Search

Background: Roux-en-Y (RYGB) and one anastomosis gastric bypass (OAGB) represent two of the most used bariatric/metabolic surgery (BMS) procedures. Gut microbiota (GM) shift after bypass surgeries, currently understated, may be a possible key driver for the short- and long-term outcomes., Methods: Prospective, multicenter study enrolling patients with severe obesity, randomized between OAGB or RYGB. Fecal and blood samples were collected, pre- (T0) and 24 months postoperatively (T1). GM was determined by V3-V4 16S rRNA regions sequencing and home-made bioinformatic pipeline based on Qiime2 plugin and R packages., Objects: To compare OAGB vs RYGB microbiota profile at T1 and its impact on metabolic and nutritional status., Results: 54 patients completed the study, 27 for each procedure. An overall significant variation was detected in anthropometric and serum nutritional parameters at T1, with a significant, similar decrease in overall microbial alpha and beta diversity observed in both groups. An increase in relative abundances of Actinobacteria and Proteobacteria and a reduction of Bacteroidetes, no significant changes in Firmicutes and Verrucomicrobia, with an increase of the Firmicutes/Bacteroidetes ratio were observed., Conclusions: BMS promotes a dramatic change in GM composition. This is the first multicenter, RCT evaluating the impact of OAGB vs Roux-en-Y bypass on GM profile. The bypass technique per se did not impact differently on GM or other examined metabolic parameters. The emergence of slightly different GM profile postoperatively may be related to clinical conditions or may influence medium or long-term outcomes and as such GM profile may represent a biomarker for bariatric surgery's outcomes., (© 2024. The Author(s).)

The introduction of the term "Metabolic Steatotic Liver Disease" (MASLD) underscores the critical role of metabolic dysfunction in the development and progression of chronic liver disease and emphasizes the need for strategies that address both liver disease and its metabolic comorbidities. In recent years, a liver-focused perspective has revealed that altered endocrine function of the fatty liver is a key contributor to the metabolic dysregulation observed in MASLD. Due to its secretory capacity, the liver's increased production of proteins known as "hepatokines" has been linked to the development of insulin resistance, explaining why MASLD often precedes dysfunction in other organs and ultimately contributes to systemic metabolic disease. Among these hepatokines, fibroblast growth factor 21 (FGF21) and fetuin-A play central roles in regulating the metabolic abnormalities associated with MASLD, explaining why their dysregulated secretion in response to metabolic stress has been implicated in the metabolic abnormalities of MASLD. This review postulates why their modulation by GLP1-Ras may mediate the beneficial metabolic effects of these drugs, which have increased attention to their emerging role as pharmacotherapy for MASLD. By discussing the crosstalk between GLP1-Ras-FGF21-fetuin-A, this review hypothesizes that the possible modulation of fetuin-A by the novel GLP1-FGF21 dual agonist pharmacotherapy may contribute to the management of metabolic and liver diseases. Although research is needed to go into the details of this crosstalk, this topic may help researchers explore the mechanisms by which this type of pharmacotherapy may manage the metabolic dysfunction of MASLD.

The primary cause of the pandemic scale of type 2 diabetes (T2D) is the excessive and/or abnormal accumulation of adiposity resulting from a chronic positive energy balance. Any form of weight loss dramatically affects the natural history of T2D, favoring prevention, treatment, and even remission in the case of significant weight loss. However, weight regain, which is often accompanied by the recurrence or worsening of obesity complications such as T2D, is an inevitable biological phenomenon that is an integral part of the pathophysiology of obesity. This can occur not only after weight loss, but also during obesity treatment if it is not effective enough to counteract the physiological responses aimed at restoring adiposity to its pre-weight-loss equilibrium state. Over the past few years, many controlled and randomized studies have suggested a superior efficacy of bariatric surgery compared to conventional therapy in terms of weight loss, glycemic control, and rates of T2D remission. Recently, the therapeutic armamentarium in the field of diabetology has been enriched with new antihyperglycemic drugs with considerable efficacy in reducing body weight, which could play a pathogenetic role in the remission of T2D, not through the classical incretin effect, but by improving adipose tissue functions. All these concepts are discussed in this position statement, which aims to deepen the pathogenetic links between obesity and T2D, shift the paradigm from a "simple" interaction between insulin resistance and insulin deficiency, and evaluate the efficacy of different therapeutic interventions to improve T2D management and induce diabetes remission whenever still possible., (© 2024. The Author(s).)

Background: Type 2 diabetes (T2D) is a risk factor for female breast cancer (FBC). Obesity has also been associated with FBC, also depending on menopausal status. This study aimed to evaluate the impact of obesity and T2D on the development, aggressiveness, and invasiveness of FBC., Methods: Demographic, clinical, and histopathological data from 335 women with FBC were collected, and analyzed according to weight category (102 normal weight, 117 overweight, and 116 living with obesity) and the presence/absence of T2D., Results: Age at oncologic diagnosis was not statistically significantly different for body weight; women with overweight or obesity were more likely to have an oncologic diagnosis after menopause than normal weight ( p  < 0.001). The presence of overweight/obesity and T2D seemed to be associated with a higher incidence of metastasis, recurrence, and triple-negative breast cancer (TNBC) subtype ( p  < 0.001). Excess body weight was also associated with high histologic grade (G3) ( p  < 0.005)., Conclusions: These results confirm excess body weight and T2D as unfavorable prognostic factors in terms of the presence of the TNBC subtype, tumor metastasis, recurrence, and aggressiveness (G3 and Ki-67 > 20%). This study highlights the importance of prevention in all women, with early screening, and adequate nutritional programs., Competing Interests: We have no conflicts of interest to disclose., (© 2024 The Author(s). Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Introduction: Patient engagement is essential to achieve long-term goals in obesity management. It is crucial to identify patients' perspectives, misperceptions and unmet educational needs on obesity etiology and treatments, to establish a correct therapeutic alliance between healthcare providers and patients., Methods: Objective: This study, promoted by the regional section of the Italian Obesity Society (SIO Lazio), explores attitudes towards obesity, self-awareness, misperceptions of weight loss strategies, experiences of weight stigma and educational needs of patients living with overweight or obesity. Design and subject: We conducted an anonymous survey among patients who accessed an Obesity Management Centers across the Lazio region of Italy for the first time, from October 2023 to April 2024. Approach: The survey consisted of 27 closed-ended questions grouped into 4 sections: (1) sociodemographic factors and self-reported anthropometric measures; (2) self-awareness and attitudes towards obesity and weight loss strategies; (3) experiences of obesity-related stigma; (4) knowledge and perceptions of obesity treatment options., Results: A total of 300 patients (67.9% women, aged 49.1 ± 14.4 years) returned completed surveys. Despite the self-reported BMI 35.3 ± 7.0 kg/m 2 with three out of four (75.3%) of participants having a BMI ≥ 30 kg/m 2 , only 49% correctly identified themselves as affected by obesity. Almost one-third of the patients believed that obesity does not imply a genetic predisposition (31.9%) and that it is always secondary to psychological or behavioral disorders (29.7%). Interestingly, 66.7% of the patients declared themselves as completely responsible for their own condition and 39.4% considered obesity always treatable by means of lifestyle interventions. Stigma and weight discrimination in healthcare settings were reported by a substantial portion of patients (31.9%). A perception of inadequate support from the National Healthcare System emerged in most of the interviews (61.9%). Most patients (72.1%) felt they were not sufficiently informed about anti-obesity medications and a relevant part of their knowledge was derived from healthcare providers (57.7%) and social networks (19.1%). Weight loss medications were considered useful (63.2%) or necessary (18.4%) by the majority of patients, but only 60.1% would accept without any hesitation a pharmacologic treatment. The main reasons for refusal of pharmacological treatments were the belief that lifestyle intervention is a sufficient treatment (46.9%), the fear of adverse effects (28.1%) and feeling defeated (12.5%). Similarly, for most of participants bariatric surgery is useful (73.3%) or necessary (13.6%)., Conclusion: Despite advancements in obesity research, this study underscores the need to improve patient education and public awareness to optimize the management and treatment of obesity. Addressing misconceptions, stigma, and gaps in knowledge are critical steps towards improving patient outcomes and fostering a supportive healthcare environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor MW declared a shared affiliation with the authors SM & DC at the time of review. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Colangeli, Russo, Capristo, Mariani, Tuccinardi, Manco, Scipione, Parrotta, Capoccia and Guglielmi.)

Background : Sex differences characterize the prevalence and attitudes toward weight management. Despite limited evidence suggesting greater weight loss in women with anti-obesity pharmacotherapy, sex-specific analysis remains underexplored. This retrospective study aimed to evaluate the sex-specific response to liraglutide 3.0 mg treatment in people with obesity without type 2 diabetes (T2D). Methods : Data were collected from 47 patients (31 women, 16 men) with age > 18 years; BMI ≥ 30 kg/m 2 ; absence of T2D; and exclusion of prior anti-obesity treatment, comorbidities, or bariatric surgery. Only patients who maintained the liraglutide 3.0 mg dose for at least 6 months were included. Results : Both sexes showed significant reductions in weight and BMI at 3 and 6 months. Men achieved greater weight loss (WL), BMI reduction, %WL, WL > 5%, and >10% than women, and they also showed more significant improvements in metabolic parameters (total and LDL cholesterol, Fibrosis-4 Index FIB-4). No significant sex differences were observed in glucose metabolism or renal function. Conclusions : This study showed a greater therapeutic effect of liraglutide 3.0 mg in men. Given men's higher risk of cardiovascular disease (CVD), and underrepresentation in clinical weight loss programs, these findings may increase male engagement and improve their CVD risk.

