Estro-progestin and progestogen intake: What's the impact on hysteroscopic imaging?

Background: In current literature there is no report aimed to evaluate the effects of exogenous steroids on hysteroscopic imaging. Objectives: To evaluate the hysteroscopic features of endometrium in women undergoing female hormones administration. Materials and Methods: We reviewed video-records of hysteroscopies carried-out in women taking estro-progestins (EP), progestogen (P) and Hormonal Replacement Therapy (HRT). All women underwent biopsies resulting in atrophic, functional, or dysfunctional pathological reports. Main outcome measures: Description of hysteroscopic pictures related to each schedule of therapy. Results: The study included 117 women. We evaluated 82, 24 and 11 women treated by EP, P and HRT, respectively. In EP users, imaging indistinguishable from physiological pictures was found when high oestrogen dosage and low-potency progestogen as 17-OH progesterone derivatives were administered. By enhancing progestogen potency with 19-norprogesterone and 19-nortestosterone derivatives we observed a promotion of progestogen differentiation such as polypoid-papillary pseudo-decidualisation, spiral artery differentiation, inhibition of gland-proliferation and endometrial atrophy. In P users we distinguished two patterns, depending on continuous or sequential schedules. Continuous therapy resulted in atrophic or proliferative-secretory features whereas sequential ones led to endometrial overgrowth reflecting stromal pseudo-decidualisation. Women undergoing HRT showed atrophic features in combined continuous and polypoid overgrowth in sequential schedules. In women taking Tibolone we found pictures ranging from atrophic to hyperplastic appearances. Conclusions: Exogenous steroids lead to significant endometrial moulding. Depending on schedule, hysteroscopic-view appears predictable and often showing overgrowths mimicking proliferative pathologies. In this case biopsy is recommended but in common practice physicians should gain awareness with hysteroscopic pictures induced from hormone administration. What is new?: Systematic assessment of hysteroscopic pictures during estro-progestins intake.

Thyroid hormones and platelet activation in COVID-19 patients.

PURPOSE: To retrospectively describe the association between thyroid hormones (TH) and platelet activation, as represented by mean platelet volume (MPV), in a cohort of patients hospitalized for COVID-19 with no known thyroid disease, and to correlate these data with the severity of COVID-19 and the occurrence of death/ARDS (Acute Respiratory Distress Syndrome). METHODS: 103 patients with real-time polymerase chain reaction (RT-PCR) testing-confirmed COVID-19 and hospitalized were enrolled. Serum samples were collected from patients upon admission before starting any treatment. Chi-squared test was used to determine the association between euthyroid sick syndrome (ESS) and COVID-19 severity. Multivariate logistic regression was performed to evaluate the best independent predictors of COVID-19 deaths/ARDS. RESULTS: 39/103 (37.9%) of patients were found to have ESS, and this condition was an independent predictor for the severity of COVID-19 (p = 0.003). Lower TSH and lower FT3/FT4 ratio correlated with higher MPV (p = 0,001 and p = 0.010), with an opposite trend with respect to what has been documented in non-COVID patients. Increasing MPV and lower FT3 significantly increased the risk, in COVID-19 patients, of an adverse outcome of death/ARDS. CONCLUSION: Increased platelet activation, as represented by increased MPV, has already been reported to correlate with COVID-19 severity, possibly as a consequence of cytokine release. We demonstrated, in a cohort of 103 patients with COVID-19, that MPV is inversely correlated to TH levels, in particular in the case of ESS, where downregulation of TH axis may occur in case of systemic cytokine inflammation and more severe outcomes (death/ARDS). That ESS itself may directly cause platelet activation, as demonstrated by higher MPV in these patients, is an interesting hypothesis which deserves further investigation.

Visceral and subcutaneous adipose tissue as markers of local and systemic inflammation: a comparison between celiac and obese patients using MRI.

