Bariatric surgery modulates plasma levels of antibodies against angiotensin II type 1 and endothelin 1 type A receptor in severe obesity.

PURPOSE: The contribution of endothelial-targeted autoantibodies against the angiotensin II type 1 receptor (anti-AT1R) and the anti-endothelin 1 type A receptor (anti-ETAR1) has been proposed in the development of cardiovascular diseases. However, no data have been reported yet in obesity. In this observational study we evaluated the relationship between anthropometric and metabolic parameters and anti-AT1R and anti-ETAR1 concentrations in a cohort of patients with severe obesity and associated comorbidities undergoing bariatric surgery. METHODS: Clinical evaluation and metabolic assessment were performed in 36 subjects referring to our Center for the Study and Integrated Treatment of Obesity at the University Hospital of Padova. Circulating inflammatory adipocytokines and the endothelial dysfunction marker asymmetric dimethylarginine (ADMA) were evaluated; plasma levels of anti-AT1R and anti-ETAR1 were also determined. 10 normal-weight subjects were considered as a control group. 29 patients out of 36 were re-evaluated after surgery. RESULTS: With respect to normal-weight controls patients showed significantly higher plasma levels of anti-AT1R (28 ± 20.4 vs 13.5 ± 2.8 U/mL, p < 0.005) and ADMA (0.8 ± 0.1 vs 0.54 ± 0.08 uM/L, p < 0.0001) but not anti-ETAR1 (14.2 ± 1.3 vs 13.3 ± 2 U/mL, p = 0.1). Anti-AT1R concentration showed an increasing trend with the worsening of glycemic status, while the presence of arterial hypertension among the patients did not affect autoantibodies levels. One year after surgery, a significant improvement in body weight and metabolic and inflammatory parameters was observed, along with a significant reduction of anti-AT1R (28.1 ± 20.4 U/mL vs 22.6 ± 16 U/mL, p < 0.05) and anti-ETAR1 (14.2 ± 1.3 U/L vs 13 ± 1.6 U/L, p < 0.01). CONCLUSIONS: Subjects with obesity present higher plasma levels of anti-AT1R which are more related to glycemic profile than blood pressure levels, and are reduced by bariatric surgery. Considering the detrimental effects of these autoantibodies on vascular health, they should be assessed as potential biomarkers in obesity and metabolic diseases.

Italian guidelines for the management of adult individuals with overweight and obesity and metabolic comorbidities that are resistant to behavioral treatment.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification. METHODS: Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote. RESULTS: The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m2 and < 40 kg/m2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative. CONCLUSION: The present GL is directed to all physicians addressing people with obesity-working in hospitals, territorial services or private practice-and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

Treatment with dapagliflozin increases FGF-21 gene expression and reduces triglycerides content in myocardial tissue of genetically obese mice.

BACKGROUND: The association between obesity and some cardiovascular complications such as heart failure (HF) is well established, and drugs affecting adiposity are supposed to be promising treatments for these conditions. The sodium-glucose cotransporter-2 inhibitors (SGLT2i) are antidiabetic drugs showing benefits in patients with HF, despite the underlying mechanisms have not been completely understood yet. SGLT2i are supposed to promote systemic effects, such as triglycerides mobilization, through the enhancement of fibroblast growth factor-21 (FGF-21) activity. So, in this study, we evaluated the effects of dapagliflozin treatment on FGF-21 and related receptors (FGF-Rs) gene expression and on lipid content in myocardial tissue in an animal model of genetically induced obesity to unravel possible metabolic mechanisms accounting for the cardioprotection of SGLT2i. METHODS: Six-week-old C57BL/6J wild-type mice and B6.V-LEP (ob/ob) mice were randomly assigned to the control or treatment group (14 animals/group). Treatment was based on the administration of dapagliflozin 0.15 mg/kg/day for 4 weeks. The gene expression of FGF-21 and related receptors (FGF-R1, FGF-R3, FGF-R4, and ß-klotho co-receptor) was assessed at baseline and after treatment by real-time PCR. Similarly, cardiac triglycerides concentration was measured in the control group and treated animals. RESULTS: At baseline, FGF-21 mRNA expression in the heart did not differ between lean and obese ob/ob mice. Dapagliflozin administration significantly increased heart FGF-21 gene expression, but only in ob/ob mice (p < 0.005). Consistently, when measuring the amount of triglycerides in the cardiac tissue, SGLT2i treatment reduced the lipid content in obese ob/ob mice, while no significant effects were observed in treated lean animals (p < 0.001). The overall expression of the FGF-21 receptors was only minimally affected by dapagliflozin treatment both in obese ob/ob mice and in lean controls. CONCLUSIONS: Dapagliflozin administration increases FGF-21gene expression and reduces triglyceride content in myocardial tissue of ob/ob mice, while no significant effect was observed in lean controls. These results might help understand the cardiometabolic effects of SGLT2i inducing increased FGF-21 synthesis while reducing lipid content in cardiomyocytes as a possible expression of the switch to different energy substrates. This mechanism could represent a potential target of SGLT2i in obesity-related heart diseases.