Background: Primary care providers (PCPs) play an essential role in obesity care as they represent the first contact for patients seeking weight loss interventions., Objective: This study explored the knowledge, experiences, and perceptions of PCPs in the Lazio Region of Italy in the management of obesity., Design and Subjects: We conducted an anonymous survey delivered from March to July 2022 via the newsletter of Rome Provincial Order of Physicians and Dentists and at the annual meeting of the regional section of the Italian Obesity Society., Approach: The survey consisted of 24 closed-ended questions grouped into 5 sections: sociodemographic and work information; assessment of obesity; management of obesity; connections with regional Centres for Obesity Management; attitudes towards obesity., Key Results: A total of 92 PCPs accessed the survey. Of those, 2.2% were excluded because they did not see any patients with obesity. A total of 68 PCPs (75.6%) had complete questionnaires and were included in this analysis. All participants reported asking their patients about their eating habits, lifestyle, and clinical complications at the first assessment. Body weight and blood pressure were measured by 98.5% of participants and 82% calculate body mass index (BMI), while a small proportion of PCPs analysed body composition and fat distribution. Over 80% prescribed laboratory tests and ECG. Approximately 40% of PCPs did not refer patients for nutritional counselling, and most prescribed a low-calorie diet. Sixty-three percent referred patients to an endocrinologist, 48.5% to a psychotherapist, and a minority to specialists for obesity complications. Twenty-three percent prescribed anti-obesity medications and 46.5% referred patients for bariatric surgery only in severe cases. Ninety-one percent stated that obesity is "a complex and multifactorial disease" and 7.4% considered obesity to be secondary to other conditions., Conclusions: Despite most PCPs adopt a correct approach to manage patients with obesity, many aspects could be improved to ensure optimal and multidisciplinary management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CC declared a shared affiliation with the authors CL, SM, EP to the handling editor at the time of review., (Copyright © 2023 Guglielmi, Capoccia, Russo, Lubrano, Mariani, Poggiogalle, Furia, Alizadeh, Patrizi, Sapienza, Damiani, Tarsitano, Conte and Frontoni.)

Purpose: To study the possible association of CT-derived quantitative epicardial adipose tissue (EAT) and glycemia at the admission, with severe outcomes in patients with COVID-19., Methods: Two hundred and twenty-nine patients consecutively hospitalized for COVID-19 from March 1st to June 30th 2020 were studied. Non contrast chest CT scans, to confirm diagnosis of pneumonia, were performed. EAT volume (cm 3 ) and attenuation (Hounsfield units) were measured using a CT post-processing software. The primary outcome was acute respiratory distress syndrome (ARDS) or in-hospital death., Results: The primary outcome occurred in 56.8% patients. Fasting blood glucose was significantly higher in the group ARDS/death than in the group with better prognosis [114 (98-144) vs. 101 (91-118) mg/dl, p = 0.001]. EAT volume was higher in patients with vs without the primary outcome [103 (69.25; 129.75) vs. 78.95 (50.7; 100.25) cm 3 , p < 0.001] and it was positively correlated with glycemia, PCR, fibrinogen, P/F ratio. In the multivariable logistic regression analysis, age and EAT volume were independently associated with ARDS/death. Glycemia and EAT attenuation would appear to be factors involved in ARDS/death with a trend of statistical significance., Conclusions: Our findings suggest that both blood glucose and EAT, easily measurable and modifiable targets, could be important predisposing factors for severe Covid-19 complications., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: gut microbiota (GM) seems to be involved in the pathophysiology and progression of both metabolic syndrome (MS) and obesity. The aim was to investigate GM's composition in patients with severe obesity, candidates for bariatric/metabolic surgery BMS., Materials and Methods: Multicentre, prospective, cohort study, enrolling 84 patients with BMI 40-55 kg/m 2 , divided bymetabolic status (MS) inhealthy(group A), pre-MS (B), or MS (C)., Results: No differences were foundregarding anthropometric,nutritional parameters, except for vitamin D.As a whole the alpha and beta diversity examinations showed no statistical differences in GM profile. A total of 5/7 phyla with relative frequencies were identified above 0.1% (Actinobacteria,Bacteroidetes,Firmicutes,Proteobacteria,Verrucomicrobia).FusobacteriaandPatescibacteriarepresented the less abundant. There were no significant differences in the top ten genera.Data onBacteroidetes(inversely related to triglycerides and LDL and directly related to HDL levels) and onFirmicutes(opposite trend) relative abundances suggest no differences among the three conditions.No correlation between the relative abundance of themain phylaand plasmatic glucose levels was observed., Conclusions: In a selected cohort of patients with obesity, MS did not affect the preoperative GM's profile. Severe obesity, per se, seems to be an independent condition affecting GM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: To evaluate posturography measurements, and their association with other clinical tests used for cervicogenic dizziness diagnosis, in a cohort of subjects suffering from cervicogenic dizziness, compared with healthy subjects., Materials and Methods: Ninety-three cervicogenic dizziness patients and 98 age- and gender-matched healthy subjects underwent video-Head impulse test, posturography testing, evaluation of cervical spine movements by means of cervical range of motion goniometer and self-report and performance measures, including Dizziness Handicap Inventory, Neck Disability Index, Neck Pain Intensity, Tampa Scale for Kinesiophobia and Hospital Anxiety and Depression Scale., Results: Cervicogenic dizziness patients demonstrated significant increases in classical posturography parameters (i.e., surface and length) and in power spectra values within middle and high-frequency interval depicting balance control alterations especially due to proprioceptive integration changes. Furthermore, decreases in degrees of cervical range of motion and increases of self-report and performance measures - highlighting significant complaints of subjective feeling of dizziness - were found in these patients when compared with healthy subjects. Multiple correlations were found between posturography testing and cervical range of motion and Dizziness Handicap Inventory as well as between different self-report and performance measures in cervicogenic dizziness patients., Conclusions: The implementation of posturography - including power spectra analysis - coupled with appropriate exclusion of other disorders, may represent a useful tool in improving cervicogenic dizziness assessment in terms of cost, time consumption and correlation with other measurements.Implications for rehabilitationUncertainties in diagnostic assessment of cervicogenic dizziness reflect doubts regarding the causes underpinning the symptoms of imbalance, unsteadiness, and disorientation.Posturography measurement is a low-cost, time-sparing technique and its implementations have proven to be useful in detecting significant alterations in body sway during perturbating situations.Implementation of power spectra analysis on posturography testing may represent a useful tool in improving cervicogenic dizziness assessment also in terms of rehabilitative treatment follow-up.

Background: Obesity represents a risk factor for COVID-19 infection. Therefore, in order to reduce COVID-19 related comorbidities in obese population a continuation of obesity treatment is needed. However, bariatric procedures were postponed because of COVID-19 restrictions, delaying treatment for obese patients seeking for surgery. This study aimed to test the feasibility of a telematics pre-operative psychological and nutritional assessment as an alternative tool during COVID-19 outbreak., Methods: Twenty-six patients were contacted. The pre-operative assessment consisted in 3-weekly one-to-one online sessions and a final in-person multidisciplinary session. The protocol feasibility has been evaluated on the following outcome: rejection rate (%), dropout rate (%), compliance and satisfaction's degree., Results: Eighteen participants completed the whole protocol and 10% dropped-out. Seventy-two percent of participants obtained an excess weight loss ≥5%. All participants were satisfied of the telematics assessment., Conclusions: COVID-19 emergency has changed standard hospital procedures and this study could represent a landmark for an online pre-operative assessment method to adopt in case of new restrictions.

Aims: Experimental data suggest that visceral adipose tissue (VAT) dysfunction contributes to non-alcoholic fatty liver disease (NAFLD) development in obesity, however, data on humans are limited. Aims of this study were to investigate the relationship between NAFLD and VAT morphofunctional impairment and to determine whether the extent of VAT remodelling is associated with liver damage and metabolic alterations in obesity., Methods: We analysed data from 40 obese individuals candidate to bariatric surgery in whom paired intraoperative liver and omental biopsies were performed for diagnosing NAFLD and VAT inflammation by immunohistochemistry and mRNA expression studies., Results: Within our study population, NAFLD was significantly associated with greater VAT CD68 + macrophages infiltration (P = .04), fibrosis (P = .04) and impaired microvascular density (P = .03) as well as increased expression of markers of local hypoxia, apoptosis and inflammation (UNC5B, CASP7, HIF1-α, IL-8, MIP2, WISP-1, all P < .01). The degree of VAT inflammation correlated with the severity of hepatic injury (steatosis, inflammation, fibrosis; all P < .01) and impaired gluco-metabolic profile., Conclusions: In obese patients, NAFLD is associated in a dose-dependent manner with signs of VAT remodelling, which reflect more severe clinical metabolic impairment. Our study depicts morphological alterations and novel mediators of VAT dysfunction, adding knowledge for future therapeutic approaches to NAFLD and its metabolic complications., (© 2020 John Wiley & Sons Ltd.)

