Elevated Plasma Levels of Growth Arrest Specific 6 (Gas6) Protein in Severe Obesity: Implications for Adipose Tissue and Inflammation.

BACKGROUND Preliminary data suggest an adipogenic role for growth arrest-specific 6 (Gas6), a pleiotropic molecule involved in inflammation, proliferation, and hemostasis through its Tyro3, Axl, and MerTK (TAM) receptors. This study compares Gas6 expression in plasma and visceral and subcutaneous adipose tissue in 42 adults with obesity (body mass index ≥40 kg/m²) and 32 normal-weight controls to elucidate its role in obesity and related metabolic alterations. MATERIAL AND METHODS Using a case-control design, we measured Gas6 levels in plasma via a validated sandwich enzyme-linked immunosorbent assay and in adipose tissues through quantitative polymerase chain reactio with specific probes. Medians and correlations were analyzed using Mann-Whitney and Spearman tests. A general linear model assessed the impact of covariates on the Gas6-anthropometric relationship, with statistical significance determined by P values. RESULTS Plasma Gas6 levels were significantly higher in the obese group than in controls (P=0.0006). While Gas6 mRNA expression did not significantly differ in subcutaneous adipose tissue between groups, it was notably higher in visceral than subcutaneous adipose tissue in controls (P<0.05). A significant correlation was found between plasma Gas6 levels and body mass index (P=0.001). CONCLUSIONS Gas6 plasma levels are elevated in morbid obesity, particularly in visceral adipose tissue, and are linked to altered glucose tolerance in female patients. These findings highlight the role of Gas6 in obesity-related metabolic complications and suggest avenues for further research and potential therapies.

Source and amount of carbohydrate in the diet and inflammation in women with polycystic ovary syndrome.

High carbohydrate intake and low-grade inflammation cooperate with insulin resistance and hyperandrogenism to constitute an interactive continuum acting on the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age characterised by oligo-anovulatory infertility and cardiometabolic disorders. The role of insulin in PCOS is pivotal both in regulating the activity of ovarian and liver enzymes, respectively involved in androgen production and in triggering low-grade inflammation usually reported to be associated with an insulin resistance, dyslipidaemia and cardiometabolic diseases. Although an acute hyperglycaemia induced by oral glucose loading may increase inflammation and oxidative stress by generating reactive oxygen species through different mechanisms, the postprandial glucose increment, commonly associated with the Western diet, represents the major contributor of chronic sustained hyperglycaemia and pro-inflammatory state. Together with hyperinsulinaemia, hyperandrogenism and low-grade inflammation, unhealthy diet should be viewed as a key component of the 'deadly quartet' of metabolic risk factors associated with PCOS pathophysiology. The identification of a tight diet-inflammation-health association makes the adoption of healthy nutritional approaches a primary preventive and therapeutic tool in women with PCOS, weakening insulin resistance and eventually promoting improvements of reproductive life and endocrine outcomes. The intriguing nutritional-endocrine connections operating in PCOS underline the role of expert nutritionists in the management of this syndrome. The aim of the present review is to provide an at-a-glance overview of the possible bi-directional mechanisms linking inflammation, androgen excess and carbohydrate intake in women with PCOS.

Vitamin D and Neurological Diseases: An Endocrine View.

Vitamin D system comprises hormone precursors, active metabolites, carriers, enzymes, and receptors involved in genomic and non-genomic effects. In addition to classical bone-related effects, this system has also been shown to activate multiple molecular mediators and elicit many physiological functions. In vitro and in vivo studies have, in fact, increasingly focused on the "non-calcemic" actions of vitamin D, which are associated with the maintenance of glucose homeostasis, cardiovascular morbidity, autoimmunity, inflammation, and cancer. In parallel, growing evidence has recognized that a multimodal association links vitamin D system to brain development, functions and diseases. With vitamin D deficiency reaching epidemic proportions worldwide, there is now concern that optimal levels of vitamin D in the bloodstream are also necessary to preserve the neurological development and protect the adult brain. The aim of this review is to highlight the relationship between vitamin D and neurological diseases.

Altered glucose metabolism rather than naive type 2 diabetes mellitus (T2DM) is related to vitamin D status in severe obesity.