Putative circulating adipose tissue-derived stem cells, obesity, and metabolic syndrome features.

PURPOSE: In mice, adipose tissue-derived stem cells (ASCs) reach the systemic circulation and establish ectopic adipose depots fostering insulin resistance, but whether this occurs in humans is unknown. We examined circulating ASCs in individuals with various combination of metabolic syndrome traits. METHODS: We enrolled patients attending a routine metabolic evaluation or scheduled for bariatric surgery. We quantified ASCs as CD34+CD45-CD31-(CD36+) cells in the stromal vascular fraction of subcutaneous and visceral adipose tissue samples and examined the presence and frequency of putative ASCs in peripheral blood. RESULTS: We included 111 patients (mean age 59 years, 55% males), 40 of whom were scheduled for bariatric surgery. The population of CD34+CD45-CD31- ASCs was significantly more frequent in visceral than subcutaneous adipose depots (10.4 vs 4.1% of the stromal vascular fraction; p < 0.001), but not correlated with BMI or metabolic syndrome traits. The same phenotype of ASCs was detectable in peripheral blood of 58.6% of patients. Those with detectable circulating ASCs had significantly higher BMI (37.8 vs 33.3 kg/m2; p = 0.003) and waist (111.2 vs 105.4 cm; p = 0.001), but no difference in other metabolic syndrome traits (p = 0.84). After bariatric surgery, patients with detectable circulating ASCs had greater BMI reductions at 6 months (- 10.4 vs - 7.8 kg/m2; p = 0.014). CONCLUSION: Presence of putative circulating ASCs, antigenically similar to those observed in the adipose tissue, is associated with greater adiposity and larger BMI reduction after surgery, but not with clinical signs of metabolic impairment. The role of circulating ASCs in adipose tissue biology and systemic metabolism deserves further investigation.

Management of Hypothyroidism in Internal Medicine: Patient Profile and Effects of an Educational Programme in the Cluster-Randomized FADOI TIAMO Study.

Background and aims: There is still limited knowledge regarding the clinical profile and appropriateness of treatment in patients with hypothyroidism hospitalized in Internal Medicine (IM) Departments in Italy. The aim of this study is to evaluate: 1) the characteristics of patients and possible deviations from national and international clinical practice recommendations (CPRs) in evidence-based guidelines (EBGs); 2) the improvement of patient management by means of a standardized educational programme (EP). Methods: A nationwide multicentre study, comprising two replications of a retrospective survey (phases 1 and 3) with an intervening EP (phase 2) in half of the centres and no EP in the other half, was conducted. The EP was based on outreach visits. Centres were assigned to the two arms of the study, labelled the training group (TG) and control group (CG) respectively, by cluster randomization. Four EBGs and 39 CPRs provided the basis on which 22 treatment management indicators were identified (7 referring to the time of hospital admission, 15 to post-admission). Results: The 21 participating centres recruited 587 hospitalized patients with hypothyroidism, 421 of which were females (71.7%, mean age 74.1 + 14.4 yrs): 318 in phase 1 and 269 in phase 3. The cause of hypothyroidism was unknown in 282 patients (48%). Evaluation at the time of admission identified satisfactory adherence to CPRs (>50%) for 63.6% of the indicators. In the phase 3, TG centres showed significant improvement vs CG in 4 of the 15 post-admission indicators, while 1 out of 15 was significantly worse. Conclusions: The EP based on outreach visits significantly improved some indicators in the management of patients with hypothyroidism, with specific reference to appropriateness of TSH dosage and levothyroxine (LT4) treatment modality. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05314790.