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes' size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02-1.9; χ 2 test) and with AUROC = 0.89 ( p = 0.002, 95% CI = 0.76-1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and an independent risk factor for cardiovascular mortality. Angiopoietin-like proteins (ANGPTLs) are targets for vitamin D receptor (VDR)-mediated gene transcription and this axis may promote NAFLD. ANGPTL3 is a hepatokine which inhibits lipoprotein lipase and its experimentally induced inactivation reduces hepatosteatosis. Little is known on ANGPTL3 in human NAFLD and no data exist on its relationship with hepatic VDR/VD-related genes. The aim of this research was to investigate hepatic ANGPTLs and VDR/VD-related gene expression in human obesity in relation to NAFLD., Methods: We conducted a cross-sectional investigation on forty obese subjects with/without NAFLD. We evaluated hepatic ANGPTL3, ANGPTL4, ANGPTL8, LPL, VDR, CYP27A1 and CYP2R1 mRNA expression in liver biopsies by RT-PCR; VDR expression was further investigated by immunohistochemistry; circulating ANGPTL3 was measured by Milliplex assay., Results: Compared to non-NAFLD, NAFLD individuals had significantly higher hepatic VDR, ANGPTL3 and LPL expression. ANGPTL3 correlated with steatosis grade, LPL, VDR, CYP27A1 and CYP2R1 expression. Plasma ANGPTL3 concentrations were positively associated with clinical/histological markers of NAFLD/NASH and with hepatic ANGPTL3 expression. Greater hepatic VDR expression was the main determinant of hepatic ANGPTL3 after adjusting for multiple confounders., Conclusions: Hepatic ANGPTL3 expression correlates with greater VDR expression, presence and severity of NAFLD and translates in increased circulating ANGPTL3, likely as a result of its modulation by up-regulated hepatic VDR in NAFLD. This study provides novel insights to potential mechanisms underlying ANGPTLs-mediated ectopic fat accumulation and NAFLD development in obesity., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Purpose: This pilot project describes the development and implementation of two specialised aviation-style checklist designs for a low-frequency high-risk patient population in a cardiac intensive care unit. The effect of the checklist design as well as the implementation strategies on patient outcomes and adherence to best practice guidelines were also explored. The long-term objective was to improve adherence to accepted processes of care by establishing the checklists as standard practice thereby improving patient safety and outcomes., Methods: During this project, 10specialised crisis checklists using two specific aviation-style designs were developed. A quasiexperimental prospective pre-post repeated measure design including surveys along with repetitive simulations were used to evaluate self-confidence and self-efficacy over time as well as the perceived utility, ease of use, fit into workflow and benefits of the checklists use to patients. Performance, patient outcomes and manikin outcomes were also used to evaluate the effectiveness of the crisis checklists on provider behaviours and patient outcomes., Results: Overall self-confidence and self-confidence related to skills and knowledge while not significant demonstrated clinically relevant improvements that were sustained over time. Perceptions of the checklists were positive with consistent utilisation sustained over time. More importantly, use of the checklists demonstrated a reduction in errors both in the simulated and clinical setting., Conclusion: Recommendations from this study consist of key considerations for development and implementation of checklists including: utilisation of stakeholders in the development phase; implementation in real and simulated environments; and ongoing reinforcement and training to sustain use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A number of meta-analyses have demonstrated the effectiveness of bariatric surgery in improving morbid obesity and its associated co-morbidities. The aim of the study was to evaluate at long term a cohort of obese patients with type 2 diabetes (T2DM) submitted to laparoscopic sleeve gastrectomy (LSG) analyzing the incidence of weight regain (WR) and the impact of the WR on T2DM evolution., Methods: Seventy-eight morbid obese patients (54 females) with T2DM, aged 49.6 ± 8.7 years, weight 121.1 ± 24.4 kg, BMI 44.1 ± 7.2 kg/m 2 , underwent primary LSG. The trend over time of T2DM after LSG was analyzed in the different groups, subdivided on the basis of the absence or presence of WR and of its different degrees: no regain (NR), mild regain (MR), and severe regain (SR) groups., Results: In the NR group, 54% show complete remission, 46% persistence, and no case of diabetes relapse; in the MR group, 59% show complete remission, 36% persistence, and 5% relapse; in the SR group, 61% show complete remission, 22% persistence, and 17% relapse. A statistically significant difference concerns the preoperative values of fasting glucose, glycosylated hemoglobin, and duration of diabetes, major in the group with diabetes relapse (respectively, p = 0.002, p = 0.001, and p < 0.0001)., Conclusions: The results of this study showed no significant difference regarding the trend of diabetes remission comparing the "no regain," "mild regain," and "severe regain" groups and confirmed the importance of the duration of the illness and an early intervention towards surgical therapy.

Purpose: In morbid obesity nonalcoholic fatty liver disease (NAFLD) is endemic. Aim of this study is to evaluate the diagnostic accuracy of the most common noninvasive methods for identify NAFLD and fibrosis in a cohort of morbid obese population., Methods: Ninety morbid obese patients undergoing bariatric surgery (BS) and intraoperative liver biopsy were evaluated preoperatively with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and serum biomarkers for steatosis and fibrosis and liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) elastography. All nondiabetic patient (n = 77) underwent OGTT and calculation of Oral Glucose Insulin Sensitivity index (OGIS)., Results: In the entire cohort prevalence of NAFLD was 77%, NASH 24%, moderate/severe steatosis 50%, and significant fibrosis 14%. New cut-offs were evaluated for all steatosis score assessed in this population. In all patients with moderate/severe steatosis HOMA IR was significantly greater than 3.5. ALT, GGT, Triglycerides, HOMA IR, and ARFI increased with fibrosis grade (p 0.03, p 0.008, p 0.04, p 0.05, respectively) and AST to Platelet ratio (APRI) was the only noninvasive fibrosis score significantly increased in significant fibrosis (p 0.04). A combination of 1/OGIS and VAI was able to discriminate NASH from simple steatosis (NAFL) (p 0.02)., Conclusions: In morbid obese subjects, we calculated new cut-offs of the most common steatosis indexes and found that a score based on insulin resistance (1/OGIS) and abdominal obesity (VAI) could represent a way to identify morbid obese subjects at risk of NASH.

Background and Aim: Obese subjects are at high risk of nonalcoholic fatty liver disease (NAFLD) and diabetes (T2D) due to insulin resistance (IR). Since high glucose levels are as toxic as lipids for hepatic metabolism, we hypothesize that altered response to oral glucose tolerance test (OGTT) is associated to more severe NAFLD with significant/advanced liver damage., Methods and Results: We studied 90 subjects with morbid obesity (73F/17M, BMI = 43.2 ± 5,9 kg/m 2 ) undergoing bariatric surgery and intraoperative liver biopsy, and measured HbA1c, HOMA-IR (fasting Glucose x Insulin/22.5), OGTT glucose and insulin profile, and calculated OGIS (muscle insulin sensitivity), hepatic-IR (glucose [AUC 0-30 ] x insulin [AUC 0-30 ]) during OGTT, insulin response as (insulin [dAUC 0-120 ]/glucose [dAUC 0-120 ] or Insulinogenic Index (IGI = (I 30 -I 0 )/(G 30 -G 0 )). Patients were divided in 3 groups according to liver biopsy: A (no-NAFLD, 23%), B (simple steatosis (SS), 53%) and C (NASH, 24%) with similar age, gender and BMI. Diabetes was 0% in no-NAFLD, 13% in SS, 35% in NASH. During OGTT, OGIS decreased from A to C (422 vs 360 vs 338, p < 0.01). Increased insulin concentrations, HbA1c, HOMA-IR and OGIS, not Hep-IR, were strongly associated to hepatic steatosis (p = 0.03, p = 0.0001 and p = 0.01 respectively). Hepatic fibrosis stage was mild as most of the patients had fibrosis grade-1 (69% vs. 8% no fibrosis) and associated to fasting insulin, HbA1c and HOMA-IR. dAUC-I/dAUC-G was similar in the 3 groups, while only AUC-I was strongly associated to steatosis (r = 0.35, p = 0.005), but not to fibrosis., Conclusions: In morbid obesity indexes of IR, and not of insulin response, are markers of histological severity of liver disease., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Biliverdin reductase-A (BVR-A) is a serine/threonine/tyrosine kinase involved in the regulation of insulin signaling. In vitro studies have demonstrated that BVR-A is a substrate of the insulin receptor and regulates IRS1 by avoiding its aberrant activation, and in animal model of obesity the loss of hepatic BVR-A has been associated with glucose/insulin alterations and fatty liver disease. However, no studies exist in humans. Here, we evaluated BVR-A expression levels and activation in peripheral blood mononuclear cells (PBMC) from obese subjects and matched lean controls and we investigated the related molecular alterations of the insulin along with clinical correlates. We showed that BVR-A levels are significantly reduced in obese subjects and associated with a hyper-activation of the IR/IRS1/Akt/GSK-3β/AS160/GLUT4 pathway. Low BVR-A levels also associate with the presence of obesity, metabolic syndrome, NASH and visceral adipose tissue inflammation. These data suggest that the reduction of BVR-A may be responsible for early alterations of the insulin signaling pathway in obesity and in this context may represent a novel molecular target to be investigated for the comprehension of the process of insulin resistance development in obesity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To assess whether vestibulo-ocular reflex (VOR) gain, posturography parameters and related clinical outcomes can improve in OSA patients after 12 months of CPAP treatment, taking into consideration that a certain degree of vestibular dysfunction has been identified in these subjects., Methods: Vestibular, postural, clinical, and polygraphic parameters were assessed in 32 OSA patients before and after beneficial CPAP treatment by means of video head impulse test (vHIT), static posturography (SP), Dizziness Handicap Inventory (DHI), Epworth Sleepiness Scale (ESS), and Apnea-Hypopnea Index (AHI), respectively, and were compared by means of a "within-subject" ANOVA model and Spearman's rank correlation., Results: After the 12-month period of treatment, OSA patients demonstrated a significant reduction in AHI values, in both opened and closed eyes conditions of surface and length as well as in power spectra recorded in low, middle, and high frequency interval. Although a significant improvement was also recorded among DHI and ESS scores, VOR gain increase did not survive to post-hoc corrections. Finally, positive correlations between the differences between pre- and post-treatment AHI, ESS, and PS values were found., Conclusions: The present work highlighted that postural instability and dizziness-related conditions due to OSA may improve after 12 months of CPAP treatment. Although VOR gain did not demonstrate significant improvement, this study might open future perspectives directed to assessing VOR gain changes after longer periods of CPAP treatment.