BACKGROUND: Celiac disease (CD) is a systemic inflammatory disease, which primarily affects the gastrointestinal tract. It has been recently demonstrated that adipose-tissue infiltration by proinflammatory immune cells causes a chronic low-grade inflammation in obese patients. Magnetic resonance imaging (MRI) has already proved to be useful in evaluation of inflammatory states. The aim of the present study was to determine whether alterations of visceral and subcutaneous adipose tissue, identified with MRI, could serve as markers of local and systemic inflammation in patients with CD. METHODS: A pilot study was conducted comparing alterations in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in CD patients vs obese patients and healthy controls. Fifty patients were enrolled and assigned to one of the following groups: Group A: 11 active CD patients; Group B: 11 CD patients in remission; Group C: 16 obese patients; Group D: 12 healthy controls. A 3-T MRI unit was used and T2-weighted TSE images of VAT and SAT were obtained in specific regions of interest. Serum cytokine concentrations (TNF-α, IL-6, adiponectin, leptin, IL-2, IFN-γ) were determined. RESULTS: There was a significant difference in VAT T2 relaxation time between Group A and B (p < 0.001), A and D (p < 0.01), B and C (p < 0.001). There was a statistically significant difference in SAT T2 relaxation time between Group A and B (p < 0.001), A and C (p < 0.05), A and D (p < 0.001), B and C (p < 0.01). In addition, VAT/SAT T2 relaxation time ratio showed a statistically significant difference between Group A and C (p < 0.05) and between Group B and C (p < 0.01). Only TNF-α and IL-6 significantly correlated with both VAT and VAT/SAT ratio in active CD. CONCLUSIONS: MRI showed similar increased visceral inflammatory signals in patients with active CD and obese patients. However, subcutaneous inflammatory signals were higher in active CD than in all the other groups. These data show that there is a systemic inflammatory state in active CD, whereas chronic inflammation appears confined to VAT in obesity. These data were only partially confirmed by serological cytokine profiles, which showed less specificity than MRI.

Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE).

BACKGROUND: Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications. PURPOSE: We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life.

Impact of CFTR-modulating drugs on GH-IGF-1 axis impairment in adult patients with cystic fibrosis.

INTRODUCTION: A new class of drugs in the treatment of cystic fibrosis (CF) includes two agents: lumacaftor, which corrects CFTR channel protein, and ivacaftor, which increases CFTR channel activity. In our previous study we recruited 50 stable adults with CF and 16 of them showed growth hormone deficit (GHD): 7 patients severe and 9 patients partial GHD. MATERIAL AND METHODS: We decided to re-evaluate ten patients with the GHRH + arginine test of whom only five were treated with lumacaftor/ivacaftor. RESULTS: All CF patients in therapy with lumacaftor/ivacaftor showed a marked improvement in GHD. Two patients moved from a severe GHD to a normal response to the GH/IGF-1 axis test, and three patients who had partial GHD moved to normal response. CONCLUSION: The pituitary gland may be damaged by CF disease and could benefit of the action of correcting drugs.

Analysis of characteristics and outcomes by growth hormone treatment duration in adult patients in the Italian cohort of the Hypopituitary Control and Complications Study (HypoCCS).

PURPOSE: To examine differences in effects according to growth hormone (GH) treatment duration in adult GH-deficient patients. METHODS: In the Italian cohort of the observational Hypopituitary Control and Complications Study, GH-treated adults with GH deficiency (GHD) were grouped by duration of treatment; ≤ 2 years (n = 451), > 2 to ≤ 6 years (n = 387) and > 6 years (n = 395). Between-group differences in demographics, medical history, physical characteristics, insulin-like growth factor-I standard deviation score (IGF-I SDS) and lipid profile at baseline, last study visit and changes from baseline to last study visit were assessed overall, for adult- and childhood-onset GHD and by gender using ANOVA for continuous variables and Chi-squared test for categorical variables. RESULTS: At baseline, treatment duration groups did not differ significantly for age, gender, body mass index, GHD onset, IGF-I SDS, lipid profile, and quality of life. Mean initial GH dose did not differ significantly according to treatment duration group in any subgroup, except female patients, with highest mean dose seen in the longest duration group. In the longest duration group for patients overall, adult-onset patients and male patients, there were significant decreases in GH dose from baseline to last visit, and in total and low-density lipoprotein (LDL)-cholesterol concentrations. IGF-I SDS increased, to a greater extent, in the longest duration group for patients overall and female patients. CONCLUSIONS: The results show that long-term GH treatment is associated with decreasing GH dose, increased IGF-I, decreased LDL-cholesterol and the presence of surrogate markers that help to give confidence in a diagnosis of GHD.

Impaired taste sensation in type 2 diabetic patients without chronic complications: a case-control study.

