Investigating the potential non-authorized use of two different formulations of liraglutide in Europe: A real-world drug utilization study.

AIM: To assess the in-market use of Saxenda (liraglutide 3.0 mg) and Victoza (liraglutide 1.2 mg/1.8 mg) according to approved indications and posology. MATERIALS AND METHODS: This retrospective, non-interventional study was conducted at 41 sites from December 2016 to May 2019. Via medical record review, physicians at each site identified patients who had been prescribed Saxenda (Italy) or Victoza (Italy/Germany) within the 24 months following launch in each country. Pseudonymized data were abstracted on patient and site characteristics, indication for the prescription, posology and duration of usage. Adherence to the approved indications and posology, and to the Saxenda stopping rule, were assessed. No formal statistical analysis was performed. RESULTS: A total of 440 patients were prescreened and 225 (51.1%) were enrolled (Saxenda: N = 75, all in Italy; Victoza: N = 75 in Italy and N = 75 in Germany). In all, 96% (72/75) of Saxenda prescriptions, and 98.7% (148/150) of Victoza, were in accordance with the approved indications. Among the 40 patients treated with Saxenda for 16 weeks or longer, only two (5.0%) were confirmed as non-adherent to the stopping rule. Adherence could not be assessed in 23 (57.5%) patients because of missing body weight measurements. CONCLUSIONS: This retrospective, real-world post-authorization safety study provides reassurance that Saxenda and Victoza are primarily used according to the approved European label, thus their real-world utilization did not raise safety concerns.

Outpatient healthcare costs associated with overweight and obesity in Italy.

BACKGROUND: To evaluate outpatient healthcare expenditure associated with different levels of BMI and glucose metabolism alterations. METHODS: The study is based on a representative national sample of adults, with data obtained from electronic clinical records of 900 Italian general practitioners. Data relative to the year 2018 were analyzed. The study population was classified according to BMI (normal weight, overweight, and obesity classes 1, 2, and 3) and glucose metabolism status (normoglycemia - NGT; impaired fasting glucose - IFG; diabetes mellitus - DM). Outpatient health expenditures include diagnostic tests, specialist visits, and drugs. RESULTS: Data relative to 991,917 adults were analyzed. Annual per capita expenditure rose from 252.2 Euro among individuals with normal weight to 752.9 Euro among those with class 3 obesity. The presence of obesity determined an excess cost, particularly among younger individuals. Within each BMI class, the presence of IFG or DM2 identified subgroups of individuals with substantially higher healthcare expenditures. CONCLUSIONS: Outpatient healthcare costs markedly increased with increasing BMI in all age categories, particularly among individuals below 65. Addressing the double burden of excess weight and hyperglycemia represents a significant challenge and a healthcare priority.

Obesity management: at the forefront against disease stigma and therapeutic inertia.

Obesity is a complex chronic relapsing disease, resulting from the interaction between multiple environmental, genetic and epigenetic causes, and supported by changes in the neuroendocrine mechanisms regulating energy balance and body weight. Adipose tissue dysfunction contributes to obesity-related complications. However, the prevalent narrative about the causes and mechanisms of obesity remains a much more simplistic one, based on the false assumption that individuals can fully control their body weight through appropriate behavioural choices. According to this narrative, obesity is simply reversible "persuading" the patient to follow healthier and more virtuous individual behaviours (moral judgement). This persistent narrative forms the deep root of the stigmatisation of people with obesity at the individual level and creates a clear discrepancy on how obesity prevention and cure are designed in comparison with the case of other non-communicable chronic diseases (clinical stigma). The promotion of systemic preventive measures against obesity is not supported at a political and social level by the persistence of a narrative of obesity as the simple consequence of individual failures and lack of willpower. The simplistic narrative of obesity as a self-imposed condition with an easy way-out ("eat less and move more") creates a clear discrepancy on how obesity is managed by health care systems in comparison with other NCDs. The over-estimation of the efficacy of therapeutic intervention solely based on patients education and lifestyle modification is responsible of therapeutic inertia in health care professionals and in clinical guidelines, limiting or delaying the adoption of more effective therapeutic strategies, like anti-obesity medications and bariatric surgery. In conclusion, the persistence of a narrative describing obesity as a self-induced easily reversible condition has profound consequences on how obesity prevention and management are build, including the design and implementation of obesity management guidelines and a tendency to therapeutic inertia.Level of evidence: No level of evidence.

Bariatric surgery for metabolic unhealthy obesity (MUO) during the COVID era: short-term results of a high-volume center.