CONTEXT: The last decades have provided insights into vitamin D physiology linked to glucose homeostasis. Uncertainties remain in obesity due to its intrinsic effects on vitamin D and glucose tolerance. OBJECTIVES: To assess the relationship between vitamin D and glucose abnormalities in severely obese individuals previously unknown to suffer from abnormal glucose metabolism. SETTING: Tertiary care centre. PATIENTS: 524 obese patients (50.3 ± 14.9 yrs; BMI, 47.7 ± 7.3 kg/m2) screened by OGTT, HbA1c and the lipid profile. Vitamin D status was assessed by 25(OH)D3, PTH and electrolyte levels. 25(OH)D3 deficiency/insufficiency were set at 20 and 30 ng/ml, respectively. All comparative and regression analyses were controlled for age, BMI and gender. RESULTS: The prevalence of vitamin D deficiency/insufficiency and secondary hyperparathyroidism were 95% and 50.8%, respectively. Normal glucose tolerance (NGT), impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) were found in 37.8%, 40.5% and 21.7% of cases, respectively. Large variations in metabolic parameters were seen across categories of vitamin D status, but the only significant differences were found for C-peptide, tryglicerides, LDL- and HDL-cholesterol levels (p < 0.05 for all). The prevalence of vitamin D deficiency was documented to be slightly but significantly more frequent in glucose-intolerant patients (IFG + IGT + T2DM) compared to the -normotolerant counterpart (87% vs. 80%, p < 0.05). In partial correlation analyses, there was no association between vitamin D levels and glucose-related markers but for HbA1c (r = -0.091, p < 0.05), and both basal and OGTT-stimulated insulin levels (r = 0.097 and r = 0.099; p < 0.05 for all). Vitamin D levels were also correlated to HDL-cholesterol (r = 0.13, p = 0.002). Multivariate regression analysis inclusive of vitamin D, age, BMI, gender and fat mass as independent variables, showed that vitamin D was capable of predicting HbA1c levels (ß = -0.101, p < 0.05). CONCLUSIONS: Given the inherent effect of obesity on vitamin D and glucose homeostasis, current data suggest a potential independent role for vitamin D in the regulation of glucose metabolism in a setting of obese patients previously unknown to harbour glucose metabolism abnormalities.

Differential patterns of regional neuroadrenergic cardiovascular drive in acromegalic disease.

It has been shown that acromegaly is characterized by an autonomic imbalance and by marked sympathoinhibition. However, there is no information available as to whether adrenergic inhibition is confined to selected vascular districts or, rather, is generalized. We examined 17 newly diagnosed active acromegalic patients without hyperprolactinaemia, pituitary hormone deficiencies, obstructive sleep apnoea and cardiac hypertrophy and 14 healthy subjects matched for age, sex and body mass index. For each subject, we collected information regarding anthropometric parameters and echocardiography, and collected plasma samples to investigate anterior pituitary function, glucose and lipid metabolism and plasma leptin levels. Beat-to-beat mean arterial pressure, heart rate and efferent post-ganglionic muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively; determined by microneurography) were measured. Both MSNA and SSNA were recorded in a randomized sequence over two 30 min periods. Measurements also included evaluation of SSNA responses to emotional stimulus. In addition to significant reductions in plasma leptin levels, acromegalic patients had markedly decreased MSNA compared with the healthy controls. There were no significant differences in SSNA between the two groups, either under basal conditions or in responses to arousal stimuli. There was a significant and direct correlation between MSNA and plasma leptin levels, but not between plasma leptin and SSNA. These data provide the first evidence that the sympathetic inhibition characterizing the early phase of acromegaly is not generalized to the entire cardiovascular system.

The perception of affective touch in women affected by obesity.

Introduction: Pleasant and comforting bodily contacts characterized intimate and affective interactions. Affective touch informs us about others' emotions and intentions, sustains intimacy and closeness, protecting from loneliness and psychological distress. Previous evidence points to an altered experience of affective touch in clinical populations reporting interpersonal difficulties. However, there is no investigation of affective touch in obesity, which is often associated with negative affective-relational experiences since childhood. Methods: This study aimed to provide the first evidence about the experience of affective touch in obesity by comparing 14 women with obesity with 14 women with healthy weight. Participants rated the pleasantness of both imagined and actual tactile stimuli, which consisted of (i) soft-brush strokes, (ii) touches of the experimenter's hand, and (iii) of a plastic stick (as control, non-affective, stimulation). Participants should report the pleasantness of each kind of touch. Moreover, we explored lifespan experiences of affective touch and interpersonal pleasure in social contexts through self-report questionnaires. Results: No differences emerged for the pleasantness of affective touch (in both the real and imagery task) between the two groups. However, participants with obesity reported less frequent and less satisfying early experiences of affective touch when compared with the controls. Discussion: Our results spoke in favor of a preserved experience of affective touch when experimentally probed in obesity, despite a limited early exposure to bodily affective contacts. We interpreted our results in the light of the social reconnection hypothesis. Nevertheless, we provided crucial methodological considerations for future research, considering that both the experimenter's and the brush touch may not resemble adequately real-life experiences, in which affective touch involves intimate people.