Questionnaire and tools: clinical powerful instrument in acromegaly diagnosis and management.

PURPOSE: Acromegaly is a rare chronic disease characterized by systemic comorbidity and reduced quality of life. Although achieving biochemical control has always been the primary goal of acromegaly therapy, recent evidence has shown that the traditional assessment does not adequately capture the complexity of symptoms and patients' perception. These findings result in the need to improve a fast decision-making process of the clinician, who should not only take into account biochemical-instrumental criteria, but also patients' symptoms. With the aim of supporting the clinician in the diagnostic and therapeutic decision-making process several disease-specific tools have been developed. The aim of this review is to provide a description of the acromegaly-specific tools, presenting their main features, their application in daily practice, and their efficacy and utility. METHODS: A systematic search of Medline/PubMed, ISI-Web of Knowledge, and Google Scholar databases was done. RESULTS: Specific instruments and questionnaires have recently been developed to assist clinicians in the assessment of acromegaly. These are either Patient-Reported Outcome tools, such as Acromegaly Quality of Life Questionnaire (AcroQoL) and Pain Assessment Acromegaly Symptom Questionnaire (PASQ), or Clinician-Reported Outcome tools, such as ACROSCORE, SAGIT® and Acromegaly Disease Activity Tool (ACRODAT®). Such tools are extremely flexible and, therefore, have been widely adopted by endocrinologists and other professionals, so much so that they have also been included as recommendations in the 2018 international guidelines. CONCLUSION: Questionnaires and tools are useful in the management of acromegaly patients. They help clinicians evaluate patients' symptoms and could assist in the evaluation of disease activity.

Safety and effectiveness of Omnitrope® in patients with growth hormone deficiency: snapshot analysis of PATRO Adults study in the Italian population.

PURPOSE: PATRO adults is an ongoing, multicenter, observational, post-marketing surveillance study aimed at investigating the long-term safety (primary endpoint) and effectiveness (secondary endpoint) of the recombinant human growth hormone (rhGH) Omnitrope® during routine clinical practice. This report describes data from Italian participants in PATRO Adults with growth hormone deficiency (GHD), up to August 2017. METHODS: Participants were adults (aged > 18 years) with GHD requiring rhGH therapy and were prescribed Omnitrope®, including those who had previously received another rhGH product. Adverse events (AEs) were evaluated in all study participants. Data were collected on insulin-like growth factor (IGF)-I levels and cardiovascular risk factors, including blood pressure, lipids, and anthropometric parameters. RESULTS: From September 2007 to August 2017, 88 patients (mean age 48.9 years, 58.0% male) were enrolled at 8 sites in Italy. The mean treatment duration with Omnitrope® was 51.5 ± 37 months. AEs occurred in 54 patients; the most common were asthenia (20.5%), headache (14.8%), and arthralgia (13.6%). Serious AEs occurred in 22 patients (25%), including pneumonia (n = 2) and renal failure (n = 2). Neoplasms (2 benign and 1 malignant) developed in three patients, but none were considered to be drug-related. There were no significant changes in fasting glucose or glycosylated hemoglobin (HbA1c) during the study period. Long-term Omnitrope® therapy showed slight positive effects on lipid profile, while no significant changes were observed in body weight and BMI during the study. CONCLUSION: This snapshot analysis of Italian participants in PATRO Adults confirmed the long-term safety and effectiveness of Omnitrope® in adults with GHD.

Electrophysiological features in acromegaly: re-thinking the arrhythmic risk?