Introduction: Copeptin is the stable surrogate marker of vasopressin (VP), which is released in response to elevated plasma osmolality or low blood pressure. Elevated plasma copeptin levels are associated with higher risk of insulin resistance-related disorders, such as type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease, and experimental reduction of circulating VP levels is shown to significantly decrease hepatic fat content in obese rats, independently from body adiposity. However, the association between copeptin and non-alcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) in humans has not been explored yet. The aim of this study was to explore the relationship between plasma copeptin and the presence/severity of NAFLD/NASH., Methods: For this study, we recruited 60 obese patients candidate to bariatric surgery for clinical purposes in which intraoperative liver biopsies were performed for diagnosing NAFLD/NASH. Circulating copeptin levels were also assessed in 60 age- and sex-comparable non-obese individuals without NAFLD at liver ultrasonography. Plasma copeptin was measured by sandwich immunoluminometric assay (Thermo Fisher Scientific)., Results: Obese patients with biopsy-proven NAFLD (53%) had significantly higher copeptin levels than both obese individuals without NAFLD and non-obese subjects (ob/NAFLD+ 9.5 ± 4.9; ob/NAFLD- 6.4 ± 2.6; and non-ob/NAFLD- 7.4 ± 5.1 pmol/L; p = 0.004 and p = 0.01 respectively). Plasma copeptin concentration positively correlated with hepatic macro- and micro-vesicular steatosis (r = 0.36, p = 0.026; r = 0.31, p = 0.05), lobular inflammation (r = 0.37, p = 0.024) and significantly increased throughout degrees of NASH severity, as expressed as absence, borderline, and overt NASH at the liver biopsy (r = 0.35, p = 0.01). Greater circulating copeptin predicted the presence of NASH with OR = 1.73 (95% CI = 1.02-2.93) after multivariate adjustment for age, sex, renal function and presence of T2DM and MS components., Conclusions: Increased plasma copeptin is independently associated with the presence and severity of NAFLD and NASH, pointing to a novel mechanism behind human fatty liver disease potentially modifiable by pharmacological treatment and lifestyle intervention.

Objective: ANGPTL4 inhibits lipoprotein lipase in adipose tissue, regulating plasma triglycerides levels. In persons with obesity plasma ANGPTL4 levels have been positively correlated with body fat mass, TG levels and low HDL. A loss-of-function E40K mutation in ANGPTL4 prevents LPL inhibition, resulting in lower TGs and higher HDLc in the general population. Since obesity determines metabolic alterations and consequently is a major risk factor for cardiovascular disease, the aim was to explore if obesity-related metabolic abnormalities are modified by the ANGPTL4 -E40K mutation., Methods: ANGPTL4 -E40K was screened in 1206 Italian participants, of which 863 (71.5%) with obesity. All subjects without diabetes underwent OGTT with calculation of indices of insulin-sensitivity., Results: Participants with obesity carrying the E40K variant had significantly lower TG ( p  = 0.001) and higher HDLc levels ( p  = 0.024). Also in the whole population low TGs and high HDLc were confirmed in E40K carriers. In the obese subpopulation it was observed that almost all E40K carriers were within the lowest quartile of TGs ( p  = 1.1 × 10 -9 ). E40K had no substantial effect of on glucose metabolism. Finally, none of the obese E40K carriers had T2D, and together with the favourable lipid profile, they resemble a metabolically healthy obese (MHO) phenotype, compared to 38% of E40E wild-type obese that had diabetes and/or dyslipidaemia ( p  = 0.0106)., Conclusions: In participants with obesity the ANGPTL4 -E40K variant protects against dyslipidemia. The phenotype of obese E40K carriers is that of a patient with obesity without metabolic alterations, similar to the phenotype described as metabolic healthy obesity.

Background: Recently, significant attention has been paid to the possible activation of an autoimmune response in the presence of obesity. The aim of this study was to evaluate and compare the frequencies of autoantibodies typical of autoimmune diabetes in obese patients with normal glucose tolerance (NGT), obese patients with type 2 diabetes (T2D) and controls. We also evaluated the presence of immunoreactivity to Hashimoto's thyroiditis and autoimmune gastritis., Materials and Methods: Consecutive sera from obese patients, 444 with NGT, 322 with T2D, and 212 controls were analysed by radioimmunoassay or enzyme-linked immunosorbent assay for glutamic acid decarboxylase, protein tyrosine phosphatase islet antigen-2 (IA-2) IC and IA-2 (256-760) , islet beta-cell zinc cation transporter (ZnT8), thyroid peroxidase, and anti-parietal cell autoantibodies., Results: Altogether the presence of organ-specific autoantibodies was significantly more frequent in obese patients with NGT (128/444, 28.5%) and obese with T2D (79/322, 24.5%) than in controls (36/212, 17%; P = 0.002). Thyroid peroxidase immunoreactivity was prevalent in all groups of subjects investigated. The frequencies of diabetes-specific autoantibodies were slightly higher in obese patients with NGT (20/444, 4.5%) than in obese with T2D (12/322, 3.7%) and controls (4/212, 1.9%). The anti IA-2 (256-760) was the most frequent islet autoantibody in obese subjects with NGT (14/20, 70%)., Conclusions: We observed significant evidence of immunoreactivity specific to diabetes, thyroid, and gastric-parietal cells in obese patients with NGT. The relatively higher frequency of the diabetes-related IA-2 (256-760) autoantibodies in obese patients with NGT may suggest that this autoantibody could be associated with obesity the presence of obesity itself., (© 2018 John Wiley & Sons, Ltd.)

Objective: Obesity is one of the major health challenges throughout the world. The association between obesity and diabetes is well established because 90% of patients with type 2 diabetes mellitus (T2DM) show excess body weight. The aim of the study was to evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on morbid obesity and type 2 diabetes (T2DM) in the long-term follow-up., Methods: One hundred ninety-five obese patients, 78 with T2DM, were evaluated before and after LSG up to 10 years, to identify complete diabetes remission (FPG < 100 mg/dl, A1c < 6.0%), partial remission (FPG 100-125 mg/dl, A1c < 6.5%), or relapse., Results: Before surgery, body weight and BMI were 123 ± 21 kg and 44.6 ± 6.8 kg/m 2 respectively; at a mean follow-up of 7 years (range 4-10), body weight was 104.9 ± 18 kg and BMI 37 ± 6 kg/m 2 . Minimum weight was reached after 2 years. T2DM remission was observed in 66, 57, and 52% at short (< 2 years), medium (2-5 years), and long-term (> 5 years) follow-up respectively. Furthermore, 45.2% maintained complete remission for at least 5 years and about 36% showed a persistent but improved diabetes. None of the patients cured from diabetes had a duration disease greater than 8 years and a glycemic control requiring insulin. The prevalence of hypertension and dyslipidemia significantly decreased from 49 to 35% and from 51 to 40% respectively., Conclusions: LSG significantly improves body weight, diabetes, hypertension, and dyslipidemia in long-term follow-up.