PURPOSE: Few and contradictory data suggest changes in taste perception in type 2 diabetes (T2DM), potentially altering food choices. We, therefore, analyzed taste recognition thresholds in T2DM patients with good metabolic control and free of conditions potentially impacting on taste, compared with age-, body mass index-, and sex-matched normoglycemic controls. METHODS: An ascending-concentration method was used, employing sucrose (sweet), sodium chloride (salty), citric acid (sour), and quinine hydrochloride (bitter), diluted in increasing concentration solutions. The recognition threshold was the lowest concentration of correct taste identification. RESULTS: The recognition thresholds for the four tastes were higher in T2DM patients. In a multiple regression model, T2DM [ß = 0.95; 95% CI 0.32-1.58; p = 0.004 (salty); ß = 0.61; 0.19-1.03; p = 0.006 (sweet); ß = 0.78; 0.15-1.40; p = 0.016 (sour); ß = 0.74; 0.22-1.25; p = 0.006 (bitter)] and waist circumference [ß = 0.05; 0.01-0.08; p = 0.012 (salty); ß = 0.03; 0.01-0.05; p = 0.020 (sweet); ß = 0.04; 0.01-0.08; p = 0.020 (sour); ß = 0.04; 0.01-0.07; p = 0.007 (bitter)] were associated with the recognition thresholds. Age was associated with salty (ß = 0.06; 0.01-0.12; p = 0.027) and BMI with sweet thresholds (ß = 0.06; 0.01-0.11; p = 0.019). CONCLUSIONS: Taste recognition thresholds were higher in uncomplicated T2DM, and central obesity was significantly associated with this impairment. Hypogeusia may be an early sign of diabetic neuropathy and be implicated in the poor compliance of these patients to dietary recommendations.

Deregulation of the growth hormone/insulin-like growth factor-1 axis in adults with cystic fibrosis.

PURPOSE: Patients with cystic fibrosis (CF) present with signs and symptoms that overlap with those of adult growth hormone deficiency (GHD) syndrome: loss of muscle mass, bone fragility and lower stress tolerance. In literature, the prevalence of GHD in pediatric CF patients is higher than general population, but these studies have been performed on children with growth delay. To our knowledge, there are no studies on adult patients. The aim of this paper is to evaluate GH-IGF1 axis in an adult CF population. METHODS: Fifty clinically stable adult patients, 30 males; age 36 ± 2 years; BMI 21.39 ± 0.22 kg/m2 and FEV1 67 ± 4% were studied. Data regarding glycometabolic status and results of pituitary, thyroid, parathyroid, gonadal and adrenal function tests were recorded. All patients underwent a GH releasing hormone (GHRH) + Arginine stimulation test to confirm a GHD. RESULTS: GHRH + Arginine test revealed the presence of GHD in 16 patients (32%); specifically 7 patients had a severe deficiency and 9 a partial deficiency. CONCLUSIONS: Adult patients with CF may show GHD. These patients should be followed over time to assess if the GHD could impact the clinical progression of CF.

Sarcopenic Obesity and Metabolic Syndrome in Adult Caucasian Subjects.

OBJECTIVES: Recently metabolic aspects linked to sarcopenic obesity (SO) were investigated. Extant studies involved especially older people from Asian or White-mixed American cohorts. THE AIMS OF OUR STUDY WERE: to explore the prevalence of sarcopenia in Caucasian adult obese subjects using two different indices of sarcopenia, and to investigate the relationship among SO, metabolic syndrome (MS), inflammation, and serum albumin concentrations. DESIGN: Cross- sectional study. SUBJECTS/METHODS: The study was performed from 2011 to 2014 in a hospitalized care setting. Inclusion criteria were: age>18 and <65 years, BMI≥30 Kg/m2. Fat mass (FM) and fat-free mass (FFM) were assessed by DXA. Appendicular skeletal muscle mass (ASMM) was calculated. Sarcopenia was defined as ASMM/height2 or ASMM/weight <2SD than the sex-specific mean of a young population. The cutoffs were ASMM/h2<6.54 Kg/m2 for men and 4.82 Kg/m2 for women, and ASMM/weight<0.2827 for men and 0.2347 for women. ISI-Matsuda was calculated. MS was diagnosed (NCEP-ATPIII). RESULTS: 727 subjects (age: 45.72±13.56 years, BMI: 37.74±5.82 kg/m2) were enrolled. The prevalence of SO was 1.0% or 34.8% in men and 0.6% or 50.1% in women, using ASMM/height2 ratio or ASMM/weight. Subjects with SO based on ASMM/height2 were scarce, only data relying on ASMM/weight were considered. Subjects with SO had higher BMI, waist circumference, FM, and lower FFM and ASMM than nonsarcopenic obese individuals (all p<0.05). ISI-Matsuda was lower and hs-CRP levels were higher in subjects with SO (all p<0.05). MS was more prevalent in subjects with SO than nonsarcopenic obese subjects (47.6% vs 34.3%, p<0.001). ASMM/weight was decreased in subjects with MS (0.2522±0.0410 vs 0.2423±0.0352, p=0.001). CONCLUSION: SO is associated with MS and low- grade inflammation in adult Caucasian subjects. Metabolic profile evaluation should be recommended in subjects with SO.

