Efficacy of multivitamin support following bariatric surgery in patients with obesity: a prospective observational study.

PURPOSE: Bariatric surgery (BS), an effective treatment for severe obesity and its comorbidities, may result in micronutrient and vitamin deficiencies. This monocentric prospective observational study aimed at evaluating the efficacy of a specifically designed vitamin/mineral formula (Bariatrifast, BIOITALIA S.r.l., Italy) for preventing and treating micronutrient deficiencies in patients submitted to BS. METHODS: Twenty patients with severe obesity (mean weight and BMI: 123.5 kg (range 88-174) and 43.3 kg/m2 (range 37-54) respectively) underwent BS (10 vertical sleeve gastrectomy VSG, 10 Roux-en-Y gastric bypass, RYGB). The mean age was 49.9 years (range 27-68). After a presurgical visit (V0), follow-up visits were performed at 1, 3, 6 and 12 months after surgery (V1-V4). Recorded data included weight, height and BMI. A complete blood count, measurement of ferritin, folic acid, vitamin B12, ionized calcium, 25 OH vitamin D, parathyroid hormone (PTH) were obtained. Following BS, patients started the daily oral multivitamin and mineral supplement. RESULTS: All patients achieved a significant weight loss (mean - 34.7 ± 11.8 kg). No deficiencies of various vitamins/micronutrients were detected during the entire study period. The serum concentrations of vitamin B12, 25-OH Vitamin D and folic acid increased over the follow-up period compared with V0 (mean increase 243 ng/L, 23 µg /L, 8 µg/L, respectively). Compared to RYGB, patients who underwent sleeve gastrectomy showed higher levels of 25-OH vitamin D at V2, V3 and V4 (all p < 0.05), and higher levels of Vitamin B12 and folic acid at V4 (p < 0.05 and p < 0.005, respectively). No adverse events were reported. CONCLUSION: Following VSG or RYGB, Bariatrifast administration was associated with normal values of essential micronutrients, and it was well-tolerated without evidence of gastrointestinal side effects. Clinical Trial Registration ClinicalTrials.gov, identifiers NCT06152965.

Eating disorders and emotional dysregulation are associated with insufficient weight loss after bariatric surgery: a 1-year observational follow-up study.

PURPOSE: Subjects with obesity, especially those seeking bariatric surgery, exhibit high rates of mental disorders and marked psychopathological traits. The primary objective of this prospective, non-interventional study was to investigate whether the presence of different psychiatric disorders, attention deficit/hyperactivity disorder (ADHD) symptomatology and emotional dysregulation influenced weight loss at 1-year follow-up after surgery. METHODS: Subjects consecutively referred for pre-surgical evaluation at the Obesity Center of Pisa University Hospital were recruited. Psychiatric diagnoses were made through the Mini-International Neuropsychiatric Interview (MINI) and ADHD symptomatology was assessed with the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS). Emotional dysregulation was investigated through the WRAADDS and self-report questionnaires. After surgery, weight and obesity-related comorbidities were monitored during follow-up. RESULTS: Of the 99 participants recruited, 76 underwent surgery and 65 could be reevaluated 1 year after surgery. Subjects with insufficient weight loss (excess body mass index loss ≤ 53%, n = 15) had more frequent lifetime binge eating disorder (BED) and BED-mood disorders comorbidity than subjects with favorable post-surgical outcome. Additionally, they scored higher on both physician-administered and self-report scales assessing emotional dysregulation, which represents a nuclear symptom of ADHD in adults. At the logistic regression analysis, older age, higher preoperative excess body mass index and greater affective instability were predictors of reduced weight loss at 1-year follow-up. CONCLUSION: Emotional dysregulation seems to be associated with a worse outcome after bariatric surgery. Further studies with larger samples and longer follow-up are needed to confirm the influence of different psychiatric disorders and psychopathological traits on post-surgical outcome. LEVEL OF EVIDENCE: V, prospective descriptive study.