Comparative efficacy of three Bayesian variable selection methods in the context of weight loss in obese women.

The use of high-dimensional data has expanded in many fields, including in clinical research, thus making variable selection methods increasingly important compared to traditional statistical approaches. The work aims to compare the performance of three supervised Bayesian variable selection methods to detect the most important predictors among a high-dimensional set of variables and to provide useful and practical guidelines of their use. We assessed the variable selection ability of: (1) Bayesian Kernel Machine Regression (BKMR), (2) Bayesian Semiparametric Regression (BSR), and (3) Bayesian Least Absolute Shrinkage and Selection Operator (BLASSO) regression on simulated data of different dimensions and under three scenarios with disparate predictor-response relationships and correlations among predictors. This is the first study describing when one model should be preferred over the others and when methods achieve comparable results. BKMR outperformed all other models with small synthetic datasets. BSR was strongly dependent on the choice of its own intrinsic parameter, but its performance was comparable to BKMR with large datasets. BLASSO should be preferred only when it is reasonable to hypothesise the absence of synergies between predictors and the presence of monotonous predictor-outcome relationships. Finally, we applied the models to a real case study and assessed the relationships among anthropometric, biochemical, metabolic, cardiovascular, and inflammatory variables with weight loss in 755 hospitalised obese women from the Follow Up OBese patients at AUXOlogico institute (FUOBAUXO) cohort.

Impact of 4-week of a restricted Mediterranean diet on taste perception, anthropometric, and blood parameters in subjects with severe obesity.

Introduction: The study of taste functionality and its relation to human health is receiving growing attention. Obesity has been reported to cause alterations in sensory perception regarding system functionality and preferences. However, a small body of research addresses tastes perception and its modification with the achievement of body mass reduction through surgical intervention. Much fewer efforts have been made to evaluate the impact of mild restrictive nutritional intervention on gustatory functions. Thus, the objectives of this study were to determine if a dietary intervention of 4 weeks following a restricted balanced Mediterranean diet would affect the sweet and salty taste thresholds of subjects with severe obesity and could influence their anthropometric and blood parameters. Methods: Fifty-one patients with severe obesity (F: 31; age: 43.7 ± 12.5; BMI = 47.6 ± 1.0) were enrolled in the study. The recognition threshold for sweet and salty taste and anthropometric and blood parameters were assessed before and after the 4-week weight loss program. Results and Discussion: The Mediterranean diet has proven to be an effective treatment, significantly improving all anthropometric and blood parameters (p < 0.05) after 4 weeks of intervention. Moreover, the hypo-sodium treatment associated with the diet significantly improved the salty threshold (p < 0.001). No changes were detected for the sweet threshold. Collectively, these data highlight that dietary treatment might impact taste perception differently. Therefore, a taste-oriented nutritional intervention could represent a novel approach to developing more individualized, taste-oriented follow-up interventions to maintain sustainable and long-term weight loss.

Development of a questionnaire on nutritional knowledge for the obese hospitalized patient: the NUTRIKOB questionnaire.

Introduction: Different approaches, involving different areas and figures, are useful for the rehabilitation of obese subjects through a multidisciplinary hospital path. A focal point of rehabilitation is represented by education on healthy eating by increasing the dietary knowledge patients. Few tools investigating food knowledge are available in Italy: therefore, the need has emerged to develop easy-to-use tools for clinical practice that allow to detect food knowledge to set up a more targeted food re-education. The following work aimed at building and validating a questionnaire capable of investigating the dietary knowledge of the population affected by obesity. Methods: A pool of experts carried out a review of the literature, gathering all the information necessary to select and construct the best set of questions and the format of the final project of the questionnaire. During statistical analysis the validity, reproducibility and stability of the questionnaire were investigate in a sample of 450 subjects with obesity. Results: Early analysis disclosed that 5 questions of the original questionnaire had no discriminating power. The successive validation phases were successful, confirming good content validity, stability and reproducibility over time. Discussion: The questionnaire has all the characteristics to be considered a valid tool for investigating dietary knowledge in the obese population. The psychometric tests confirmed a good internal consistency of the structure, a validity of the content, a good reproducibility and stability over time.

