy perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arterial tissue. Organ bath solution transfer experiments have demonstrated the release of PVAT-derived relaxing factors that mediate this function. The present studies were designed to investigate the mechanism responsible for the norepinephrine-induced PVAT anticontractile effect. EXPERIMENTAL APPROACH In vitro rat small arterial contractile function was assessed using wire myography in the presence and absence of PVAT and the effects of sympathomimetic stimulation on the PVAT environment explored using Western blotting and assays of organ bath buffer. KEY RESULTS PVAT elicited an anticontractile effect in response to norepinephrine but not phenylephrine stimulation. In arteries surrounded by intact PVAT, the β3-adrenoceptor agonist, CL-316,243 reduced the vasoconstrictor effect of phenylephrine but not norepinephrine. Kv7 channel inhibition using XE 991 reversed the norepinephrine-induced anticontractile effect in exogenously applied PVAT studies. Adrenergic stimulation of PVAT with norepinephrine and CL-316,243, but not phenylephrine was associated with increased adipocyte-derived nitric oxide production and the contractile response to norepinephrine was augmented following incubation of exogenous PVAT with L-NMMA. PVAT from eNOS-/- mice had no anticontractile effect. Assays of adipocyte cAMP demonstrated an increase with norepinephrine stimulation implicating Gαs signalling in this process. CONCLUSIONS AND IMPLICATIONS We have shown that adipocyte-located β3-adrenoceptor stimulation leads to activation of Gαs signaling pathways with increased cAMP and the release of adipocyte-derived nitric oxide. This process is dependent upon Kv7 channel function. We conclude that adipocyte-derived nitric oxide plays a central role in anticontractile activity when rodent PVAT is stimulated by norepinephrine

Regional body composition as a determinant of arterial stiffness in the elderly. The Hoorn Study.

Regional body composition as a determinant of arterial stiffness in the elderly: The Hoorn Study. Snijder MB, Henry RM, Visser M, Dekker JM, Seidell JC, Ferreira I, Bouter LM, Yudkin JS, Westerhof N, Stehouwer CD. Institute for Research in Extramural Medicine, VU University Medical Center, Amsterdam, The Netherlands. [email protected] OBJECTIVE: To estimate the relation of precisely measured regional body composition with peripheral and central arterial stiffness in the elderly. METHODS: We investigated 648 participants (mean age 69.0 +/- 6.0 years) of the Hoorn Study, a population-based cohort study. Trunk fat, leg fat, trunk lean and leg lean mass were distinguished by dual-energy X-ray absorptiometry. We used ultrasound to measure the distensibility and compliance of the carotid, femoral and brachial arteries, and carotid Young's elastic modulus, as estimates of peripheral stiffness. As estimates of central stiffness we measured carotid-femoral transit time, aortic augmentation index and systemic arterial compliance. RESULTS: After adjustment for sex, age, height, mean arterial pressure, leg lean and leg fat mass, a larger trunk fat mass was consistently associated with higher peripheral arterial stiffness (standardized beta (beta) of mean Z-scores of all three large arteries -0.24, P < 0.001). In contrast, larger leg fat mass (beta = 0.15, P = 0.009) and leg lean mass (beta = 0.09, P = 0.20) were associated with lower peripheral arterial stiffness. Trunk or leg fat mass were not associated with central arterial stiffness. Leg lean mass, however, was consistently associated with lower central arterial stiffness (beta = 0.29, P < 0.001). CONCLUSIONS: Trunk fat mass may have adverse effects on peripheral, but not on central arterial stiffness, while leg fat was not harmful and may have a slight protective effect. Larger leg lean mass was the most important determinant of lower central arterial stiffness. These results provide a pathophysiological framework to explain not only the higher cardiovascular risk in individuals with larger trunk fat mass, but also the reduced cardiovascular risk in individuals with larger leg lean and fat mas

Human obesity and endothelium-dependent responsiveness

Obesity is an ongoing worldwide epidemic. Besides being a medical condition in itself, obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to stem from multiple abnormalities in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, disrupt vascular homeostasis by causing an imbalance between the NO pathway and the endothelin 1 system, with impaired insulin-stimulated endothelium-dependent vasodilation. Importantly, emerging evidence suggests that the vascular dysfunction of obesity is not just limited to the endothelium, but also involves the other layers of the vessel wall. In particular, obesity-related changes in medial smooth muscle cells seem to disrupt the physiological facilitatory action of insulin on the responsiveness to vasodilator stimuli, whereas the adventitia and perivascular fat appear to be a source of pro-inflammatory and vasoactive factors that may contribute to endothelial and smooth muscle cell dysfunction, and to the pathogenesis of vascular disease. While obesity-induced vascular dysfunction appears to be reversible, at least in part, with weight control strategies, these have not proved sufficient to prevent the metabolic and cardiovascular complication of obesity on a large scale. While a number of currently available drugs have shown potentially beneficial vascular effects in patients with obesity and the metabolic syndrome, elucidation of the pathophysiological mechanisms underlying vascular damage in obese patients is necessary to identify additional pharmacologic targets to prevent the cardiovascular complications of obesity, and their human and economic costs. LINKED ARTICLES: This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3