Circulating SIRT1 inversely correlates with epicardial fat thickness in patients with obesity.

BACKGROUND AND AIM: Obesity is increasing worldwide and is related to undesirable cardiovascular outcomes. Epicardial fat (EF), the heart visceral fat depot, increases with obesity and correlates with cardiovascular risk. SIRT1, an enzyme regulating metabolic circuits linked with obesity, has a cardioprotective effect and is a predictor of cardiovascular events. We aimed to assess the relationship of EF thickness (EFT) with circulating SIRT1 in patients with obesity. METHODS AND RESULTS: Sixty-two patients affected by obesity and 23 lean controls were studied. Plasma SIRT1 concentration was determined by enzyme-linked immunosorbent assay (ELISA). EFT was measured by echocardiography. Body mass index (BMI), waist circumference, heart rate (HR), blood pressure, and laboratory findings (fasting glucose, insulin, HbA1c, cholesterol, and triglycerides) were assessed. SIRT1 was significantly lower (P = 0.002) and EFT was higher (P < 0.0001) in patients with obesity compared with lean controls. SIRT1 showed a negative correlation with EFT and HR in the obesity group (ρ = -0.350, P = 0.005; ρ = -0.303, P = 0.008, respectively). After adjustment for obesity-correlated variables, multiple linear regression analysis showed that EFT remained the best correlate of SIRT1 (ß = -0.352, P = 0.016). CONCLUSIONS: Circulating SIRT1 correlates with the visceral fat content of the heart. Serum SIRT1 levels might provide additional information for risk assessment of coronary artery disease in patients with obesity.

Lean mass in obese adult subjects correlates with higher levels of vitamin D, insulin sensitivity and lower inflammation.

AIM: Several chronic metabolic alterations are present in obese subjects. While it is well known about the detrimental effect of abdominal adipose tissue on chronic metabolic clinical condition, less is known on the role of lean mass in obese subjects. Thus, the aim of our study was to evaluate the potential correlation of muscle mass, metabolic condition and inflammation status in obese individuals. METHODS: The study included 426 obese subjects (86 men and 340 female; mean age 44.8 ± 14 years; BMI: 34.9 ± 6.1 kg/m(2)). Exclusion criteria were chronic medical conditions or use of medications affecting bone metabolism, alterations of hormonal and nutritional status, vitamin D supplementation, recent weight loss and prior bariatric surgery. Patients underwent measurements of bone mineral density (lumbar and hip) and body composition (lean mass, total and trunk fat mass) by dual X-ray absorptiometry and were evaluated for hormonal and metabolic profile and inflammatory markers. RESULTS: Higher lean body mass (LM%) was inversely correlated with homeostasis model assessment of insulin resistance (p < 0.0091; r(2) 0.03938) and associated with lower fibrinogen levels (p < 0.0001; r(2) 0.1263). Interestingly, in obese subjects, LM% was associated with higher levels of vitamin D (p < 0.0001, r(2) 0.1140), osteocalcin (p < 0.0001, r(2) 0.2401) and insulin-like growth factor-1 (IGF-1) (p < 0.0002, r(2) 0.1367). CONCLUSION: Our results show for the first time that in obese patients, higher amounts of lean mass are directly linked to a lower inflammatory profile and to better insulin sensitivity, but also to the presence of higher level of vitamin D and IGF-1. Moreover, these data suggest that higher levels of lean mass in obese people correlate with a better metabolic profile and, thus, strongly suggest the need to develop programs to facilitate an increase in physical activity in obese people.

Oligogalacturonides improve tissue organization of in vitro reconstructed skin.

