1,720,985 research outputs found
Visceral adipose tissue: Emerging role of gluco- and mineralocorticoid hormones in the setting of cardiometabolic alterations
No full textAbstract
Several clinical and experimental lines of evidence have highlighted the detrimental effects of visceral adipose tissue excess on cardiometabolic parameters. Besides, recent findings have shown the effects of gluco-and mineralocorticoid hormones on adipose tissue and have also underscored the interplay existing between such adrenal steroids and their respective receptors in the modulation of adipose tissue biology. While the fundamental role played by glucocorticoids on adipocyte differentiation and storage was already well known, the relevance of the mineralocorticoids in the physiology of the adipose organ is of recent acquisition. The local and systemic renin-angiotensin-aldosterone system (RAAS) acting on adipose tissue seems to contribute to the development of the cardiometabolic phenotype so that its modulation can have deep impact on human health. A better understanding of the pathophysiology of the adipose organ is of crucial importance in order to identify possible therapeutic approaches that can avoid the development of such cardiovascular and metabolic sequelae
Insulin receptors and renal sodium handling in hypertensive fructose-fed rats
No full textBackground. Insulin resistance and hypertension are present
in Sprague-Dawley rats fed a fructose-enriched diet. In these
rats, insulin might elevate blood pressure via an antinatriuretic
action.
Methods. To investigate the sodium-insulin interaction in
fructose-fed rats, we compared insulin sensitivity, insulin receptor
binding, and insulin receptor mRNA levels in the kidney
and skeletal muscle of rats that were fed standard rat chow or a
fructose-enriched diet (66%) with either low (0.07%), normal
(0.3%), or high (7.5%) NaCl concentrations for 3 weeks.
Results. Systolic blood pressure increased in the fructose-fed
rats receiving the normal and high-salt diet, but not the low-salt
diet.When the rats were fed the low-salt diet, the rate of glucose
infusion required to maintain euglycemia during a hyperinsulinemic
clamp and insulin receptor number and mRNA levels
in skeletal muscle were lower in fructose-fed than control rats.
High-salt diet decreased significantly the rate of glucose disposal
during the clamp and muscular insulin receptor number
and mRNA levels in control, but not fructose-fed rats. During
the low-salt diet, renal insulin receptor number and mRNA
levels were comparable in fructose-fed and control rats and hyperinsulinemia
had comparable acute antinatriuretic effects in
the two groups; when the rats were maintained on the high-salt
diet, the expected decrease in renal insulin receptor number
and mRNA levels occurred in control but not fructose-fed rats
and, consistent with this finding, the antinatriuretic response to
hyperinsulinemia was blunted only in controls. An inverse relationship
between dietary NaCl content and renal insulin receptor
mRNA levels was observed in control but not fructose-fed
rats.
Conclusion. Fructose-fed rats appear to have lost the feedback
mechanism that limits insulin-induced sodium retention
through a down-regulation of the renal insulin receptor when
the dietary NaCl content is increased. This abnormality might
possibly contribute to the elevation of blood pressure in these
rats
Bone health and aldosterone excess
No full textA picture of hyperparathyroidism secondary to increased urinary calcium excretion was found in 116 patients with primary aldosteronism (PA), compared with 110 essential hypertensives. After medical or surgical treatment in 40 PA patients, parathyroid hormone (PTH) levels were significantly reduced and bone mineral density (BMD) significantly increased at the lumbar spine, femoral neck, and total hip.
INTRODUCTION:
Recent studies have shown that aldosterone induces urinary calcium excretion leading to a reduction of calcemia with consequent secondary hyperparathyroidism and BMD loss. In patients with PA, this picture of hyperparathyroidism is significantly improved by treatment with adrenal surgery or with mineralocorticoid receptor antagonists. On these premises, the aim of the present study was to evaluate calcium and phosphate metabolism parameters in PA patients, compared with patients with essential hypertension (EH) and the effect of treatment of aldosterone excess on bone health in PA patients.
METHODS:
We studied 226 patients: 116 with PA (46 with an aldosterone-producing adenoma and 70 with bilateral adrenal hyperplasia) and 110 patients with EH. In 40 patients with PA, we evaluated biochemical parameters and bone mass, using the dual-energy X-ray absorptiometry, at baseline and after a mean follow-up of 24 months from treatment.
RESULTS:
In PA patients, compared with EH, PTH levels and urinary calcium excretion significantly increased while serum calcium significantly decreased with comparable vitamin D levels. At follow-up in PA patients, PTH levels were significantly reduced compared with basal evaluation, despite similar vitamin D amounts. At follow-up, we observed a significant improvement of the Z-score at the lumbar spine, femoral neck, and at total hip sites.