Obesity, Hyperfiltration, and Early Kidney Damage: A New Formula for the Estimation of Creatinine Clearance.

CONTEXT: Glomerular hyperfiltration may represent a direct pathogenetic link between obesity and kidney disease. The most widely used methods to estimate creatine clearance such as Cockroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) have not been validated in subjects with obesity. OBJECTIVE: The performance of prediction formulas was compared with measured creatinine clearance (mCrCl) in subjects with obesity. METHODS: The study population included 342 patients with obesity (mean BMI 47.6 kg/m2) without primary kidney disease. A urine collection was performed over 24 hours for measurement of CrCl. RESULTS: mCrCl increased with body weight. The CG formula showed an overestimation at high CrCl, whereas an underestimation resulted from CKD-EPI and MDRD. To improve the accuracy of estimated CrCl (eCrCl), a new CG-based formula was developed:53+0.7×(140-Age)×Weight/(96xSCr)×(0.85iffemale)A cut-off point for BMI of 32 kg/m2 was identified, at which the new formula may be applied to improve eCrCl. CONCLUSION: In patients with obesity the glomerular filtration rate increases with body weight, and it is associated with the presence of albuminuria, suggesting an early kidney injury. We propose a novel formula that improves the accuracy of eCrCl to avoid missed diagnoses of hyperfiltration in patients with obesity.

Circulating Levels of MiRNAs From 320 Family in Subjects With Lipodystrophy: Disclosing Novel Signatures of the Disease.

Lipodystrophy (LD) indicates a group of rare disorders, with generalized or partial loss of white adipose tissue (WAT) often associated with metabolic derangements. Heterogeneity/wide spectrum of the disease and lack of biomarkers make diagnosis often difficult. MicroRNAs are important to maintain a correct WAT function and WAT is a source of circulating miRNAs (cmiRs). miRNAs from 320 family were previously detected in the WAT and variably associated to the metabolic syndrome. Our aim was then to investigate if LD can result in altered abundance of cmiRs-320. We collected samples from a cohort of LD subjects of various subtypes and from age matched controls. Use of quantitative PCR determined that cmiRs- 320a-3p, 320b, 320c, 320e are upregulated, while 320d is downregulated in LD. CmiRs-320 power as classifiers was more powerful in the most extreme and defined forms of LD, including the generalized and the Dunnigan subtypes. cmiR-320a-3p showed significant inverse relationships with plasma leptin (P < 0.0001), typically low in LD. The hepatic enzymes gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the marker of inflammation C-reactive protein (CRP) were inversely related to cmiR 320d (P < 0.05, for CRP and GGT; P < 0.01, for AST and ALT). Gene ontology analysis revealed cell-cell adhesion as a process regulated by 320 miRNAs targets, thus disclosing a novel route to investigate origin of WAT loss/dysfunction. In conclusion, cmiRs-320 constitute novel biomarkers of LD, abundance of miR320a-3p is inversely associated to indicators related to WAT function, while downregulation of cmiR-320d predicts an altered hepatic profile and higher inflammation.

Prevalence of mood, panic and eating disorders in obese patients referred to bariatric surgery: patterns of comorbidity and relationship with body mass index.

PURPOSE: We aimed at investigating the lifetime prevalence of mood, eating and panic disorders in a large sample of obese patients referred to bariatric surgery. We also explored the patterns of psychiatric comorbidity and their relationship with Body Mass Index (BMI). METHODS: The sample was composed of patients consecutively referred for pre-surgical evaluation to the Obesity Center of Pisa University Hospital between January 2004 and November 2016. Clinical charts were retrieved and examined to obtain sociodemographic information, anthropometric variables and lifetime psychiatric diagnoses according to DSM-IV criteria. RESULTS: A total of 871 patients were included in the study; 72% were females, and most patients had BMI ≥ 40 kg/m2 (81%). Overall, 55% of the patients were diagnosed with at least one lifetime psychiatric disorder. Binge eating disorder (27.6%), major depressive disorder (16%), bipolar disorder type 2 (15.5%), and panic disorder (16%) were the most common psychiatric diagnoses. Mood disorders showed associations with panic disorder (OR = 2.75, 95% CI = 1.90-3.99, χ2 = 41.85, p = 0.000) and eating disorders (OR = 2.17, 95% CI 1.64-2.88, χ2 = 55.54, p = 0.000). BMI was lower in patients with major depressive disorder (44.9 ± 7.89) than in subjects without mood disorders (46.75 ± 7.99, padj = 0.017). CONCLUSION: Bariatric patients show high rates of psychiatric disorders, especially binge eating and mood disorders. Longitudinal studies are needed to explore the possible influence of such comorbidities on the long-term outcome after bariatric surgery. LEVEL OF EVIDENCE: V, cross sectional descriptive study.