Postprandial triglyceride profile after a standardized oral fat load is altered in growth hormone (GH)-deficient adult patients and is not improved after short-term GH replacement therapy.

OBJECTIVE: Adult growth hormone deficiency (GHD) has detrimental effects on metabolic profile, leading to an increased cardiovascular mortality and morbidity. Above all, disturbance in postprandial triglyceride metabolism is of major concern because of the crucial role of triglyceride-rich lipoproteins in atherogenesis. The majority of previous studies on GH replacement have shown favourable changes in the fasting lipid profile. Aim of this study is to investigate whether this beneficial effect is exerted also on postprandial triglyceride (TG) metabolism. PATIENTS AND METHODS: We challenged nine GHD patients with a standardized fat loading meal at baseline and after 6 months of GH replacement therapy. Nine healthy control subjects were similarly tested under baseline conditions. Blood samples were obtained before and up to 8 h after fat loading for serum lipid analysis. RESULTS: We found that GHD patients with fasting TG level in the normal range (1·29 ± 0·31 mm) had a delayed postprandial TG clearance compared to healthy controls (triglyceride level at 8 h, 3·82 ± 0·83 vs 1 ± 0·06 mm P < 0·01), and the postprandial hypertriglyceridaemia was not corrected by 6 months of GH therapy. CONCLUSIONS: This study has shown for the first time that GHD adult patients have a higher postprandial triglyceridaemia compared to healthy controls when challenged by a standardized fat load and that this atherogenic feature is not normalized by short-term GH treatment despite a decrease in visceral fat mass described during the replacement therapy.

Clinical relevance of cardiac structure and function abnormalities in patients with Cushing's syndrome before and after cure.

OBJECTIVES: Sustained hypercortisolism impacts cardiac function, and, indeed, cardiac disease is one of the major determinants of mortality in patients with Cushing's syndrome. The aim of this study was to assess the clinical relevance of cardiac structure and function alterations by echocardiography in patients with active Cushing's syndrome and after disease remission. STUDY DESIGN: Seventy-one patients (61 women, 10 men) with Cushing's syndrome and 70 age-, sex- and blood pressure-matched controls were enrolled. Echocardiography was performed in 49 patients with active disease and at several time points after remission in 44 patients (median follow-up 46.4 months), and prevalence of abnormal left ventricular mass measurements and systolic and diastolic functions indices was compared between patients with active disease, after remission and controls. Twenty-two patients were evaluated both before and after remission. RESULTS: Up to 70% of patients with active Cushing's syndrome presented abnormal left ventricular mass parameters; 42% presented concentric hypertrophy and 23% concentric remodelling. Major indices of systolic and diastolic functions, i.e. ejection fraction and E/A ratio, respectively, were normal. Upon remission of hypercortisolism, left ventricular mass parameters ameliorated considerably, although abnormal values were still more frequent than in controls. Both cortisol excess and hypertension contribute to cardiac mass alterations and increase the prevalence of target organ damage. CONCLUSIONS: Cushing's syndrome is associated with an increased risk for abnormalities of cardiac mass, which ameliorates, but does not fully disappear after remission. Systolic and diastolic functions are largely within the normal range in these patients.

Does physical weight alter the mental representation of the body? Evidence from motor imagery in obesity.

Obesity is a clinical condition that impacts severely the physical body. However, evidence related to the mental representation of the body in action is scarce. The few available studies only focus on avoiding obstacles, rather than participants imagining their own body. To advance knowledge in this field, we assessed the performance of 22 individuals with obesity compared with 30 individuals with a healthy weight in two tasks that implied different motor (more implicit vs. more explicit) imagery strategies. Two tasks were also administered to control for visual imagery skills, to rule out confounding factors. Moreover, we measured body uneasiness, through a standard questionnaire, as body image negativity could impact on other body representation components. Our findings do not show differences in the motor imagery tasks between individuals with obesity and individuals with healthy weight. On the other hand, some differences emerge in visual imagery skills. Crucially, individuals with obesity did report a higher level of body uneasiness. Despite a negative body image and visual imagery differences, obesity per se does not impact on the representation of the body in action. Importantly, this result is independent from the level of awareness required to access the mental representation of the body.