CONCLUSIONS:
Our results support previous data showing secondary hyperparathyroidism in PA patients, which is reversible after treatment. Moreover, this targeted treatment appears to be able to determine a significant improvement of BMD both at the spine and hip sites
Remote management of osteoporosis in the first wave of the COVID-19 pandemic
Full text linkSummary: We conducted a survey during the first pandemic wave of coronavirus disease 2019 (COVID-19) on a large group of osteoporotic patients to evaluate the general conditions of osteoporotic patients and the impact of the pandemic on the management of osteoporosis, finding high compliance to treatments and low COVID-19 lethality. Introduction: During the first pandemic wave of coronavirus disease 2019 (COVID-19), 209,254 cases were diagnosed in Italy; fatalities were 26,892 and were overwhelmingly older patients. The high prevalence of osteoporosis in this age group suggests a potential relationship between SARS-CoV-2 infection and bone metabolism. Methods: In a telephone survey conducted from April to May 2020, patients from the Osteoporosis Center, Clinic of Endocrinology and Metabolic Diseases of Umberto I Hospital (Ancona, Italy), were interviewed to evaluate the general clinical conditions of osteoporotic patients, compliance with osteoporosis medications, COVID-19 prevalence, hospitalization rate, COVID-19 mortality, and lethality. Results: Among the 892 patients interviewed, 77.9% were taking osteoporosis treatment and 94.6% vitamin D supplementation as prescribed at the last visit. COVID-19-like symptoms were reported by 5.1%, whereas confirmed cases were 1.2%. A total number of 33 patients had been in hospital and the hospitalization rate of those who had not discontinued vitamin D supplementation was less than 4%. There were eight deaths, two with a concomitant COVID-19 diagnosis. The prevalence of severe osteoporosis was 50% in total COVID-19 patients and 87.5% in deceased COVID-19 patients. The overall COVID-19 mortality was 0.2%; lethality was 20%, lower than the national rate of the same age group. Conclusions: This large group of osteoporotic patients showed high compliance and lower COVID-19 lethality compared to patients of the same age. Novel approaches such as telemedicine can provide critical support for the remote follow-up of patients with chronic diseases also in the setting of routine care
Aldosterone, mineralocorticoid receptor and the metabolic syndrome: role of the mineralocorticoid receptor antagonists
No full textSeveral lines of evidence suggest a detrimental effect of aldosterone excess on the development of metabolic alterations. Glucose metabolism derangements due to aldosterone action are frequently observed not only in patients with primary aldosteronism but also in patients with obesity. A contribution to the hyperaldosteronism observed in obese subjects can be attributed, at least in part, to the action of still unidentified adipocyte-derived factor. Aldosterone, through genomic and non-genomic actions contributes to induce several abnormalities: pancreatic fibrosis, impaired beta cell function, as well as reduced skeletal muscle and adipose tissue insulin sensitivity. Oxidative stress, systemic inflammation, together with these metabolic alterations may explain the appearance of the cardiometabolic syndrome and the progression of cardiovascular and renal diseases, in the presence of inappropriate aldosterone levels. The biological actions of aldosterone are mediated by mineralocorticoid receptor (MR), although MR can be activated through an aldosterone independent fashion. Besides salt-water homeostasis, MR activation promotes inflammation, endothelial dysfunction, cardiovascular remodelling and affects adipose tissue differentiation and function. Clinical and experimental studies have shown that MR blockade is able to suppress inflammation, to improve endothelium- dependent vasorelaxation, but most interestingly, to improve pancreatic insulin release as well as insulin-mediated glucose utilization. These actions indicate MR antagonists as a useful therapeutic tool able not only to reduce cardiovascular risk and renal damage, but also to improve metabolic sequaelae
Evolution of computed tomography-detectable adrenal nodules in patients with bilateral primary aldosteronism
Full text linkIdiopathic hyperaldosteronism due to bilateral autonomous production of aldosterone is the most common subtype of primary hyperaldosteronism and is diagnosed by adrenal venous sampling. The aim of our study was to assess the over time evolution of computed tomography (CT)-detectable adrenal nodule(s) in patients with idiopathic hyperaldosteronism. Thirty-two patients (23 males and 9 females; age 50±9 years) diagnosed as bilateral PA and having nodular adrenal lesions (median diameter 12 mm, range 8 to 28 mm; 28 unilateral and 4 bilateral), were studied. Adrenal was described as nodular when unilateral or bilateral nodule(s) of at least 8 mm in diameter were detected using CT with contrast and fine cuts. The diagnosis of a benign adrenal nodule rested on the following CT criteria: size <4 cm, regular shape with well-defined margins, homogeneous and hypodense content. All patients had CT imaging re-evaluated 3 to 6 years (median 45 months) after diagnosis. A unilateral nodular lesion enlargement ≥25% was detected in 2 cases; a slight increase (<25%) or no variations or a decrease of nodule size occurred in the remaining 30 cases. No patients showed appearance of radiological picture of malignancy or new masses in the ipsilateral/contralateral glands. At follow-up all patients reported compliance to medications, and 29/32 patients had a persistent clinical/biochemical control of the disease. Three patients showed hypertension resistant to a combination of four different antihypertensive drugs. Over time CT variations of adrenal nodules are uncommon and without apparent signs of malignancy in patients with AVS-confirmed bilateral PA. A diagnosti
Primary aldosteronism and essential hypertension: assessment of cardiovascular risk at diagnosis and after treatment.