Prevalence and psychiatric comorbidities of night-eating behavior in obese bariatric patients: preliminary evidence for a connection between night-eating and bipolar spectrum disorders.

PURPOSE: The co-occurrence of obesity, eating and mood disorders has been frequently reported in clinical and epidemiological settings. This study aimed to explore the prevalence of night-eating obese patients referred for bariatric surgery and to identify associated psychopathology and psychiatric comorbidity. METHODS: The sample was composed of 121 obese patients consecutively enrolled between November 2010 and May 2012 during psychiatric evaluations for bariatric intervention. Clinical features and psychiatric diagnoses were collected. Night-eating was investigated through the administration of the Night-eating Questionnaires (NEQ) and was defined as the presence of self-reported evening hyperphagia and/or nocturnal ingestions. Binge-eating and purging behaviors and general psychopathology were respectively assessed using the Bulimic Investigatory Test, Edinburgh and the Symptom Checklist-90-Revised. RESULTS: Night-eating was reported by twenty subjects (16.5%). Patients with night-eating behavior were significantly more frequently diagnosed with bipolar spectrum disorders and with comorbid eating and mood disorders in comparison with other patients. Night-eating patients showed significantly more binging/purging behaviors and greater severity of somatization, obsessive-compulsive symptoms, phobic anxiety, psychoticism and sleep disorders. Patients with bipolar disorder type 1 or 2 scored significantly higher than those without mood disorders at NEQ total score, mood/sleep and nocturnal ingestions subscales, but also scored significantly higher than other patients with mood disorders at the latter subscale. CONCLUSION: Patients with evening hyperphagia and/or nocturnal ingestions should be carefully evaluated to detect possible bipolar spectrum disorders and other eating disorders. Prompt management of these conditions should be provided before bariatric interventions. LEVEL OF EVIDENCE: V, cross-sectional descriptive study.

Ophthalmologic evaluation of severely obese patients undergoing bariatric surgery: A pilot, monocentric, prospective, open-label study.

PURPOSE: The aim of this study was to investigate the pathogenic role of obesity on blinding eye diseases in a population of severely obese patients with no history of eye diseases, and to verify whether weight loss induced by bariatric surgery may have a protective effect. METHODS: This was a pilot, monocentric, prospective, and open label study conducted at the University Hospital of Pisa. Fifty-seven severely obese patients with a mean body mass index value of 44.1 ± 6 kg/m2 were consecutively recruited and received a complete ophthalmological evaluation and optical coherence tomography. Twenty-nine patients who underwent gastric bypass were evaluated also 3 months, and 1 year after surgery. RESULTS: At baseline, blood pressure value were directly and significantly related to intraocular pressure values (p<0.05, R = 0.35). Blood pressure values were also significantly and inversely related to retinal nerve fiber layer thickness, particularly in the temporal sector (RE p<0.05 r-0.30; LE p<0.01, R = -0.43). Moreover, minimum foveal thickness values were significantly and inversely associated with body mass index (RE p<0.02, R = -0.40; LE p<0.02, R = -0.30). A significant reduction of body mass index (p<0.05) and a significant (p<0.05) improvement of blood pressure was observed three months and one year after gastric bypass, which were significantly associated with an increase in retinal nerve fiber layer thickness and minimum foveal thickness values in both eyes (p<0.05). CONCLUSIONS: The results of this study suggest that obese patients may have a greater susceptibility to develop glaucomatous optic nerve head damage and age-related macular degeneration. Moreover, weight reduction and improvement of comorbidities obtained by bariatric surgery may be effective in preventing eye disease development by improving retinal nerve fiber layer and foveal thickness.