Obesity levels, especially in children, have dramatically increased over the last few decades. Recently, several studies highlighted the involvement of gut microbiota in the pathophysiology of obesity. We investigated the composition of gut microbiota in obese adolescents and adults compared to age-matched normal weight (NW) volunteers in order to assemble age- and obesity-related microbiota profiles. The composition of gut microbiota was analyzed by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed, and univariate, multivariate, and correlation analyses performed on bacterial profiles. The prediction of metagenome functional content from 16S rRNA gene surveys was carried out. Ecological analyses revealed a dissimilarity among the subgroups, and resultant microbiota profiles differed between obese adolescents and adults. Using statistical analyses, we assigned, as microbial markers, Faecalibacterium prausnitzii and Actinomyces to the microbiota of obese adolescents, and Parabacteroides , Rikenellaceae, Bacteroides caccae , Barnesiellaceae, and Oscillospira to the microbiota of NW adolescents. The predicted metabolic profiles resulted different in adolescent groups. Particularly, biosynthesis of primary bile acid and steroid acids, metabolism of fructose, mannose, galactose, butanoate, and pentose phosphate and glycolysis/gluconeogenesis were for the majority associated to obese, while biosynthesis and metabolism of glycan, biosynthesis of secondary bile acid, metabolism of steroid hormone and lipoic acid were associated to NW adolescents. Our study revealed unique features of gut microbiota in terms of ecological patterns, microbial composition and metabolism in obese patients. The assignment of novel obesity bacterial markers may open avenues for the development of patient-tailored treatments dependent on age-related microbiota profiles.

Context: Neurotensin (NT), an intestinal peptide released by fat ingestion, promotes lipid absorption; higher circulating NT levels are associated with type 2 diabetes (T2D), obesity, and cardiovascular disease. Whether NT is related to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has not been fully investigated., Objective: To study the relationship between plasma proneurotensin 1 to 117 (pro-NT), a stable fragment of the NT precursor hormone, and the presence/severity of NAFLD/NASH and to unravel correlates of increased pro-NT levels., Design/setting/participants: For this cross-sectional study, 60 obese individuals undergoing bariatric surgery for clinical purposes were recruited. The association between pro-NT and NAFLD was further investigated in 260 consecutive subjects referred to our outpatient clinics for metabolic evaluations, including liver ultrasonography. The study population underwent complete metabolic characterization; in the obese cohort, liver biopsies were performed during surgery., Main Outcome Measures: Plasma pro-NT levels in relation to NAFLD/NASH., Results: Obese subjects with biopsy-proven NAFLD (53%) had significantly higher plasma pro-NT than those without NAFLD (183.6 ± 81.4 vs 86.7 ± 56.8 pmol/L, P < 0.001). Greater pro-NT correlated with NAFLD presence (P < 0.001) and severity (P < 0.001), age, female sex, insulin resistance, and T2D. Higher pro-NT predicted NAFLD with an area under receiver operating characteristic curve of 0.836 [95% confidence interval (CI), 0.73 to 0.94; P < 0.001]. Belonging to the highest pro-NT quartile correlated with increased NAFLD risk (odds ratio, 2.62; 95% CI, 1.08 to 6.40) after adjustment for confounders. The association between higher pro-NT and NAFLD was confirmed in the second cohort independently from confounders., Conclusions: Increased plasma pro-NT levels identify the presence/severity of NAFLD; in dysmetabolic individuals, NT may specifically promote hepatic fat accumulation through mechanisms likely related to increased insulin resistance.

Neurotensin (NT) is a 13-amino acid peptide localized in the neuroendocrine cells of the small intestine, which promotes fat absorption and fatty acids translocation in response to lipid ingestion. NT-knock-out mice fed with a high-fat diet are protected from obesity, fatty liver, and the development of insulin-resistance. In humans, higher plasma levels of pro-NT, which is the stable circulating precursor of NT, predict obesity, type 2 diabetes (T2D), and cardiovascular disease. In obesity, the presence of visceral adipose tissue (VAT) inflammation leads to unfavorable metabolic outcomes and is associated with the development of T2D and non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the relationship between plasma pro-NT levels and the presence of VAT inflammation in biopsies from 40 morbidly obese subjects undergoing bariatric surgery. We demonstrated that higher proNT levels are significantly associated with greater macrophages infiltration, HIF-1&alpha;, WISP-1, and UNC5B expression in VAT (all p < 0.01) due to the diagnosis of T2D and NAFLD. The overall results show that, in obesity, pro-NT is a biomarker of VAT inflammation and insulin-resistance. Additionally, NT may be involved in the development of dysmetabolic conditions likely mediated by increased gut fat absorption and the presence of a proinflammatory milieu in the adipose tissue.

Aim: Vitamin D acts through the binding to the vitamin D receptor (VDR). Several polymorphisms in VDR gene have been studied. Among these, the rs2228570 C>T (FokI) variant has been demonstrated to be functional, leading to a protein with a different size and activity. So far, genetic studies on the association between VDR gene rs2228570 single nucleotide polymorphism (SNP) and type 2 diabetes mellitus (T2DM) showed contradictory results. Thus, we performed an association study in a large cohort of adult Italian subjects with T2DM and in nondiabetic controls., Materials and Methods: For this study, 1713 subjects, 883 T2DM patients and 830 controls, were genotyped for the polymorphism. All participants without a diagnosis of diabetes underwent oral glucose tolerance test (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance (Homeostatic model assessment of insulin resistance, insulin sensitivity index), secretion (homeostatic model assessment for beta-cell, corrected insulin response at 30 minutes) and disposition index were calculated., Results: Genotype distributions and allele frequencies did not show difference between T2DM subjects and controls. We did not find significant differences among the three genotypes regarding gender, age, BMI, waist, hip, waist-to-hip ratio, and blood pressure. There were also no significant differences in lipid parameters, aspartate aminotransferase, and alanine aminotransferase levels. We tested for association with OGTT-derived data and surrogate indices of insulin resistance and secretion. We did not find significant differences among the genotypes in any of above-mentioned parameters. Furthermore, vitamin D levels were measured in a subgroup of subjects. We did not find significant differences among the genotypes., Conclusions: Our study does not provide evidence for the association of the rs2228570 polymorphism with T2DM in a Caucasian population.

Context: Wnt1-inducible signaling pathway protein 1 (WISP1) is a novel adipokine participating in adipose tissue (AT) dysfunction; so far, no data on WISP1 in diabetes are available., Objectives: To evaluate plasma WISP1 in subjects with type 2 diabetes (T2D) and its correlates linked to AT inflammation., Design and Participants: For this cross-sectional study, 97 consecutive dysmetabolic patients were recruited at the diabetes outpatient clinics of Sapienza University in Rome; 71 of them had T2D, with (n = 35) or without (n = 36) obesity, and 26 were obese patients without diabetes. Twenty-one normal-weight nondiabetic individuals were enrolled as a control group. Study participants underwent clinical workup and blood sampling for metabolic/inflammatory characterization; magnetic resonance imaging (MRI) data on subcutaneous AT and visceral AT (VAT) area, hepatic fat content, and VAT homogeneity were available for most diabetic patients., Results: Plasma WISP1 significantly increased throughout classes of obesity and correlated with greater VAT area, interleukin-8 (IL-8), and lower adiponectin levels, without differing between diabetic and nondiabetic participants. Higher IL-8 was the main determinant of increased WISP1. MRI-assessed VAT inhomogeneity was associated with higher WISP1, IL-8 and C-reactive protein levels, independent of obesity; high WISP1 strongly predicted VAT inhomogeneity ( P < 0.001)., Conclusions: WISP1 levels are increased in obese persons and are directly related to adiposity, independent of glycemic status or insulin resistance; moreover, they are strongly associated with increased plasma IL-8 and signal abnormalities of VAT. The overall data add insights to the mechanisms underlying metabolic alterations and may open a scenario for innovative therapeutic approaches for diabetes prevention and care.