BACKGROUND: Acromegaly is disease associated with a specific cardiomyopathy. Hitherto, it has been widely understood that acromegaly carries an increased risk of arrhythmia. PURPOSE: In this review we show that evidences are limited to a small number of case-control studies that reported increased rates of premature ventricular beats (PVB) but no more significant arrhythmia. In contrast, there are several studies that have reported impaired preclinical markers of arrhythmia, including reduced heart rate variability, increased late potentials, QT interval dispersion, impaired heart rate recovery after physical exercise and left ventricular dysynchrony. Whilst these markers are associated with an adverse cardiovascular prognosis in the general population, they do not have a high independent positive predictive accuracy for arrhythmia. In acromegaly, case reports have described sudden cardiac death, ventricular tachyarrhythmia and advanced atrio-ventricular block that required implantation of a cardio-defibrillator or permanent pacemaker. Treatment with somatostatin analogues can reduce cardiac dysrhythmia in some cases by reducing heart rate, PVBs and QT interval. Pegvisomant reduces mean heart rate. Pasireotide is associated with QT prolongation. In the absence of good quality data on risk of arrhythmia in acromegaly, the majority of position statements and guidelines suggest routine 12-lead electrocardiography (ECG) and transthoracic echocardiography (TTE) in every patient at diagnosis and then follow up dependent on initial findings.

The prevalence of silent acromegaly in prolactinomas is very low.

PURPOSE: The aim of this study was to evaluate the somatotroph axis in a large series of patients with prolactinoma to verify the prevalence of silent acromegaly in this population. METHODS: A hundred and forty-four patients were enrolled in a multicenter study: 90 were already on cabergoline (CAB) and enrolled in a cross-sectional arm (group A) with random PRL, GH and IGF-I determination on treatment (≥ 3 months), whereas 54 untreated patients were enrolled at diagnosis in a prospective arm (group B) with PRL, GH and IGF-I measurement before and after 6 and 12 months of treatment. In the presence of high IGF-I, CAB was withdrawn for 3 months and GH, IGF-I, PRL and GH during an oral Glucose Tolerance Test (OGTT) were obtained. RESULTS: High IGF-I levels (ULN 1.01-1.56) were observed in 9 patients (6.25%, 5F). After CAB withdrawal, IGF-I levels normalized in 5/9 patients, GH was < 0.4 ng/ml after OGTT in 7/9 cases or at random GH determination in one case. After CAB re-introduction, IGF-I levels re-increased in a single case. Overall, a single young female patient harboring a macroadenoma in group A was diagnosed with silent acromegaly and underwent successful transsphenoidal removal of a GH/PRL-secreting adenoma. CONCLUSION: The prevalence of silent acromegaly in prolactinomas (0.7%) is lower than previously reported and OGTT is helpful to recognize silent acromegaly. We suggest that the somatotroph axis should be evaluated at diagnosis in all cases and not systematically during follow-up.

Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532).

BACKGROUND: Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on binding of the viral spike (S) proteins to angiotensin-converting enzyme 2 and on S protein priming by TMPRSS2. Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is up-regulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections. MATERIALS AND METHODS: We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV-2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the coronavirus disease 2019 (COVID-19) pandemic. The parameters used for each COVID-19-positive patient were sex, hospitalization, admission to intensive care unit, death, tumor diagnosis, prostate cancer diagnosis, and ADT. RESULTS: There were evaluable 9280 SARS-CoV-2-positive patients in Veneto on 1 April 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2-positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT (OR 4.05; 95% CI 1.55-10.59). A greater difference was found comparing prostate cancer patients receiving ADT with patients with any other type of cancer (OR 4.86; 95% CI 1.88-12.56). CONCLUSION: Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections compared with non-cancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections.

Ovarian 25OH-vitamin D production in young women affected by polycystic ovary syndrome.

INTRODUCTION: Vitamin D is involved in the regulatory mechanisms of ovarian function and is frequently low in PCOS patients. Since obesity and hyperinsulinemic state negatively influenced vitamin D levels, therefore, we evaluated the production of vitamin D at the ovarian level only in lean and normoinsulinemic PCOS subjects. Basal, GnRH analogue-induced ovarian production of 25OH-vitamin D (VitD) and a direct sampling at ovarian vein level were investigated. METHODS: Basal and GnRH analogue-induced hormone levels were evaluated at peripheral level in 45 subjects, aged 18-39 years, and in 22 healthy women with age- and BMI-matched as controls. In 12 PCOS patients, undergoing laparoscopy, a venous sampling at both peripheral and ovarian level was further done. All subjects presented low VitD levels, appropriate to the season and with no difference between PCOS and control subjects. RESULTS: GnRH analogue significantly stimulated plasma LH, FSH, 17-OHP and estradiol secretion (p from < 0.05 to < 0.001 vs basal levels), whereas no effect was observed on both serum AMH and VitD concentrations in all groups. A significant difference (p < 0.006), between peripheral and ovarian veins, was observed in both AMH and estradiol levels in PCOS subjects, while no gradient of VitD was detected. CONCLUSIONS: All patients presented with low VitD levels. The absence of any VitD variation, both at basal and after GnRH analogue administration, or at peripheral-ovarian vein gradient, suggests no pituitary-ovarian axis involvement in VitD production or its direct ovarian production in lean and normoinsulinemic PCOS subjects.