Serum IGF-binding protein 2 (IGFBP-2) concentrations change early after gastric bypass bariatric surgery revealing a possible marker of leptin sensitivity in obese subjects.

PURPOSE: Expression of IGFBP-2 in mice is regulated by leptin. Over-expression of IGFBP-2 is associated with reduced caloric intake and resistance to weight gain. Hormonal variations contributing to weight loss occur very early after bariatric surgery but have not been fully elucidated. We evaluated IGFBP-2 serum changes after bariatric surgery and their relationship with leptin variations to test the hypothesis that an increase of leptin sensitivity may explain some of the effects of gastric bypass. METHODS: This is a historical prospective study. Fifty-one obese patients (41 women e 10 men), 9 non-obese surgical controls and 41 lean matched controls were studied. Serum IGFBP-2 and leptin were measured after bariatric bypass surgery at various time points up to 18 months, after non-bariatric laparoscopic surgery in a control group, and in lean matched controls. RESULTS: Compared to lean controls, serum IGFBP-2 levels were lower in obese patients. After gastric bypass, IGFBP-2 significantly increased at 3 days and became normal before the occurrence of relevant changes in body weight, remaining stable up to 18 months after surgery. IGFBP-2/leptin ratio increased early after surgery and became normal after one year. CONCLUSIONS: After gastric bypass, serum IGFBP-2 increases in a window of time when variations of hormones mediating the effects of bariatric surgery occur. Our results suggest that IGFBP-2, a leptin-regulated protein, may be an in-vivo marker of leptin action. If this is the case, an early improvement of leptin sensitivity might contribute to the anorectic effect of gastric bypass.

24-Hour ambulatory blood pressure levels and control in a large cohort of adult outpatients with different classes of obesity.

Effective and sustained blood pressure (BP) control in hypertensive patients with moderate-to-severe obesity is often difficult to achieve. We evaluated clinic, 24h, day-time and night-time systolic/diastolic BP levels and control in a large cohort of adult outpatients with different classes of obesity. A single center, prospective, cohort study was conducted at Hypertension Unit, Division of Cardiology, Sant'Andrea Hospital, Rome Italy. All BP measurements were performed and BP thresholds were set according to guidelines. Study population was stratified according to BMI. We included 4,766 individuals (women 48.6%, age 60.3 ± 11.6 years, clinic BP 143.8 ± 18.2/90.9 ± 12.3 mmHg, 24h BP 130.2 ± 13.3/79.1 ± 9.5 mmHg), among whom 36.0% had normal weight, 43.5% were overweight, 15.7% had class I, and 4.8% class II/III obesity. Obese outpatients had higher prevalence of risk factors, and were treated more frequently and with more antihypertensive drugs than those with normal body weight. Obese outpatients showed higher systolic BP levels at all BP measurements, mostly 24h and night-time periods, than those observed in normal weight outpatients. BMI resulted significantly related with clinic (r = 0.053; P < 0.001), 24h (r = 0.098; P < 0.001) and night-time systolic BP (r = 0.126; P < 0.001), and left ventricular mass indexed by height^2.7 (r = 0.311; P < 0.001). BMI was also negatively and independently associated with predefined BP goals at all types of BP measurements. Obesity was associated with higher systolic BP levels during the entire 24h period and increased left ventricular mass. These effects were independently observed, even after correction for major cardiovascular risk factors and comorbidities, as well as the number and type of antihypertensive drug classes.