Aim: To evaluate whether obesity represents a risk factor for the onset of ovarian cancer., Patients and Methods: One hundred and sixty-three patients with a body mass index (BMI) >30 kg/m 2 (group 1) and 130 women with a BMI of <25 kg/m 2 (group 2) were included in the study., Results: A Risk of Ovarian Malignancy Algorithm (ROMA) index above the cut-off (>13%) was found in 24.5% of group 1 patients, whereas a high ROMA score was identified in 5.3% of group 2 women. During the study, 13 out of 40 group 1 patients with ROMA >13% were deemed eligible for bariatric surgery. After bariatric surgery and decrease of BMI, eight out of these 13 obese women had a ROMA index <13%., Conclusion: The ROMA index may function as a simple test able to screen obese women at risk of developing ovarian cancer., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Perilipin 2 (PLIN2), a member of the family of perilipin lipid droplets coating proteins, is very widely expressed. The Ser251Pro (rs35568725) missense mutation in exon 6 of PLIN2 gene was previously associated with increased lipid accumulation, decreased lipolysis and increased number of small lipid droplets per cell. Furthermore, the Pro251 mutation was associated with decreased plasma triglyceride and very low density lipoprotein concentrations in population studies. The aim of this study was to evaluate the effect of the Ser251Pro mutation of PLIN2 gene in a cohort with a higher predisposition to obesity-associated metabolic alterations, such as insulin resistance, decreased insulin-secretion, hyperglycaemia, and dyslipidaemia., Methods: A large cohort (N = 1692) of Italian obese subjects (mean body mass index = 41 kg/m(2) ) was genotyped for the Ser251Pro mutation. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance and of insulin secretion were also calculated. Clinical and biochemical parameters were collected for all participants., Results: We observed that insulin concentration was significantly reduced at 120 min after the administration of glucose in Pro251 allele carriers, whereas glucose levels were similar in Pro251 allele carriers and non-carriers throughout the OGTT. Furthermore, the CIR120 index of insulin secretion was significantly lower (P < 0.035) and the ISI index of insulin-sensitivity was significantly higher (P < 0.031) in carriers of the Pro251 allele. When we analysed men and women separately to test for gender-specific associations, we observed that in women insulin levels were significantly lower in Pro251 allele carriers compared with wild-type subjects throughout the whole OGTT. In men, we confirmed a significant reduction in insulin concentration only at 120 min after the OGTT. No significant differences between genotype groups regarding triglyceride levels and anyother clinical and metabolic parameters were observed., Conclusion: We observed a strong significant association between the PLIN2 Pro251 mutation and lower insulin secretion associated with an increased insulin sensitivity. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background and Aims: 1α,25-dihydroxyvitamin-D3, the biologically active vitamin D, plays a central role in several metabolic pathways through the binding to the vitamin D receptor (VDR). VDR has been shown to be involved in cardiovascular diseases, cancer, autoimmunity and type 2 diabetes mellitus (T2DM). Several polymorphisms in the VDR gene have been described. Among these, the rs11568820 G-to-A nucleotide substitution was found to be functional, modulating the transcription of the VDR gene. Objective of this study was to perform an association study between rs11568820 polymorphism and T2DM in a cohort of Italian adults with T2DM and in non-diabetic controls. To add further insight into the role of VDR gene we explored whether this association begins early in life in overweight/obese children, or becomes manifest only in adulthood., Methods and Results: As many as 1788 adults and 878 children were genotyped for the rs11568820 polymorphism. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin-resistance and secretion were also calculated. The AA genotype was significantly more frequent in adults with T2DM compared to controls (7.5% vs. 4.6%, P = 0.037), and conferred a higher risk of T2DM (ORHom = 1.69C.I. = [1.13-2.53], P = 0.011). In the adult cohort, rs11568820 was also associated with reduced indices of β-cell insulin secretion. In children, the AA genotype was associated with 2 h high-normal glucose, a marker of cardio-metabolic risk., Conclusions: Our study demonstrates for the first time that VDR gene AA carriers have higher risk of T2DM and impaired insulin secretion. In children, the association between AA homozygous and high-normal 2h glucose suggests that mild alterations associated with this genotype may appear early in life., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aims: Apelin is a peptide produced and secreted by white adipose tissue. It is synthesized as preproapelin, a protein containing 77 aminoacids which is then cleaved to shorter active fragments. As an adipokine, apelin plays a role in the regulation of many biological functions, including body energy homeostasis and glucose metabolism, water balance, and immunity. We have recently demonstrated that subjects with type 2 diabetes (T2D) have significantly higher serum apelin levels compared with controls, and that these levels associate with fasting glucose, basal disposition index, age, and diagnosis of T2D. The first aim of this study was to search for sequence variants in the apelin gene (APLN), located on chromosome Xq25-q26.1 that may associate with serum levels of apelin. The second aim was to analyze the possible association between diabetes and diabetes-related traits and APLN variants., Methods: We designed a two-step genetic association study. Step one consisted of an initial screen of 100 individuals selected from the extremes of the apelin distribution levels wherein we sequenced the APLN gene to identify common variants. In step two, the rs181301686 with a minor allele frequency >0.2 was genotyped in 917 individuals to explore its association with T2D and diabetes-related traits., Results: Five sequence variations were found across the APLN gene. To test for association with apelin levels, the rs181301686 and rs2281069 single-nucleotide polymorphisms were genotyped in 256 subjects for whom serum apelin levels were available. No significant differences were observed in apelin levels between genotypes. Association analysis in 917 individuals did not show significant differences between APLN genotypes and diabetes and diabetes-related traits., Conclusions: Resequencing of the apelin gene in subjects stratified by low or high apelin levels identified five APLN variants in an European population. No association was found between the most frequent variant, diabetes, and metabolic parameters.

Background and Aims: The rate of mortality in diabetic patients, especially of cardiovascular origin, is about twice as much that of nondiabetic individuals. Thus, the pathogenic factors shaping the risk of mortality in such patients must be unraveled in order to target intensive prevention and treatment strategies. The "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes" is aimed at identifying new molecular promoters of mortality and major vascular events in patients with type 2 diabetes mellitus (T2DM)., Methods/design: The "SUMMER study in diabetes" is an observational, prospective, and collaborative study conducted on at least 5000 consecutive patients with T2DM, recruited from several diabetes clinics of Central-Southern Italy and followed up for a minimum of 5 years. The primary outcome is all-cause mortality; the secondary outcomes are cardiovascular mortality, acute myocardial infarction, stroke, and dialysis. A biobank will be created for genomic, transcriptomic, and metabolomic analysis, in order to unravel new molecular predictors of mortality and vascular morbidity., Discussion: The "SUMMER study in diabetes" is aimed at identifying new molecular promoters of mortality and major vascular events in patients with T2DM. These novel pathogenic factors will most likely be instrumental in unraveling new pathways underlying such dramatic events. In addition, they will also be used as additional markers to increase the performance of the already existing risk-scoring models for predicting the above-mentioned outcomes in T2DM, as well as for setting up new preventive and treatment strategies, possibly tailored to specific pathogenic backgrounds., Trial Registration: ClinicalTrials.gov, NCT02311244; URL https://clinicaltrials.gov/ct2/show/NCT02311244?term=SUMMER&rank=5., (Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Psychiatric disorders are common in obese patients and they are often considered contraindications for bariatric surgery. In this patients Axis I profile has been widely investigated, while only few studies on Axis II profile are reported. Aim of the study was to examine the prevalence of Axis II psychopathology, to describe the typical body image and to evaluate the prevalence of childhood abuse in bariatric surgery candidates., Materials and Methods: A total of 102 consecutive obese patients (77 females) were evaluated by the Structured Clinical Interview for DSM IV which assessed Axis I Disorders. After the exclusion of Axis I Disorders, 50 patients (36 females, BMI: 44.68 ± 9.48 Kg/m2, age: 44.5 ± 11.7 years) were enrolled. All 50 patients received a psychiatric assessment including the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II); the Body Uneasiness Test, part a (BUT-A), which assesses body image disorders; the Childhood Trauma Questionnaire (CTQ) as a screening test of childhood maltreatment histories., Results: Nineteen patients (38%) were affected by Axis II disorders. Cluster C disorders, including avoidant, dependent and obsessive-compulsive personality disorders, represented the most common diagnosis (24%). Moreover, 34 patients (68%) showed body image disorders (BID), with a GSI score ≥1.2 and 24 (48%) referred an abuse during childhood. Patients with Axis II disorder or a body image uneasiness or a history of maltreatment during childhood, showed higher BMI in adulthood., Conclusions: Psychiatric comorbidities in obese patients were not only represented by depression or anxiety (Axis I disorders), but also by personality disorders (Axis II), body image disorders and childhood abuse. The identification of these conditions could improve outcomes of bariatric surgery and represent an indication for a most important psychiatric support before, during and after surgery.

Background: We evaluated the effectiveness of a sequential diet regimen termed the obese preoperative diet (OPOD) in morbidly obese patients with and without type 2 diabetes mellitus (T2DM) scheduled for laparoscopic bariatric surgery., Methods: Fifty patients (body mass index 53.5 ± 8.4 kg/m(2)) scheduled for bariatric surgery, including 14 with T2DM, were prospectively enrolled and followed the OPOD regimen: a very low-calorie ketogenic diet for 10 days, followed by a very low-calorie diet for 10 days, and then a low-calorie diet for 10 days. Patients were evaluated at baseline (T0) and after 10 days (T1), 20 days (T2), and 30 days (T3)., Results: Body weight, body mass index, waist circumference, and neck circumference were significantly lower at T1, T2, and T3 than at T0 in the 48 patients who completed the OPOD. Two patients discontinued the OPOD after 4-7 days. In patients with T2DM, fasting plasma glucose levels decreased significantly, enabling reduction of diabetic medications. Plasma and urine ketone levels increased at T1 but were all <1 mmol/L, and hunger decreased during the diet period., Conclusions: OPOD, including 10 days of a VLCKD, was safe and effective in morbidly obese patients, and it seems to be promising in morbidly obese patients with and without T2DM scheduled for laparoscopic bariatric surgery.

The study was carried out on type 2 diabetic obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Patients underwent regular glycemic controls throughout 3 years and all patients were defined cured from diabetes according to conventional criteria defined as normalization of fasting glucose levels and glycated hemoglobin in absence of antidiabetic therapy. After 3 years of follow-up, Continuous Glucose Monitoring (CGM) was performed in each patient to better clarify the remission of diabetes. In this study, we found that the diabetes resolution after LSG occurred in 40% of patients; in the other 60%, even if they showed a normal fasting glycemia and A1c, patients spent a lot of time in hyperglycemia. During the oral glucose tolerance test (OGTT), we found that 2 h postload glucose determinations revealed overt diabetes only in a small group of patients and might be insufficient to exclude the diagnosis of diabetes in the other patients who spent a lot of time in hyperglycemia, even if they showed a normal glycemia (<140 mg/dL) at 120 minutes OGTT. These interesting data could help clinicians to better individualize patients in which diabetes is not resolved and who could need more attention in order to prevent chronic complications of diabetes.