No full textPrimary aldosteronism (PA), the most frequent form of secondary hypertension, is characterized by a higher rate of cardiovascular (CV) events than essential hypertension (EH). Aim of the study was to evaluate the cardiovascular risk according to the ESH/ESC 2007 guidelines, in patients with PA and with EH, at diagnosis and after treatment.
METHODS AND RESULTS:
We prospectively studied 102 PA patients (40 with aldosterone producing adenoma-APA and 62 with idiopathic hyperaldosteronism-IHA) and 132 essential hypertensives at basal and after surgical or medical treatment (mean follow-up period 44 months for PA and 42 months for EH). At baseline evaluation the stratification of CV risk was significantly different: the predominant risk category was the high CV risk (50% in total PA, 53% in PA matched for blood pressure values and 55% in EH), but the very high risk category was twice in PA than in EH patients (36% in total PA and 33% in matched PA vs. 17% in EH, p < 0.05). The worse risk profile of PA was due to a higher prevalence of glycemic alterations, metabolic syndrome and left ventricular hypertrophy (LVH) (p < 0.05). After adequate treatment, the CV risk was significantly reduced becoming comparable in PA and in EH patient due to a reduction of hypertension grading, prevalence of metabolic syndrome, hypertension persistence and LVH (p < 0.05).
CONCLUSION:
Patients with PA present a high CV risk, which is in part reversible after specific treatment, due both to the reduced blood pressure values and to the improvement of end-organ damage
Vitamin D levels and bone mineral density: are LH levels involved in the pathogenesis of bone impairment ih hypogonadal men?
No full textThe Effects of Polyphenols on Bone Metabolism in Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Control Trials
Full text linkOsteoporosis is a condition favored by the postmenopausal decline in estrogen levels and worsened by oxidative stress (OS). Polyphenols are natural compounds abundantly found in fruits and vegetables, and they exert antioxidant and hormonal effects that could be useful in osteoporosis prevention, as suggested by epidemiological studies showing a lower incidence of fractures in individuals consuming polyphenol-rich diets. The aim of our meta-analysis is to evaluate the effects of polyphenols on bone mineral density (BMD, primary endpoint) and bone turnover markers (BTMs, secondary endpoint) in postmenopausal women. Twenty-one randomized control trials (RCTs) were included in our analysis after in-depth search on PubMed, EMBASE, and Scopus databases. We found that supplementation with polyphenols for 3-36 months exerted no statically significant effects on BMD measured at lumbar spine (sMD: 0.21, 95% CI [-0.08 to 0.51], p = 0.16), femoral neck (sMD: 0.16, 95% CI [-0.23 to 0.55], p = 0.42), total hip (sMD: 0.05, 95% CI [-0.14 to 0.24], p = 0.61), and whole body (sMD: -0.12, 95% CI [-0.42 to 0.17], p = 0.41). Subgroup analysis based on treatment duration showed no statistical significance, but a significant effect on lumbar BMD emerged when studies with duration of 24 months or greater were analyzed separately. On the other hand, we found a significantly slight increase in bone-specific alkaline phosphatase (BALP) levels (sMD: 1.27, 95% CI [1.13 to 1.42], p < 0.0001) and a decrease in pyridinoline (PD) levels (sMD: -0.58, 95% CI [-0.77 to -0.39], p < 0.0001). High heterogeneity among studies and unclear risk of bias in one third of the included studies emerged. A subgroup analysis showed similar effects for different duration of treatment and models of dual-energy X-ray absorptiometry (DXA) scanner. More robust evidence is needed before recommending the prescription of polyphenols in clinical practice
Cellular mechanisms of insulin resistance in rats with fructose-induced hypertension
No full textBackground: Feeding a high-fructose diet induces
hypertension and insulin-resistance in Sprague-Dawley
rats.
Methods: To investigate whether insulin receptors contribute
to abnormal glucose metabolism and whether their
regulation is differentially regulated in different tissues, we
evaluated the glycemic and insulinemic response to an oral
glucose load, insulin receptor binding, and insulin receptor
messengerRNA (mRNA) levels in tissues of rats that were
fed either standard rat chow or a diet containing 66%
fructose for 2 weeks.
Results: Blood pressure and plasma triglycerides increased
significantly in the fructose-fed rats, whereas body
weight, fasting plasma glucose, and plasma insulin did not
differ significantly from controls. Plasma glucose and insulin
responses to oral glucose were significantly greater
in fructose-fed than in control rats. Insulin receptor-binding
characteristics were determined by an in situ autoradiographic
technique associated with computerized
microdensitometry. The insulin receptor number was significantly
lower in both skeletal muscle and liver of fructose-
fed rats as compared to controls, whereas no
difference was observed in the kidney. No significant
differences were found in binding affinity. Insulin receptor
mRNA levels were determined by slot-blot hybridization
with a cRNA probe encoding the 5 end of the rat insulin
receptor cDNA. Consistent with binding data, mRNA levels
were significantly lower in skeletal muscle and liver of
fructose-fed rats as compared to controls, but not in the
kidney.
Conclusions: Decreased number of insulin receptors
occurring at the level of gene expression is present in
skeletal muscle and liver of fructose-fed rats and might
contribute to insulin resistance in this model
- …