Liver Enlargement Predicts Obstructive Sleep Apnea-Hypopnea Syndrome in Morbidly Obese Women.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is frequently present in patients with severe obesity, but its prevalence especially in women is not well defined. OSAHS and non-alcoholic fatty liver disease are common conditions, frequently associated in patients with central obesity and metabolic syndrome and are both the result of the accumulation of ectopic fat mass. Identifying predictors of risk of OSAHS may be useful to select the subjects requiring instrumental sleep evaluation. In this cross-sectional study, we have investigated the potential role of hepatic left lobe volume (HLLV) in predicting the presence of OSAHS. OSAHS was quantified by the apnea/hypopnea index (AHI) and oxygen desaturation index in a cardiorespiratory inpatient sleep study of 97 obese women [age: 47 ± 11 years body mass index (BMI): 50 ± 8 kg/m2]. OSAHS was diagnosed when AHI was ≥5. HLLV, subcutaneous and intra-abdominal fat were measured by ultrasound. After adjustment for age and BMI, both HLLV and neck circumference (NC) were independent predictors of AHI. OSAHS was found in 72% of patients; HLLV ≥ 370 cm3 was a predictor of OSAHS with a sensitivity of 66%, a specificity of 70%, a positive and negative predictive values of 85 and 44%, respectively (AUC = 0.67, p < 0.005). A multivariate logistic model was used including age, BMI, NC, and HLLV (the only independent predictors of AHI in a multiple linear regression analyses), and a cut off value for the predicted probability of OSAHS equal to 0.7 provided the best diagnostic results (AUC = 0.79, p < 0.005) in terms of sensitivity (76%), specificity (89%), negative and positive predictive values (59 and 95%, respectively). All patients with severe OSAHS were identified by this prediction model. In conclusion, HLLV, an established index of visceral adiposity, represents an anthropometric parameter closely associated with OSAHS in severely obese women.

Prevalence and determinants of left ventricular diastolic dysfunction in obese subjects and the role of left ventricular global longitudinal strain and mass normalized to height.

BACKGROUND: Left ventricular (LV) diastolic dysfunction (DD) is a frequent finding in obesity and may predispose to the development of heart failure (HF). However, no data are available on the prevalence of DD after the introduction of the 2016 Recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging. METHODS AND RESULTS: To assess the impact of the new Recommendations on the prevalence of DD and on their clinical and echocardiographic correlates in obesity, a prospective study was performed in 588 subjects with an ejection fraction (EF) ≥50% and no history of HF either obese (n = 402; mean age: 47 ± 12 years; women 71%; body mass index [BMI]: 44 ± 8 kg/m2 ), overweight (n = 86; BMI: 28 ± 1 kg/m2 ), or with a normal weight (n = 100; BMI: 22 ± 2 kg/m2 ). All subjects underwent an echocardiographic and Doppler study, including the assessment of global longitudinal strain (GLS). DD occurred in 19% of obese patients, 12% of overweight subjects, and 2% of normal weight subjects. We used multivariable logistic analysis to assess the risk of DD. In patients with BMI ≥30 kg/m2 , LV mass normalized to height (2.7) (OR: 1.04, P = .0028), and GLS (OR: 0.85, P = .0032) were associated with an increased risk of DD followed by EF (OR: 0.91, P = .045), diabetes (OR: 1.91, P = .065), and systolic blood pressure (OR: 1.02, P = .076). CONCLUSION: These results show that DD is highly prevalent among obese subjects and impairment of longitudinal systolic mechanics, as reflected by GLS reduction, and LV mass normalized to height are major independent predictors of DD in this patients' population.

[Consensus document and recommendations for the prevention of cardiovascular disease in Italy - 2018]. / Documento di consenso e raccomandazioni per la prevenzione cardiovascolare in Italia 2018.