Background: Metabolic syndrome (MS) and hypovitaminosis D represent two of the most diffuse condition worldwide, reaching pandemic proportions in industrialized countries, and are both strongly associated with obesity. This study set out to evaluate the presence of an independent association between hypovitaminosis D and MS in an adult population of obese subjects with/without MS., Methods: We recruited 107 consecutive obese subjects, 61 with MS (age(mean±SD) 45.3±13.3 years, BMI(mean±SD): 43.1±8.3 kg/m(2)) and 46 without MS (age: 41.8±11.5, p = n.s., BMI:41.6±6.5 kg/m(2), p = n.s.) comparable for sex, BMI, waist circumference and body fat mass, evaluated by bioimpedentiometry. 25(OH) vitamin D3 levels were measured by colorimetric method. Insulin resistance was estimated by fasting blood insulin, HOMA-IR and ISI., Results: Serum 25(OH)D3 levels were significantly lower in MS obese patients than in obese subjects without MS (median(range) 13.5(3.3-32) vs 17.4(5.1-37.4), p<0.007). Low 25(OH)D3 levels correlated with glycaemia (p<0.007), phosphate (p<0.03), PTH (p<0.003) and the MS (p<0.001). Multivariate model confirmed that low 25(OH)D3 levels were associated with the diagnosis of MS in obese patients independently from gender, age, serum PTH and body fat mass. After stratifying the study population according to 25(OH)D3 concentrations, patients in the lowest quartile showed a markedly increased prevalence of MS compared to those in the highest quartile (OR = 4.1, CI 1.2-13.7, p = 0.02)., Conclusions: A powerful association exists between hypovitaminosis D and MS in obese patients independently from body fat mass and its clinical correlates. This indicates that the association between low 25(OH) D3 levels and MS is not merely induced by vitamin D deposition in fat tissue and reinforces the hypothesis that hypovitaminosis D represent a crucial independent determinant of MS.

Background: The aim of this study was to evaluate the long-term effects of laparoscopic sleeve gastrectomy (LSG) on type 2 diabetes mellitus (T2DM) and other related co-morbidities in severely obese patients., Methods: From May 2003 to July 2008, 33 morbidly obese diabetic patients (20 with body mass index [BMI]>50 kg/m(2)) underwent LSG. A total of 23 females and 10 males participated, with a mean age of 49.3±8 years, mean preoperative BMI of 52.1±8.5 kg/m(2), mean fasting plasma glucose (FPG) of 143.2±47.9 mg/dL, mean glycosylated hemoglobin (HbA1c) of 7.3%±1.4%, and a mean T2DM duration of 7 years. All patients had a 36-month follow-up, and 13 had a 60-month follow-up., Results: Twenty-nine patients (87.8%) discontinued antidiabetic medications 3 months after LSG, (mean BMI of 42.8±7.8 kg/m(2); FPG of 104.5±22.1 mg/dL; HbA1c of 5.3%±.4%). At 36 months, 22 of 26 LSG patients (84.6%) had normal FPG and HbA1c values without antidiabetic therapy. At the 60-month follow-up, 10 of 13 patients (76.9%) had normal FPG and HbA1c values without antidiabetic therapy. The Framingham risk score decreased significantly from 9.7% preoperatively to 4.7% postoperatively. No new diabetic retinopathy occurred during the whole period of observation., Conclusions: This study confirms the efficacy of LSG in the treatment of T2DM and indicates that, at both 36- and 60-month follow-ups, LSG can provide a significant percentage of treated patients with a prolonged remission of T2DM, with diminished cardiac risk factors and no development of diabetic retinopathy. These results compare favorably with those reported after standard medical therapy., (Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the effect of sleeve gastrectomy vs medical therapy on type 2 diabetes mellitus and other obesity-related comorbidities (obstructive sleep apnea syndrome, hypertension, and dyslipidemia) in prospectively enrolled and matched obese patients with type 2 diabetes., Design: A prospective cohort study. Morbidly obese patients with type 2 diabetes who either underwent sleeve gastrectomy or conventional therapy were followed up and assessed for their diabetic state and other comorbidities every 3 months for 18 months., Setting: Centre for the Surgical-Medical Treatment of Morbid Obesity, Policlinico “Umberto I,” University of Rome “Sapienza,” Italy., Patients: A total of 30 morbidly obese patients with type 2 diabetes who underwent sleeve gastrectomy (group A) and a total of 30 morbidly obese patients with type 2 diabetes who underwent conventional therapy (group B)., Results: In group A, the preoperative mean (SD) body mass index, fasting plasma glucose level, and hemoglobin A1c level were 41.3 (6.0), 166.6 (68.1) mg/dL, and 7.9% (2.1%), respectively, and, at 18 months, these values were 28.3 (5.4), 96.2 (29.4) mg/dL, and 6.0% (1.5%), respectively. For 80% of patients, diabetes was resolved. With regard to other comorbidities, the prevalence of obstructive sleep apnea syndrome dropped from 50% to 10%, and patients reduced significantly their use of medication for hypertension and dyslipidemia. In group B, the preoperative mean (SD) body mass index, fasting plasma glucose level, and hemoglobin A1c level were 39.0 (5.5), 183.7 (63.5) mg/dL, and 8.1% (1.7%), respectively, and, at 18 months, these values were 39.8 (5.0), 150 (48) mg/dL, and 7.1% (1.3%), respectively. All patients remained diabetic and continued or increased their level of hypoglycemic therapy. With regard to other comorbidities, we observed an increase in the use of medication for hypertension and dyslipidemia, and the prevalence of obstructive sleep apnea syndrome did not change., Conclusions: This study confirms the efficacy of sleeve gastrectomy in the treatment of morbidly obese type 2 diabetic patients when compared with conventional medical treatment.

Background: Apelin is an adipokine that plays a role in the regulation of glucose homeostasis and in obesity. The relationship between apelin serum concentration and dysmetabolic conditions such as type 2 diabetes (T2D) is still controversial. Aims of our study are: 1) determine the circulating levels of apelin in a large cohort of Italian subjects with T2D, T1D and in non-diabetic controls; 2) identify putative metabolic determinants of modified apelin concentrations, in order to search possible mechanism of apelin control; 3) investigate changes in apelin levels in response to sharp modifications of glucose/insulin metabolism in T2D obese subjects before and 3 days after bariatric surgery., Methods: We recruited 369 subjects, 119 with T2D, 113 with T1D and 137 non-diabetic controls. All subjects underwent a complete clinical examination, including anthropometric and laboratory measurements. Serum apelin levels were determined by EIA (immunoenzyme assay)., Results: Patients with T2D had significantly higher serum apelin levels compared to controls (1.23 ± 1.1 ng/mL vs 0.91 ± 0.7 ng/mL, P<0.001) and to T1D subjects (0.73 ± 0.39 ng/mL, P<0.001). Controls and T1D subjects did not differ significantly in apelin levels. Apelin concentrations were directly associated with fasting blood glucose (FBG), body mass index (BMI), basal Disposition Index (DI-0), age, and diagnosis of T2D at bivariate correlation analysis. Multiple regression analysis confirmed that diagnosis of T2D, basal DI-0 and FBG were all determinants of serum apelin levels independently from age and BMI. Bariatric surgery performed in a subgroup of obese diabetic subjects (n = 12) resulted in a significant reduction of apelin concentrations compared to baseline levels (P = 0.01)., Conclusions: Our study demonstrates that T2D, but not T1D, is associated with increased serum apelin levels compared to non-diabetic subjects. This association is dependent on impaired glucose homeostasis, and disappears after bariatric surgery, providing further evidence regarding the relationship between apelin and the regulation of glucose metabolism.

Background: Type 2 diabetes mellitus (T2DM) and obesity are diseases of epidemic proportions. Long-term realistic weight loss by nonsurgical methods has a variable effect on glycemic control, and only a proportion of patients with T2DM have a worthwhile response. Laparoscopic sleeve gastrectomy (LSG) has been proposed as an advantageous bariatric procedure for patients with a lower body mass index (BMI). Our objective was to compare the effects of LSG and medical therapy on patients with T2DM and a BMI of <35 kg/m(2)., Methods: A total of 18 nonmorbidly obese patients with T2DM, diagnosed according to the American Diabetes Association guidelines, were consecutively enrolled. Of these patients, 9 underwent LSG (group A) and 9 underwent conventional medical therapy (group B). The 2 groups were matched for BMI, glycated hemoglobin (HbA1c) and C-peptide levels, pretrial therapy type, and number of patients with a T2DM duration of >10 years., Results: In group A, T2DM resolution was achieved in 8 (88.8%) of the 9 patients (T2DM duration 5.2 yr). Hypertension was controlled in all 8 of 9 patients. Dyslipidemia was corrected. In 1 patient, obstructive sleep apnea syndrome improved. In group B, all 9 patients continued to have T2DM and required hypertensive and hypolipemic therapies throughout the observation period. At baseline, 3 patients were affected by obstructive sleep apnea syndrome and remained affected 1 year later., Conclusion: The results of the present study have confirmed the efficacy of LSG in the treatment of nonmorbidly obese T2DM patients, with a remission rate of 88.8% without undesirable excessive weight loss. The results in this group of patients add to those obtained by us in patients with a BMI >35 kg/m(2)., (Copyright © 2012 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Obesity is recognized as a major health problem worldwide. Genetic factors play a major role in obesity, and genomewide association studies have provided evidence that several common variants within the fat mass- and obesity-associated (FTO) gene are significantly associated with obesity. Very limited data is available on FTO in the Italian population. Aims of our study are to investigate: (1) the association of FTO gene SNPs rs9939609 and rs9930506 with body mass index (BMI) and obesity-related parameters in a large cohort (n = 752) of Italian obese subjects; (2) the association between the two FTO SNPs and age of onset of obesity. Our results demonstrate a strong association between FTO SNPs rs9939609 (P < 0.043) and rs9930506 (P < 0.029) with BMI in the Italian population. FTO rs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI + 1.4 kg/m² per G allele). We also observed that the association with BMI of the two FTO variants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability in FTO on BMI in a large Italian population.