Acromegaly and ultrasound: how, when and why?

BACKGROUND: Acromegaly is a rare disease caused by an excess of growth hormone and insulin-like growth factor 1. It is usually diagnosed because of typical signs such as macroglossia, acral enlargement, jaw prognathism and malocclusion. Systemic complications are a major cause of morbidity and mortality in acromegaly, and many patients remain undiagnosed for several years. Increased ultrasound (US) application in the general population, and including among acromegaly patients, has revealed many suggestive features which, taken together with clinical suspicion, could induce suspicion of this disease. PURPOSE: This review describes main US features in acromegaly. Echocardiography shows a typical cardiomyopathy, characterized by left ventricular hypertrophy, diastolic and systolic dysfunction, aortic and mitral regurgitation, and increased aortic root diameters. US preclinical markers of atherosclerosis, such as intima media thickness (IMT), seem also to be impaired. Visceromegaly and increased organ stiffness are other features of acromegaly, including enlarged prostate, kidneys, liver, and thyroid. In addition, other US findings are: renal cysts, micronephrolithiasis, impairment of renal haemodynamic parameters, gallstones and gallbladder polyps, hepatic steatosis, thyroid nodules, multinodular goiter, and polycystic ovaries. Musculoskeletal US findings are increased cartilage thickness, impaired density and elasticity of bones, nerve enlargement, carpal and cubital tunnel syndrome, and trigger finger. CONCLUSIONS: Acromegaly patients frequently present systemic complications and a diagnostic delay. US features of acromegaly are not specific, but could potentially have a key role in early detection of the disease in the presence of typical clinical features.

Sleep disorders and cognitive dysfunction in acromegaly.

PURPOSE: In the general population, sleep disorders are associated with an increased risk of cognitive impairment. The prevalence of sleep disorders, such as sleep apnea, in acromegalic patients is higher than in the general population, and they may have additional risk of cognitive impairment due to acromegaly treatment and comorbidities. We aim to study the relationship between sleep disturbances and cognitive dysfunction in a group of acromegalic patients. METHODS: We studied 67 consecutive acromegalic patients. We performed a neurocognitive assessment and patients completed the Acromegaly Quality of Life Questionnaire (AcroQoL), Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index. RESULTS: Of the 67 acromegaly patients in the study, 38.8% were male and median age at the neurological examination was 56 (IQR 48, 65). Approximately 6-10% of patients had impaired cognitive assessment, depending on the test. In linear regression models adjusted for age, sex, BMI, disease duration, and disease activity, poorer sleep quality was associated with lower global cognitive z-score (B = -0.03, 95% CI -0.06, -0.002). Daytime somnolence was associated with poorer physical AcroQoL sub-score (B = -0.04, 95% CI -0.08, -0.002). Sleep quality was associated with poorer overall AcroQoL (B = -0.03, 95% CI -0.05, -0.006), physical AcroQoL (B = -0.04, 95% CI -0.07, -0.005), psychological AcroQoL (B = -0.02, 95% CI -0.04, -0.001), and social AcroQoL (B = -0.02, 95% CI -0.04, -0.0009). CONCLUSIONS: In acromegaly patients, we found robust evidence that poor sleep quality is associated with poorer quality of life, and some evidence that it is associated with poorer cognitive function.

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.

Pre-operative Very Low Calorie Ketogenic Diet (VLCKD) vs. Very Low Calorie Diet (VLCD): Surgical Impact.