Cardiovascular prevention represents a cornerstone of modern strategies to reduce the burden of cardiovascular disease. It is of key importance to prevent cardiovascular diseases and associated events, not only to reduce morbidity and mortality, but also to increase the years of wellness in the aging population and to make the growing socio-economic burden imposed by cardiovascular events more sustainable.The current approach to prevention is based on an integrated use of effective lifestyle measures and, whenever appropriate, of antihypertensive and antidiabetic drugs, lipid-lowering agents and antiplatelet drugs.Given that population characteristics, in terms of ethnicity, demography and lifestyle habits, and healthcare system organizations differ among countries, international guidelines are not always applicable to specific countries and, often, are difficult to translate into daily clinical practice.In order to afford the specific features of Italy, 10 Scientific Societies and Research Institutions, mostly involved in preventive strategies, contributed to the present Italian consensus document, which includes brief, practical recommendations to support the preventive actions within the physician community and the general practice setting.

Weight Loss and Variation of Levothyroxine Requirements in Hypothyroid Obese Patients After Bariatric Surgery.

BACKGROUND: Obesity and hypothyroidism are both common disorders within the general population. Obese hypothyroid subjects require higher doses of levothyroxine (LT4) compared with normal weight individuals. Previous studies on the effects of bariatric surgery on LT4 dose requirements in hypothyroid subjects have provided conflicting results. The aim of this study was to evaluate the LT4 requirements in a group of obese subjects with acquired hypothyroidism, before and after weight loss achieved by bariatric surgery. METHODS: Ninety-three obese hypothyroid subjects (mean age = 48 ± 9 years; mean body mass index = 45.9 ± 5.6 kg/m(2)), were evaluated before and 28 ± 8 months after bariatric surgery. Changes in the LT4 dose, anthropometric measures, and hormone values were evaluated. In 20 patients, data of body composition, assessed by dual energy X-ray absorptiometry, were also analyzed. RESULTS: On average, after weight loss, a significant reduction of the total dose of LT4 was documented (from 130.6 ± 48.5 to 116.2 ± 38.6 µg/day; p < 0.001). The LT4 dose had to be reduced in 47 patients, was unchanged in 34, and had to be increased in 12 patients affected by autoimmune thyroiditis. Reduction of the LT4 dose was proportional to reduction of the lean body mass. CONCLUSIONS: The weight loss achieved with modern surgical bariatric procedures is associated with a reduction of LT4 requirements in most hypothyroid subjects, which appears to be related to a decrease of the lean body mass. Occasionally, a concurrent decline of residual thyroid function, as it occurs in autoimmune thyroiditis, can counteract this phenomenon and eventually produce an increase of LT4 needs. It is believed that during the weight loss phase that follows bariatric surgery, there is no need for preventive adjustments of the LT4 dose, but serum thyroid hormones and thyrotropin should be periodically monitored in order to detect possible variations of LT4 requirements and to allow proper corrections of the therapy.

Chronic Renin-Angiotensin System (RAS) Blockade May Not Induce Hypotension During Anaesthesia for Bariatric Surgery.

The use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) for the treatment of hypertensive obese patients is steadily increasing. Some studies have reported that the use of these drugs was associated with an increased risk of hypotensive episodes, during general anaesthesia. The number of bariatric procedures is also increasing worldwide, but there is a lack of studies investigating the hypotensive effect of renin-angiotensin system (RAS) blockers in severely obese patients during general anaesthesia for bariatric surgery. The aim of this pilot study was to evaluate hemodynamic changes induced by general anaesthesia in obese patients chronically treated with ACE-I or ARB compared to a control group not treated with antihypertensive therapy. Fourteen obese subjects (mean body mass index (BMI) 47.5 kg/m(2)) treated with ACE-I or ARB and twelve obese (mean BMI 45.7 kg/m2) controls not treated with antihypertensive therapy underwent general anaesthesia to perform laparoscopic bariatric surgery. Systolic blood pressure, diastolic blood pressure, and heart rate were monitored continuously and registered at different time points: T0 before induction, then at 2, 5, 7, 10, 15, 20, 30, 60, 90, 120, and 150 min after induction, and the last time point taken following recovery from anaesthesia. A progressive reduction of both systolic and diastolic blood pressure values was observed without significant differences between the two groups. A similar trend of heart rate values was observed. In conclusion, our pilot study suggests that RAS blockers may be continued during the perioperative period in patients undergoing bariatric surgery, without increasing the risk of hypotensive episodes.