Social factors and obesity: an investigation of the role of health behaviours

OBJECTIVES: This study evaluated a behavioural model of the relation between social factors and obesity, in which differences in body mass index (BMI) across sociodemographic groups were hypothesized to be attributable to social group differences in health behaviours affecting energy expenditure (physical activity, diet and alcohol consumption and weight control). METHODS: A total of 8667 adults who participated in the 1995 Australian National Health and Nutrition Surveys provided data on a range of health factors including objectively measured height and weight, health behaviours, and social factors including family status, employment status, housing situation and migration status. RESULTS: Social factors remained significant predictors of BMI after controlling for all health behaviours. Neither social factors alone, nor health behaviours alone, adequately explained the variance in BMI. Gender-specific interactions were found between social factors and individual health behaviours. CONCLUSIONS: These results suggest that social factors moderate the relation between BMI and weight-related behaviours, and that the mechanisms underlying sociodemographic group differences in obesity may vary among men and women. Additional factors are likely to act in conjunction with current health behaviours to explain variation in obesity prevalence across sociodemographic groups.<br /

A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development

The allostatic load (AL) model represents an interdisciplinary approach to comprehensively conceptualize and quantify chronic stress in relation to pathologies throughout the life cycle. This article first reviews the AL model, followed by interactions among early adversity, genetics, environmental toxins, as well as distinctions among sex, gender, and sex hormones as integral antecedents of AL. We next explore perspectives on severe mental illness, dementia, and caregiving as unique human models of AL that merit future investigations in the field of developmental psychopathology. A complimenting transdisciplinary perspective is applied throughout, whereby we argue that the AL model goes beyond traditional stress–disease theories toward the advancement of person-centered research and practice that promote not only physical health but also mental healt

Randomized controlled trials - mechanistic studies of testosterone and the cardiovascular system

Testosterone deficiency is common in men with cardiovascular disease (CVD), and randomized placebo-controlled trials (RCTs) have reported beneficial effects of testosterone therapy on exercise-induced cardiac ischemia in chronic stable angina, functional exercise capacity, maximum oxygen consumption during exercise (VO ) and muscle strength in chronic heart failure (CHF), shortening of the Q-T interval, and improvement of some cardiovascular risk factors. Testosterone deficiency is associated with an adverse CV risk profile and mortality. Clinical and scientific studies have provided mechanistic evidence to support and explain the findings of the RCTs. Testosterone is a rapid-onset arterial vasodilator within the coronary circulation and other vascular beds including the pulmonary vasculature and can reduce the overall peripheral systemic vascular resistance. Evidence has demonstrated that testosterone mediates this effect on vascular reactivity through calcium channel blockade (L-calcium channel) and stimulates potassium channel opening by direct nongenomic mechanisms. Testosterone also stimulates repolarization of cardiac myocytes by stimulating the ultra-rapid potassium channel-operated current. Testosterone improves cardiac output, functional exercise capacity, VO and vagally mediated arterial baroreceptor cardiac reflex sensitivity in CHF, and other mechanisms. Independent of the benefit of testosterone on cardiac function, testosterone substitution may also increase skeletal muscle glucose metabolism and enhance muscular strength, both factors that could contribute to the improvement in functional exercise capacity may include improved glucose metabolism and muscle strength. Testosterone improves metabolic CV risk factors including body composition, insulin resistance, and hypercholesterolemia by improving both glucose utilization and lipid metabolism by a combination of genomic and nongenomic actions of glucose uptake and utilization expression of the insulin receptor, glucose transporters, and expression on regulatory enzymes of key metabolic pathways. The effect on high-density lipoprotein-cholesterol (HDL-C) differs between studies in that it has been found to fall, rise, or have no change in levels. Testosterone replacement can suppress the levels of circulating pro-inflammatory cytokines and stimulate the production of interleukin-10 (IL-10) which has anti-inflammatory and anti-atherogenic actions in men with CVD. No effect on C-reactive protein has been detected. No adverse effects on clotting factors have been detected. RCTs have not clearly demonstrated any significant evidence that testosterone improves or adversely affects the surrogate markers of atherosclerosis such as reduction in carotid intima thickness or coronary calcium deposition. Any effect of testosterone on prevention or amelioration of atherosclerosis is likely to occur over years as shown in statin therapy trials and not months as used in testosterone RCTs. The weight of evidence from long-term epidemiological studies supports a protective effect as evidenced by a reduction in major adverse CV events (MACEs) and mortality in studies which have treated men with testosterone deficiency. No RCT where testosterone has been replaced to the normal healthy range has reported a significant benefit or adverse effect on MACE nor has any recent meta-analysis