The aim of this study was to analyse the effects of oligogalacturonides obtained from apple pectin enzymatic hydrolysis (mainly composed of galacturonic acid and oligogalacturonides; OGA) on normal human keratinocytes behaviour using different in vitro models. We demonstrate that 0.01% OGA promotes epidermal growth, organization and stratification in an in vitro reconstructed skin. The presence and the in vivo-like location of epidermal differentiation markers (i.e. keratin 10, involucrin, desmoglein 1 and 3, and cathepsin D) confirms the histological analysis, and underlines the cohesion of the treated epidermis. On the opposite, 0.05% OGA delays epidermal growth and disturbs differentiation, showing that the positive effects of OGA are dependent on its concentration. In parallel, using collagen IV and laminin 332 substrates, two relevant components of dermal-epidermal basement membrane, we demonstrate that the presence of 0.01% OGA clearly stimulates keratinocytes spreading out, paralleled by a well-organized microfilament network. Keratinocytes develop more focal adhesions with the substrates, implicating α6ß4 on laminin 332. Cellular cohesion is also promoted by 0.01% OGA through the over-expression of integrins α2ß1 on collagen IV, and α3ß1 on laminin 332 at cell-cell junctions. Thus, by modulating integrins expression and organization, OGA 0.01% should improve cell-cell interactions and therefore dermal-epidermal cohesion. In conclusion, 0.01% OGA stimulates epidermal spreading and promotes keratinocytes attachment to basement membrane components by reorganizing cytoskeleton and modulating integrins recruitment. Furthermore, 0.01% OGA promotes epidermal differentiation and regulates epidermis homeostasis. Considering that OGA has a beneficial effect on parameters playing a key role in ageing, OGA can be presented as a new anti-ageing active ingredient.

[Obesity and Eating Disorders. Indications for the different levels of care. An Italian Expert Consensus Document]. / Documento di Consensus. Obesità e Disturbi dell'Alimentazione Indicazioni per i diversi livelli di trattamento.

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.

Is obesity protective for osteoporosis? Evaluation of bone mineral density in individuals with high body mass index.

BACKGROUND: Obese individuals often present comorbidities while they appear protected against the development of osteoporosis. However, few and contradictory data are now available on skeletal modifications in obese patients. The aim of this study was to characterise bone mineral density (BMD) in overweight (BMI > 25 < 29.9) and obese (BMI > 30) patients. METHODS: We selected 398 patients (291 women, 107 men, age 44.1 + 14.2 years, BMI 35.8 + 5.9 kg/m(2)) who underwent clinical examination, blood tests and examination of body composition. Subjects with chronic conditions or taking medications interfering with bone metabolism, hormonal and nutritional status and recent weight loss were excluded. RESULTS: Interestingly, 37% (n = 146) of this population showed a significantly lower than expected lumbar BMD: 33% (n = 98) of women showed a T-score -1.84 +/- 0.71, and 45% (n = 48) of men showed a T-score -1.88 +/- 0.64. When the population was divided into subgroups based on different BMI, it was noted that overweight (BMI > 25 < 29.9) was neutral or protective for BMD, whereas obesity (BMI > 30) was associated with a low bone mass, compatible with a diagnosis of osteoporosis. No differences were observed in hormones and lipid profiles among subgroups. CONCLUSIONS: Our results indicate that a subpopulation of obese patients has a significant low lumbar BMD than expected for age. Thus, a careful characterisation of skeletal metabolism might be useful in all obese individuals to avoid fragility fractures later in life.

Metabolic or bariatric surgery? Long-term effects of malabsorptive vs restrictive bariatric techniques on body composition and cardiometabolic risk factors.

BACKGROUND: Obesity is an increasing health problem and surgery seems to be the only treatment effective in achieving weight loss without relapse. Among bariatric techniques, many differences exist in terms of weight loss and resolution of comorbidities. Up to now, there are no prospective studies comparing long-term effects of malabsorptive vs restrictive techniques. OBJECTIVE: In this study, cardiometabolic risk factors and body composition changes after malabsorptive biliointestinal bypass (BIBP) and restrictive laparoscopic adjustable gastric banding (LAGB) were compared during a 4-year follow-up. DESIGN: Prospective, case-control and cohort study. PATIENTS: In all, 80 obese subjects, matched for weight and age. Altogether, 40 patients underwent BIBP and 40 underwent LAGB. MEASUREMENTS: Weight, body composition, fasting and post-loading plasma glucose and insulin, homeostatic model assessment index (HOMA-I), lipid profile, blood pressure (BP), erythrocyte sedimentation rate and fibrinogen were monitored at baseline, 12 and 48 months. RESULTS: At 12 months after surgery, a significant reduction in body mass index, total fat mass (FM), trunk FM (trFM), trFM/legs FM (lFM) ratio (trFM/lFM), triglycerides, BP and inflammation markers was observed in both groups. BIBP patients showed a significant reduction in total cholesterol (Tot-C), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), whereas the LAGB group showed a significant increase of HDL-C. A further improvement of all the parameters evaluated was seen in the BIBP group at 48 months after surgery. CONCLUSIONS: Both bariatric procedures exerted positive effects on cardiometabolic risk factors and on weight loss in the population studied, but on the long-term period, HOMA-I, Tot-C/HDL-C ratio and body composition improvements were more evident after BIBP. We conclude that malabsorptive BIBP seems to be more effective than LAGB in treating visceral obesity and its metabolic complications.