Prevalence of left ventricular hypertrophy and determinants of left ventricular mass in obese women.

BACKGROUND: Obesity is frequently associated with left ventricular hypertrophy (LVH), a condition leading to an increased cardiovascular risk. AIM: The objective of this study was to evaluate the prevalence of LVH in a cohort of obese women, with a main focus on the anthropometric and clinical parameters that are associated with an increased left ventricular mass (LVM). METHODS: The study was performed in 166 obese female patients. LVM was measured by echocardiography. The influence of various parameters on LVM was assessed by multivariate analysis. RESULTS: The prevalence of LVH was drastically different depending on the type of indexed LVM, being 19.9% when the LVM was indexed for body surface area and 72.3% when indexed for height. Age, duration of obesity, weight, waist-to-hip ratio, pulse pressure and hypertension retained an independent direct correlation with the LVM, explaining 39.6% of the overall LVM variability. Among the parameters of the metabolic syndrome, the increase in blood pressure was the main determinant of increased LVM. CONCLUSIONS: By using allometric indexation of LVM for height, the results of our study indicate a high prevalence of LVH in a cohort of obese women. Hypertension, pulse pressure, age, duration of obesity, bodyweight and fat distribution, expressed as waist-to-hip ratio, predict 40% of LVM variation.

Xenon anesthesia reduces TNFα and IL10 in bariatric patients.

BACKGROUND: Anesthesia is able to modulate the balance between proinflammatory and anti-inflammatory cytokine production during surgery. The aim of this study is to assess the effect of three anesthesia approaches, total intravenous anesthesia (TIVA), inhalation anesthesia, and xenon anesthesia, on sieric levels of nitric oxide (NO), IL6, IL10, and TNFα in obese patients undergoing Roux-en-Y laparoscopic gastric bypass. METHODS: Thirty adult morbidly obese patients (BMI > 35) scheduled for Roux-en-Y laparoscopic gastric bypass were randomly recruited and allocated to TIVA (N = 10), inhalation anesthesia (SEV, N = 10), and xenon anesthesia (XE, N = 10). Exclusion criteria were ASA IV, age <18 or >60 years, and Mallampati IV. Opioid dosage and ventilation parameters were standardized. Sieric levels of NO, IL6, IL10, and TNFα were assessed at T0 (before induction of anesthesia), T1 (end of surgery), and T2 (12 h after the end of surgery). We compared the relative cytokine level variations (delta) at T1 and T2 and the cytokine exposure levels calculated as the area under the curve (AUC) between T0 and T2 in the XE and non-XE (SEV + TIVA) groups. RESULTS: At T1, we found a significant ΔIL10 (reduction) and ΔTNFα (reduction) between XE and SEV (p < 0.05) and XE and TIVA (p < 0.05) groups. At T2, ΔIL10 was still significant. Furthermore, we found a reduced AUC value for TNFα in the XE group. CONCLUSIONS: Xenon anesthesia seems able to inhibit postoperative proinflammatory cytokine imbalance in morbidly obese patients undergoing Roux-en-Y laparoscopic gastric bypass; the reduced ΔTNFα at T1 and the reduced global exposition to TNFα in the XE group may explain the reduced ΔIL10 at T1 and T2.

Description of an AGPAT2 pathologic allelic variant in a 54-year-old Caucasian woman with Berardinelli-Seip syndrome.

A 54-year-old Italian female patient was admitted to our Department with the diagnosis of type 2 diabetes poorly controlled with insulin therapy. The patient was born by consanguineous parents (first degree cousins); she had acromegaloid features, diffuse lipoatrophy and muscular pseudo-hypertrophy since childhood. To confirm the clinical hypothesis of congenital generalized lipodystrophy (CGL) or Berardinelli-Seip syndrome, the sequences of AGPAT2 (encoding for 1-acyl-sn-glycerol-3-phosphate acyltransferase beta) and BSCL2 (encoding for seipin) candidate genes were analyzed. DNA analysis showed the presence of a homozygous mutation in exon 3 of the AGPAT2 gene (P112L). This is the first description of a Caucasian subject with CGL who carries the pathologic allelic variant P112L of the AGPAT2 gene.