Behavioural evidence of altered sensory attenuation in obesity.

Body ownership (i.e., the conscious belief of owning a body) and sense of agency (i.e., being the agent of one's own movements) are part of a pre-reflective experience of bodily self, which grounds on low-level complex sensory-motor processes. Although previous literature had already investigated body ownership in obesity, sense of agency was never explored. Here, we exploited the sensory attenuation effect (i.e., an implicit marker of the sense of agency; SA effect) to investigate whether the sense of agency was altered in a sample of 18 individuals affected by obesity as compared with 18 healthy-weight individuals. In our experiment, participants were asked to rate the perceived intensity of self-generated and other-generated tactile stimuli. Healthy-weight individuals showed a significantly greater SA effect than participants affected by obesity. Indeed, while healthy-weight participants perceived self-generated stimuli as significantly less intense as compared to externally generated ones, this difference between stimuli was not reported by affected participants. Our results relative to the SA effect pinpointed an altered sense of agency in obesity. We discussed this finding within the motor control framework with reference to obesity. We encouraged future research to further explore such effect and its role in shaping the clinical features of obesity.

The pattern of TSH and fT4 levels across different BMI ranges in a large cohort of euthyroid patients with obesity.

Purpose: A multifold association relates the hypothalamo-pituitary-thyroid axis to body weight. The potential underlying mechanisms are incompletely understood. Further, the mild severity of obesity and the small proportion of individuals with obesity in so far published cohort studies provide little insights on metabolic correlates of thyroid function in obesity. Methods: We retrospectively enrolled 5009 adults with obesity (F/M, 3448/1561; age range, 18-87 years; BMI range, 30.0-82.7 kg/m2), without known thyroid disease in a study on TSH and fT4 levels, lipid profile, glucose homeostasis and insulin resistance, anthropometric parameters including BIA-derived fat mass (%FM) and fat-free mass (FFM). Results: The overall reference interval for TSH in our obese cohort was 0.58-5.07 mIU/L. As subgroups, females and non-smokers showed higher TSH levels as compared to their counterparts (p<0.0001 for both), while fT4 values were comparable between groups. There was a significant upward trend for TSH levels across incremental BMI classes in females, while the opposite trend was seen for fT4 levels in males (p<0.0001 for both). Expectedly, TSH was associated with %FM and FFM (p<0,0001 for both). TSH and fT4 showed correlations with several metabolic variables, and both declined with aging (TSH, p<0.0001; fT4, p<0.01). In a subgroup undergoing leptin measurement, leptin levels were positively associated with TSH levels (p<0.01). At the multivariable regression analysis, in the group as a whole, smoking habit emerged as the main independent predictor of TSH (ß=-0.24, p<0.0001) and fT4 (ß=-0.25, p<0.0001) levels. In non-smokers, %FM (ß=0.08, p<0.0001) and age (ß=-0.05, p<0.001) were the main significant predictors of TSH levels. In the subset of nonsmokers having leptin measured, leptin emerged as the strongest predictor of TSH levels (ß=0.17, p<0.01). Conclusions: Our study provides evidence of a gender- and smoking-dependent regulation of TSH levels in obesity.

Circulating Irisin in Children and Adolescents With Prader-Willi Syndrome: Relation With Glucose Metabolism.

Irisin is a myokine involved in the browning of white adipose tissue and regulation of energy expenditure, glucose homeostasis and insulin sensitivity. Debated evidence exists on the metabolic role played by irisin in children with overweight or obesity, while few information exist in children with Prader Willi Syndrome (PWS), a condition genetically prone to obesity. Here we assessed serum irisin in relation to the metabolic profile and body composition in children and adolescents with and without PWS. In 25 PWS subjects [age 6.6-17.8y; body mass index standard deviation score (BMI SDS) 2.5 ± 0.3] and 25 age, and BMI-matched controls (age 6.8-18.0y; BMI SDS, 2.8 ± 0.1) we assessed irisin levels and metabolic profile inclusive of oral glucose tolerance test (OGTT), and body composition by dual-energy X-ray absorptiometry (DXA). In PWS, we recorded lower levels of fat-free mass (FFM) (p <0.05), fasting (p<0.0001) and 2h post-OGTT insulin (p<0.05) and lower insulin resistance as expressed by homeostatic model of insulin resistance (HOMA-IR) (p<0.0001). Irisin levels were significantly lower in PWS group than in controls with common obesity (p<0.05). In univariate correlation analysis, positive associations linked irisin to insulin OGTT0 (p<0.05), insulin OGTT120 (p<0.005), HOMA-IR (p<0.05) and fasting C-peptide (p<0.05). In stepwise multivariable regression analysis, irisin levels were independently predicted by insulin OGTT120. These results suggest a link between irisin levels and insulin sensitivity in two divergent models of obesity.