Efficacy of genistein aglycone on some cardiovascular risk factors and homocysteine levels: A follow-up study.

BACKGROUND AND AIM: Recent evidence suggests that genistein aglycone may act beneficially on surrogate cardiovascular risk markers in postmenopausal women. We assessed the effects of genistein aglycone on some cardiovascular risk factors and homocysteine levels after 3-years of continued therapy in a cohort of osteopenic, postmenopausal women. METHODS AND RESULTS: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 postmenopausal women with low bone mass for 24 months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54mg of genistein aglycone (n=71) or placebo (n=67), daily. Both arms received calcium and vitamin D(3) in therapeutic doses. Moreover, 4 weeks before randomization procedures and during our follow-up study, all patients received dietary instructions in an isocaloric fat-restricted diet. Blood lipid profiles, fasting glucose and insulin, insulin resistance (HOMA-IR), fibrinogen, osteoprotegerin (OPG) and homocysteine at baseline and after 24 and 36 months of treatment were measured. Compared to placebo, genistein significantly decreased fasting glucose and insulin, HOMA-IR, fibrinogen and homocysteine after 24 and 36 months of treatment. By contrast, isoflavone administration did not affect high-density lipoprotein cholesterol and triglycerides though serum OPG was higher in the genistein recipients. There were no differences in adverse events or discomfort between groups. Results on routine biochemical, liver function, and hematologic testing did not change over time in placebo or genistein group. CONCLUSIONS: After 3-years of treatment, genistein aglycone plus calcium, vitamin D(3) and a healthy diet showed positive effects on some cardiovascular risk factors and homocysteine levels in a cohort of postmenopausal women with low bone mass.

Reduction of risk factors for cardiovascular diseases in morbid-obese patients following biliary-intestinal bypass: 3 years' follow-up.

BACKGROUND: Obese patients are often affected by hypertension, dyslipidaemia, impaired glucose metabolism, and suffer from cardiovascular disease (CVD), related to the characteristic metabolic alterations. AIM OF THE STUDY: To evaluate reduction of risk factors for CVDs in morbid-obese patients (body mass index (BMI)>40 kg/m2) after weight loss upon bariatric surgery intervention of biliary-intestinal bypass. SUBJECTS: 45 (17 men, 28 women) morbid-obese patients (age: 19-49 y, BMI>40 kg/m2). All patients were selected on the basis of medical history, physical and biochemical evaluation and of psychiatric tests, which were performed on all individuals admitted to our Day Hospital to verify the safety of surgical intervention. MEASUREMENTS: Body weight, body composition (by dual X-ray absorptiometry, DXA), blood pressure, lipid profile, fibrinogen and glucose metabolism were monitored at baseline and 1, 3, 6, 9, 12, 24 and 36 months after surgery. RESULTS: A significant and persistent weight loss was present in all patients at the end of the 3 y follow-up period (P<0.001), with a progressive reduction of total and trunk fat mass as evaluated by means of DXA. Additionally, a parallel significant reduction in systolic (P<0.001) and diastolic (P<0.001) blood pressure was observed. Total and LDL cholesterol were significantly reduced (P<0.001), while HDL showed no modifications; triglycerides declined progressively during the 3 y follow-up (P<0.001). Fibrinogen decreased from 364.5+/-82.4 to 266.4+/-45.7 mg/dl at the end of the period (P<0.001). Fasting glucose levels and glucose levels 120 min after an oral glucose tolerance test were reduced from 95.1+/-20.3 to 78.6+/-9.1 mg/dl (P<0.001) and from 116.9+/-34.7 to 77.6+/-15.5 mg/dl (P<0.001), respectively, at baseline and at the end of the study. Moreover, fasting insulin decreased from 30.0+/-20.4 to 8.6+/-2.9 microUI/ml (P<0.001) after 3 y, while insulin levels after (120 min) oral glucose load decreased from 105.5+/-61.5 to 12.0+/-6.0 microUI/ml (P<0.001). CONCLUSION: Our results show that biliary-intestinal bypass may represent a valid and alternative therapeutic approach in patients with morbid obesity since it induces a significant and stable reduction of body weight and obesity-related risk factors for CVD.