Background. Laparoscopic gastric sleeve (LGS) has been recently introduced as a stand-alone, restrictive bariatric surgery. Theoretically, LGS attenuates micronutrients deficiencies and associated complications that were typically observed following malabsorptive procedures. The aim of this study was to assess some micronutrients and mineral deficiencies in patients undergoing LGS. Methods. In the period between July 2008 and April 2010, 138 obese patients (110 females and 28 males) with mean BMI 44.4 kg/m(2) ± 6.5, mean age 43.9 ± 10.9 years were enrolled and underwent LGS. Patients were followed up with routine laboratory tests and anthropometric measurements and assessed for nutritional status, as regards vitamin B12, folic acid, iron, hemoglobin, calcium, and vitamin D, every three months throughout 12 months. Results. 12 months after sleeve, patients did not show iron deficiency and/or anemia; plasma calcium levels were in the normal range without supplementation from the sixth month after the operation. Vitamin B12 and folic acid were adequately supplemented for all the follow-up period. Vitamin D was in suboptimal levels, despite daily multivitamin supplementation. Conclusion. In this study, we showed that LGS is an effective surgery for the management of morbid obesity. An adequate supplementation is important to avoid micronutrients deficiencies and greater weight loss does not require higher dosage of multivitamins.

Background: The aim of this study was to evaluate the possible role of sleeve gastrectomy (SG) per se in the reversibility of diabetes., Methods: Insulin secretion and peripheral insulin sensitivity using the intravenous glucose tolerance test (IVGTT) were assessed in 18 obese type 2 diabetic patients and in 10 nondiabetic obese patients before and 3 days after SG, before any food intake and any weight change occurrence. At the same time, ghrelin, GLP-1, and PYY levels were determined., Results: In diabetic patients who had the disease less than 10.5 years, the first phase of insulin secretion promptly improved after SG. The early insulin area under the curve (AUC) significantly increased at the postoperative IVGTT, indicating an increased glucose-induced insulin secretion. The second phase of insulin secretion (late AUC) significantly decreased after SG in all groups, indicating an improved insulin peripheral sensitivity. In all groups, pre- and postoperatively, intravenous glucose stimulation determined a decrease in ghrelin values and an increase in GLP-1 and PYY values. However, in the group of patients with disease duration >10.5 years, the differences were not significant except for the late insulin AUC. Postoperative basal and intravenous glucose-stimulated ghrelin levels were lower than preoperative levels in all groups of patients. Basal and intravenous stimulated GLP-1 and PYY postoperative values were higher than preoperative levels in all groups., Conclusions: Restoration of the first phase of insulin secretion and improved insulin sensitivity in diabetic obese patients immediately after SG, before any food passage through the gastrointestinal tract and before any weight loss, seem to be related to ghrelin, GLP-1, and PYY hormonal changes of possible gastric origin and was neither meal- nor weight-change-related. Duration of the disease up to 10.5 years seems to be a major cut off in the pathophysiological changes induced by SG. A "gastric" hypothesis may be put forward to explain the antidiabetes effect of SG.

Background: Several studies have demonstrated a high rate of type 2 diabetes mellitus (T2DM) resolution after sleeve gastrectomy. Different prognostic factors have been hypothesized for T2DM remission after bariatric surgery. Our objectives were to analyze the role of T2DM duration as an independent prognostic factor for remission., Methods: From January 2008 to September 2010, 56 obese patients with T2DM underwent sleeve gastrectomy. Group A consisted of 16 patients who had lived with T2DM for >10 years (12 women and 4 men, mean body mass index 42.7 kg/m2). Group B included 40 obese patients who had lived with T2DM for <10 years (29 women and 11 men, mean body mass index 44.9 kg/m2)., Results: In group A, 43.7% were treated with oral hypoglycemics, 6.3% with insulin, and 50% with oral hypoglycemics and insulin. In group B, 87.5% were treated with oral hypoglycemics, 5% with dietary therapy, and 7.5% with insulin. The preoperative average glycemia, glycosylated hemoglobin, and C-peptide value was 206.2 mg/dL, 9.5%, and 2.8 μg/L in group A and 134 mg/dL, 7.1%, and 4.5 μg/L in group B, respectively (P < .05 for all). The T2DM remission rate in all 56 patients was 80.3%. However, in group B, the resolution rate was 100%, but in group A, the resolution rate was 31%. Patients without complete remission were more sensitive to lower doses of antidiabetic drugs., Conclusion: Sleeve gastrectomy is effective in the treatment of obese patients with T2DM. The duration of T2DM seems to be of paramount importance as a prognostic factor, with 10 years representing a cutoff between a 100% rate of remission and significantly lower rates of remission., (Copyright © 2011 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Aims: Among the electrocardiographic alterations used for stratifying the cardiovascular risk of life threatening arrhythmias (LFA) and sudden death (SD) there is the increment of the corrected QT(QTc). This increment is usually observable in obese patients (OP). Therefore, a study has been planned to investigate the possibility to predict QTc values in OP simply by detecting the best fitting regression method that represents the relationship between QTc and Body Mass Index (BMI)., Materials and Methods: The study has been carried on 144 individuals classified as a function of their BMI in normoponderal subjects (NPS, No. 24; F/M=15/9; BMI=21.8± 1.7 kg/m(2)), Class I OP (No. 24; F/M=17/7; BMI=32.5± 1.1 kg/m(2)); Class II OP (No. 24; F/M=17/7; BMI=37.7± 1.5 kg/m(2)). Class IIIa (No. 24, F/M=15/9; BMI=44.4± 27 kg/m(2)), Class IIIb (No. 24; F/M=14/10; BMI 54.3± 2.7 kg/m(2)); Class IIIc (No. 24; F/M=14/10; BMI=63.3± 4.5 kg/m(2)). Both linear and non-linear fitting modes have been tested., Results: While the BMI progressively increases in classified OP, the QTc shows an intergroup difference that is not only not constant but also declining in Class IIIc obesity. The optimal regressive model was found to be the following fourth order degree polynomial: QTc=317,15+(7,47xBMI)+(-0,28*BMI(2))+(0,005xBMI(3))+ (-0,00003xBMI(4))., Conclusion: By entering the BMI of a given OP into the above-cited formula, the QTc can be easily predicted and compared to that of NPS. Importantly, to have the possibility for a pre-electrocardiographic estimation of QTc allows all the medical and paramedical personnel, involved in the multidisciplinary treatment of obesity, to immediately establish the cardiovascular risk in the OP under observation.

Background: This study aimed to compare the efficacy of laparoscopic sleeve gastrectomy (SG) with that of laparoscopic gastric bypass (GBP) and laparoscopic adjustable gastric banding (AGB) for glucose homeostasis in morbidly obese subjects with type 2 diabetes mellitus (T2DM) at a 3-year follow-up assessment and to elucidate the role of weight loss in the T2DM resolution after SG., Methods: For this study, 60 morbidly obese T2DM patients (44 females and 16 males) who underwent AGB (24 patients), GBP (16 patients), or SG (20 patients) between 1996 and 2008 were retrospectively analyzed. Age, sex, body mass index (BMI), estimated weight loss (EWL), fasting glycemia, HbA1c, euglycemic hyperinsulinemic clamp, discontinuation of diabetes treatment, and time until interruption of therapy were evaluated., Results: In the study, 54 patients received oral hypoglycemic agents for at least 12 months before surgery, and 6 patients received insulin. The mean follow-up period was 36 months. The resolution rate was 60.8% for the AGB patients, 81.2% for the GBP patients, and 80.9% for the SG patients. The postoperative time until interruption of therapy was 12.6 months for the AGB patients, 3.2 months for the GBP patients, and 3.3 months for the SG patients. The hyperinsulinemic euglycemic clamp test was performed 12 months after surgery for the cured patients. Insulin resistance was restored to normal values in all the patients. The greatest improvement from preoperative values occurred in the SG group. For the not-cured GBP and SG patients, an improvement of 120 mg/dl in fasting plasma glucose was observed 3 months after the surgery, suggesting an enhancement in insulin sensitivity, which determines better medical control. The resolution rate remained constant at the 36-month follow-up evaluation in both the GBP and SG groups., Conclusions: All three bariatric procedures are effective in treating diabetes, with a 3-year follow-up evaluation showing an effect that lasts. The AGB procedure was the least effective. The antidiabetic effect was similarly precocious after GBP and SG compared with AGB. This difference may indicate that a hormonal mechanism may be involved, independent of weight loss.