BACKGROUND: Pre-operative diet may play an important role as far as patients' fitness for surgery, post-operative outcomes, and successful weight loss. Our aim was to compare surgical outcome and weight loss in two groups of patients who were offered two different pre-operative kinds of diet: very low calorie diet (VLCD) and very low calorie ketogenic diet (VLCKD). METHODS: Patients candidate for bariatric surgery (laparoscopic sleeve gastrectomy) were registered and assessed according to pre- and post-diet BMI, operative time, hospital stay, drainage output, and hemoglobin (Hb) levels. Patients' preference influenced the type of diet. RESULTS: From January to December 2016, 178 patients (139 F and 39 M) were enrolled in this study. The mean age was 43 years. In total, 72 patients were on VLCKD while 106 patients on VLCD. Pre-diet mean BMI was 46.3 ± 6.3 kg/m2 for VLCKD group and 43.1 ± 6.9 kg/m2 for VLCD group, while immediately pre-op BMI were 43.9 ± 5.9 kg/m2 and 41.9 ± 6.8 kg/m2, respectively. Drainage output and hemoglobin levels after surgery resulted significantly correlated with diet induced BMI reduction (141.2 ± 75.8 vs. 190.7 ± 183.6 ml, p = 0.032; 13.1 ± 1.2 vs. 12.7 ± 1.5 g/l, p = 0.04). The percentage of patients requiring a hospital stay longer than anticipated (> 3 days) was 2.8% in the VLCKD group and 10.4% in the VLCD group (p = 0.048). CONCLUSIONS: In our experience, VLCKD showed better results than VLCD on surgical outcome, influencing drainage output, post-operative hemoglobin levels, and hospital stay.

Guidelines versus real life practice: the case of colonoscopy in acromegaly.

PURPOSE: The aim of this study is to investigate guideline application and colonoscopy findings in real-life practice in acromegaly. METHODS: We conducted a retrospective observational non-interventional and cross-sectional analysis on 146 patients with acromegaly (ACRO) referred to our clinic. We evaluated colonoscopy data, focusing on the correlation between colonoscopy findings and hormonal/metabolic values. RESULTS: The total number of colonoscopies performed in ACRO patients increased from 6 in the period 1990-1994 to 57 in the period 2010-2014. Colonoscopy procedures were performed according to guidelines in 25% of ACRO patients at diagnosis, 51% at follow-up and 11% globally (both at diagnosis and follow-up). Among the 146 ACRO patients, 68% were subjected to at least one colonoscopy and in 32% of the cases a polyp was detected during the procedure. The presence of polyps was significantly associated with mean levels of growth hormone (GH), insulin-like growth factor 1 (IGF-1), fasting glucose and insulin levels (p < 0.05). Polyps were detected in 48% of untreated patients and in 26% of patients under treatment for acromegaly (p = 0.04). The general risk of polyps and adenomatous polyps in ACRO patients was higher compared to the control population of Veneto Region, Italy (odds ratio 1.33 and 1.16, respectively). No cancerous polyps were detected in our analysis. CONCLUSION: In real-life practice, adherence to ACRO colonoscopy clinical guidelines was lower than expected. Among patients who underwent colonoscopy, the prevalence of colon polyps was higher for ACRO patients, suggesting the need for new strategies to ensure adherence to colonoscopy guidelines.

Innovative clinical pathways for obese pregnant women: design and feasibility of the Padua project (North-Eastern Italy).

BACKGROUND: Obesity during pregnancy can adversely affect the wellbeing of the mother and the newborn, as well as the latter's long-term health. Preconception counseling, careful prenatal management, and strict follow-up during pregnancy are, therefore, essential for obese fertile women in order to prevent the negative effects of obesity. METHODS: In this setting, we developed a project that consisted in creating an integrated network of primary, secondary, and tertiary care providers and designing new clinical pathways for managing pregnancy in obese women. RESULTS: Two distinct pathways were devised: a Pre-Gestational Pathway for programming a pregnancy in obese women; and a Gestational Pathway for the clinical management of their pregnancy. DISCUSSION: Judging from the preliminary results of our study, the latter (Gestational) pathway seems to be successful, since there has been a gradual increase in the number of women using it, and these women have reported having no difficulty in accessing the services involved. It is noteworthy that immigrant women (who accounted for 60% of the women using the pathway) also reported no access issues. The pre-gestational pathway was very little used, however, accounting for only 2% of the appointments made with the services involved. In conclusion, the key to success in managing pregnancy in obese women lies in sharing the various different health care competences required and taking the local resources into account. The prevention of obesity in women of fertile age remains the main problem, however, and further efforts are needed in this setting.