Vascular generation of tumor necrosis factor-α reduces nitric oxide availability in small arteries from visceral fat of obese patients.

OBJECTIVES: The aim of this study was to assess whether small arteries from visceral fat of obese patients show a reduced nitric oxide (NO)-dependent relaxation, as compared with lean control subjects, focusing on the role of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. BACKGROUND: Visceral obesity is characterized by endothelial dysfunction. METHODS: Small arteries from 14 obese (body mass index 48.4 ± 11 kg/m(2)) and 14 control subjects (body mass index 24.9 ± 2 kg/m(2)), dissected after a visceral fat biopsy (laparoscopy), were evaluated on a pressurized micromyograph. Endothelium-dependent relaxation was assessed by acetylcholine. The NO availability, superoxide production, and inflammation were assessed by testing acetylcholine under the nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine methylester, tempol (superoxide scavenger), and infliximab (monoclonal anti-TNF-α antibody), respectively. The roles of nicotinamide adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase (iNOS) were assessed by their selective inhibitors apocynin and S-methylisothiourea (SMT), respectively. Vascular superoxide generation (dihydroethidium staining) protein expression of TNF-α and NOS isoforms (Western Blot) and TNF-α localization (immunohistochemistry) were assessed. RESULTS: Vessels from obese patients displayed a blunted relaxation to acetylcholine and a reduced inhibitory effect of N(ω)-nitro-L-arginine methylester. These alterations were normalized by tempol or infliximab while being partly ameliorated by apocynin and SMT. Vascular superoxide generation was increased (p < 0.01) in obese patients. This condition was abrogated by both tempol and infliximab and partly (p < 0.05 vs. control subjects) reduced by apocynin or SMT. Enhanced TNF-α and iNOS expression together with increased TNF-α localization in the vascular media were detected. CONCLUSIONS: Small arteries from visceral fat of obese patients are characterized by an increased TNF-α production, which reduces NO availability by promoting superoxide generation via nicotinamide adenine dinucleotide phosphate oxidase and iNOS activation.

Prevalence of endocrine diseases in morbidly obese patients scheduled for bariatric surgery: beyond diabetes.

BACKGROUND: Bariatric surgery allows stable body weight reduction in morbidly obese patients. In presurgical evaluation, obesity-related co-morbidities must be considered, and a multidisciplinary approach is recommended. Precise guidelines concerning the endocrinological evaluation to be performed before surgery are not available. The aim of this study was to evaluate the prevalence of common endocrine diseases in a series of obese patients scheduled for bariatric surgery. METHODS: We examined 783 consecutive obese subjects (174 males and 609 females) aged 18-65 years, who turned to the obesity centre of our department from January 2004 to December 2007 for evaluation before bariatric surgery. Thyroid, parathyroid, adrenal and pituitary function was evaluated by measurement of serum hormones. Specific imaging or supplementary diagnostic tests were performed when indicated. RESULTS: The overall prevalence of endocrine diseases, not including type 2 diabetes mellitus, was 47.4%. The prevalence of primary hypothyroidism was 18.1%; pituitary disease was observed in 1.9%, Cushing syndrome in 0.8%, while other diseases were found in less than 1% of subjects. Remarkably, the prevalence of newly diagnosed endocrine disorders was 16.3%. CONCLUSIONS: A careful endocrinological evaluation of obese subjects scheduled for bariatric surgery may reveal undiagnosed dysfunctions that require specific therapy and/or contraindicate the surgical treatment in a substantial proportion of patients. These results may help to define the extent of the endocrinological screening to be performed in obese patients undergoing bariatric surgery.