Gut Microbiota and Fear Processing in Women Affected by Obesity: An Exploratory Pilot Study.

The microbiota-gut-brain axis extends beyond visceral perception, influencing higher-order brain structures, and ultimately psychological functions, such as fear processing. In this exploratory pilot study, we attempted to provide novel experimental evidence of a relationship between gut microbiota composition and diversity, and fear-processing in obesity, through a behavioral approach. Women affected by obesity were enrolled and profiled for gut microbiota, through 16S rRNA amplicon sequencing. Moreover, we tested their ability to recognize facial fearful expressions through an implicit-facial-emotion-recognition task. Finally, a traditional self-report questionnaire was used to assess their temperamental traits. The participants exhibited an unbalanced gut microbiota profile, along with impaired recognition of fearful expressions. Interestingly, dysbiosis was more severe in those participants with altered behavioral performance, with a decrease in typically health-associated microbes, and an increase in the potential pathobiont, Collinsella. Moreover, Collinsella was related to a lower expression of the persistence temperamental trait, while a higher expression of the harm-avoidance temperament, related to fear-driven anxiety symptoms, was linked to Lactobacillus. Once confirmed, our findings could pave the way for the design of innovative microbiome-based strategies for the treatment of psychological and emotional difficulties by mitigating obesity-related consequences and behaviors.

Psychological complications in patients with acromegaly: relationships with sex, arthropathy, and quality of life.

PURPOSE: Current treatment of acromegaly restores a normal life expectancy in most cases. So, the study of persistent complications affecting patients' quality of life (QoL) is of paramount importance, especially motor disability and depression. In a large cohort of acromegalic patients we aimed at establishing the prevalence of depression, to look for clinical and sociodemographic factors associated with it, and to investigate the respective roles (and interactions) of depression and arthropathy in influencing QoL. METHODS: One hundred and seventy-one acromegalic patients (95 women and 76 men, aged 20-85 years) among those recruited in a cross-sectional Italian multicentric study were investigated. Each patient filled in three validated questionnaires: AcroQoL, WOMAC (measuring articular pain, stiffness and functionality), and AIMS (evaluating articular symptoms and depression). RESULTS: A very high (up to 28%) depression rate was detected in acromegalic subjects. Two patients showing pathological AIMS depression scores, committed suicide during the three years observational period. In our population poor psychological status was significantly associated with female sex. Furthermore, a significant strong correlation was found between AIMS depression score and WOMAC score. Both depression and arthropathy-related motor disability turned out to independently contribute with similar strength to the impairment of QoL. CONCLUSIONS: We report a high prevalence of depression in acromegaly, which is associated with female sex and arthropathy. Both depression and arthropathy strongly and independently contribute to the impaired QoL of patients. Our study shows that assessment and monitoring of psychological status is mandatory in acromegaly, also suggesting an inexpensive tool for this assessment.