Carbohydrates and insulin resistance in clinical nutrition: Recommendations from the ESPEN expert group.

Growing evidence underscores the important role of glycemic control in health and recovery from illness. Carbohydrate ingestion in the diet or administration in nutritional support is mandatory, but carbohydrate intake can adversely affect major body organs and tissues if resulting plasma glucose becomes too high, too low, or highly variable. Plasma glucose control is especially important for patients with conditions such as diabetes or metabolic stress resulting from critical illness or surgery. These patients are particularly in need of glycemic management to help lessen glycemic variability and its negative health consequences when nutritional support is administered. Here we report on recent findings and emerging trends in the field based on an ESPEN workshop held in Venice, Italy, 8-9 November 2015. Evidence was discussed on pathophysiology, clinical impact, and nutritional recommendations for carbohydrate utilization and management in nutritional support. The main conclusions were: a) excess glucose and fructose availability may exacerbate metabolic complications in skeletal muscle, adipose tissue, and liver and can result in negative clinical impact; b) low-glycemic index and high-fiber diets, including specialty products for nutritional support, may provide metabolic and clinical benefits in individuals with obesity, insulin resistance, and diabetes; c) in acute conditions such as surgery and critical illness, insulin resistance and elevated circulating glucose levels have a negative impact on patient outcomes and should be prevented through nutritional and/or pharmacological intervention. In such acute settings, efforts should be implemented towards defining optimal plasma glucose targets, avoiding excessive plasma glucose variability, and optimizing glucose control relative to nutritional support.

Heart rate variability is reduced in acromegaly patients and improved by treatment with somatostatin analogues.

BACKGROUND: Cardiovascular complications, including arrhythmias and cardiac sudden death, are the most common causes of enhanced mortality in acromegaly. However, few data are available on cardiac autonomic functions and sympathovagal balance in acromegalic patients. OBJECTIVE: The aim of this study was to investigate both the time and frequency domain parameters of Heart Rate Variability (HRV), in order to characterize the cardiac autonomic functions in patients affected by acromegaly. This study correlated anthropometric, metabolic, echocardiographic parameters and blood pressure with those relating to HRV, to identify the main factors responsible for the HRV related alterations possibly present. We also aimed to analyze the effects of the treatment with somatostatin analogues (SSAs) on HRV. MATERIALS AND METHODS: This study enrolled 47 acromegalic patients (23 males, age 49.1 ± 13.5 years) and 37 (13 males) age matched (52.3 ± 13.3 years) healthy subjects. All participants underwent 12-lead 24 h ECG Holter recordings and a HRV analysis of the ECG tracings was performed. The parameters obtained from the time domain analysis of HRV included pNN50, SDNN, SDNN index, SDANN and RMSSD. The power spectral analysis of HRV was obtained by summing powers of the LF (low frequency) and the HF (high frequency) band. Sympathovagal balance was estimated by calculating the LF/HF ratio during 24 h and 15 min of clinostatism. The HRV of 28 acromegalic patients was studied before and after SSAs treatment. RESULTS: Acromegalic patients showed significantly lower SDNN and SDANN compared to controls. Diabetic and non-diabetic acromegalic patients showed decreased SDNN and SDANN, when compared to healthy subjects. Diabetic acromegalic patients had a lower LF/HF ratio during 24 h when compared to non-diabetic acromegalic patients. Similar results were obtained analyzing patients affected by acromegaly and impaired glucose tolerance. SDNN and SDANN were lowered by hypertension in the acromegalic population, when compared to controls, and hypertensive acromegalic patients also displayed a decreased LF/HF ratio during 24 h when compared to normotensive acromegalic subjects. Patients with ventricular arrhythmias in Lown classes 3-5 showed a decreased SDANN compared to patients in Lown class 0-2. The treatment with SSAs was able to ameliorate all the time domain parameters of HRV, without altering the 24 h LF/HF ratio. CONCLUSION: Cardiac autonomic functions and sympathovagal balance are altered in patients affected by acromegaly and could be ameliorated by SSAs therapy. HRV analysis allows an estimation of the autonomic sympathovagal balance and may be a useful clinical tool for the cardiac risk stratification in acromegalic patients.