Von Willebrand factor and fibrinolytic parameters during the desmopressin test in patients with Cushing's disease.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Desmopressin is a known haemostatic agent and is also being used, albeit at lower doses, during the diagnostic work-up of Cushing's syndrome, a condition characterized by excess cortisol concentrations and frequent thromboembolic events. No study has yet evaluated whether administration of desmopressin for diagnostic purposes induces significant, adverse changes in endothelial cell markers in these patients. WHAT THIS STUDY ADDS: Administration of desmopressin to patients with Cushing's disease induces changes in endothelial cell markers comparable with those observed in obese and normal weight subjects. It follows, that desmopressin testing does not induce disease-specific untoward changes in coagulatory markers in patients with endogenous hypercortisolism and its use in this context appears safe. AIMS: Desmopressin, a vasopressin analogue, is used for various clinical purposes, including haemostasis and, in recent times, the diagnostic work-up of patients with Cushing's syndrome, a condition associated with a known prothrombotic profile. We decided to evaluate whether and to what extent a diagnostic dose of desmopressin induces significant changes in endothelial parameters in patients with Cushing's disease (CD) and obese and normal weight controls. METHODS: Twelve patients with CD, 10 obese and five normal weight controls were studied. Von Willebrand antigen (VWF:Ag), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured at baseline and up to 4 h after 10 µg desmopressin i.v. RESULTS: Desmopressin 10 µg transiently increased VWF:Ag and t-PA and decreased PAI-1 in all subjects. The magnitude of the VWF:Ag and t-PA increases after desmopressin was comparable in the three groups (VWF:Ag peak-to-basal ratio 1.9 ± 0.17, 1.5 ± 0.11 and 1.8 ± 0.13 and t-PA peak-to-basal ratio 1.6 ± 0.18, 1.6 ± 0.20 and 1.8 ± 0.24 for CD, obese and controls, respectively, all NS). The PAI-1 decrease observed in patients with CD was comparable with obese (0.7 ± 0.07 and 0.6 ± 0.09, NS) and controls (0.7 ± 0.07 vs. 0.4 ± 0.09, P= 0.08). CONCLUSIONS: Administration of desmopressin to patients with CD for diagnostic purposes induces a transitory increase in VWF:Ag counterbalanced by a decrease in PAI-1 and increase in t-PA. The magnitude of these changes is largely comparable with that observed in obese and normal weight controls. Our data show that testing with desmopressin does not induce disease-specific changes in endothelial markers in patients with CD.

The self-perceived body size in obesity: Evidence from the implicit representation of the hand.

To locate our body in the space, we rely on an implicit representation of body size and shape: the body model. Evidence about the implicit representation of bodily dimensions in obesity is rare. Nevertheless, it seems to suggest that such representation is not altered in obesity compared to healthy weight individuals. To probe further this hypothesis, we investigated the implicit representation of hand dimensions with a landmark localisation task, comparing individuals with obesity and healthy weight individuals. Furthermore, as body model distortions may be related to tactile acuity, the tactile acuity threshold was measured using a two-point discrimination task. In accordance with the previous evidence, we observed that healthy weight participants showed a significant underestimation of finger length and overestimation of hand width. Interestingly, comparable body model distortions were shown also in participants with obesity. No differences in tactile acuity emerged between the two groups; also, when considering the whole sample, as tactile acuity decreases hand width overestimation increases. Thus, obesity seems to have no effect on the characteristics of the body model relative to the hand. Accordingly, the physiological mechanisms supporting the development of the implicit representation of hand dimensions in the healthy weight population may be preserved in obesity.

Obesity and Bone Loss at Menopause: The Role of Sclerostin.

Background. Peripheral fat tissue is known to positively influence bone health. However, evidence exists that the risk of non-vertebral fractures can be increased in postmenopausal women with obesity as compared to healthy controls. The role of sclerostin, the SOST gene protein product, and body composition in this condition is unknown. Methods. We studied 28 severely obese premenopausal (age, 44.7 ± 3.9 years; BMI, 46.0 ± 4.2 kg/m2) and 28 BMI-matched post-menopausal women (age, 55.5 ± 3.8 years; BMI, 46.1 ± 4.8 kg/m2) thorough analysis of bone density (BMD) and body composition by dual X-ray absorptiometry (DXA), bone turnover markers, sclerostin serum concentration, glucose metabolism, and a panel of hormones relating to bone health. Results. Postmenopausal women harbored increased levels of the bone turnover markers CTX and NTX, while sclerostin levels were non-significantly higher as compared to premenopausal women. There were no differences in somatotroph, thyroid and adrenal hormone across menopause. Values of lumbar spine BMD were comparable between groups. By contrast, menopause was associated with lower BMD values at the hip (p < 0.001), femoral neck (p < 0.0001), and total skeleton (p < 0.005). In multivariate regression analysis, sclerostin was the strongest predictor of lumbar spine BMD (p < 0.01), while menopausal status significantly predicted BMD at total hip (p < 0.01), femoral neck (p < 0.001) and total body (p < 0.05). Finally, lean body mass emerged as the strongest predictor of total body BMD (p < 0.01). Conclusions. Our findings suggest a protective effect of obesity on lumbar spine and total body BMD at menopause possibly through mechanisms relating to lean body mass. Given the mild difference in sclerostin levels between pre- and postmenopausal women, its potential actions in obesity require further investigation.