PURPOSE: During the coronavirus disease 19 (COVID-19) outbreak, most public hospitals worldwide have been forced to postpone a major part of bariatric surgery (BS) operations with unfavorable consequences for weight and obesity complications. The aim of this study was to evaluate the effectiveness and safety of laparoscopic BS on subjects with metabolically unhealthy obesity (MUO) during COVID-19 pandemic in a high-volume Italian center. METHODS: Between March 2020 and January 2021, all patients with MUO submitted to laparoscopic BS (sleeve gastrectomy [SG], one anastomosis gastric bypass [OAGB] and Roux-en-Y gastric bypass [RYGB]) were enrolled according to the ATP III Guidelines, with a minimum follow-up of 3 months. RESULTS: In the study period, 210 patients with MUO underwent laparoscopic BS (77 RYGB, 85 SG and 48 OAGB) in our obesity referral center. Postoperative major complications occurred in 4 patients (1.9%) with zero mortality. At 9-month follow-up, a total weight loss (TWL) of 28.2 ± 18.4, 26.1 ± 23.1 and 24.5 ± 11.3% (p = 0.042) was observed in RYGB, OAGB and SG groups, respectively. The rate of comorbidity resolution was very similar for all type of surgeries (p = 0.871). Only two cases of postoperative SARS-CoV-2 infection were registered (0.9%) and both cases resolved with medical therapy and observation. CONCLUSION: Among the patients studied, all surgical techniques were safe and effective for MUO during the COVID era. This group of patients is at high risk for general and SARS-CoV-2-related mortality and therefore should be prioritized for BS. LEVEL OF EVIDENCE: Level III, single-center retrospective cohort study.

Updating obesity management strategies: an audit of Italian specialists.

Obesity negatively affects physical and psychological health and increases health care costs. Although there is increasing interest in early diagnosis and timely intervention, there are several principles of care included in the current guidelines for clinical management of obesity that can potentially be updated and improved to address the "clinical inertia" and, consequently, to optimize the management of adult obesity. Using an online Delphi-based process, an Italian board of experts involved in the management of obesity discussed the usefulness of a pro-active approach to the care of patients with obesity, providing a consensus document with practical indications to identify risk factors for morbidity and death and raise awareness throughout the treatment continuum, including the early stages of the disease. In clinical practice, it seems inappropriate to delay an intervention that could avoid progression to a more severe level of obesity and/or prevent the onset of obesity-related comorbidities.Level of evidence Level V, report of expert committee.

Susceptibility and Severity of Viral Infections in Obesity: Lessons from Influenza to COVID-19. Does Leptin Play a Role?

The recent pandemic Sars-CoV2 infection and studies on previous influenza epidemic have drawn attention to the association between the obesity and infectious diseases susceptibility and worse outcome. Metabolic complications, nutritional aspects, physical inactivity, and a chronic unbalance in the hormonal and adipocytokine microenvironment are major determinants in the severity of viral infections in obesity. By these pleiotropic mechanisms obesity impairs immune surveillance and the higher leptin concentrations produced by adipose tissue and that characterize obesity substantially contribute to such immune response dysregulation. Indeed, leptin not only controls energy balance and body weight, but also plays a regulatory role in the interplay between energy metabolism and immune system. Since leptin receptor is expressed throughout the immune system, leptin may exert effects on cells of both innate and adaptive immune system. Chronic inflammatory states due to metabolic (i.e., obesity) as well as infectious diseases increase leptin concentrations and consequently lead to leptin resistance further fueling inflammation. Multiple factors, including inflammation and ER stress, contribute to leptin resistance. Thus, if leptin is recognized as one of the adipokines responsible for the low grade inflammation found in obesity, on the other hand, impairments of leptin signaling due to leptin resistance appear to blunt the immunologic effects of leptin and possibly contribute to impaired vaccine-induced immune responses. However, many aspects concerning leptin interactions with inflammation and immune system as well as the therapeutical approaches to overcome leptin resistance and reduced vaccine effectiveness in obesity remain a challenge for future research.

Is type 2 diabetes an adiposity-based metabolic disease? From the origin of insulin resistance to the concept of dysfunctional adipose tissue.

In the last decades of the past century, a remarkable amount of research efforts, money and hopes was generated to unveil the basis of insulin resistance that was believed to be the primary etiological factor in the development of type 2 diabetes. From the Reaven's insulin resistance syndrome to the DeFronzo's triumvirate (skeletal muscle, liver and beta-cell) and to Kahn's discovery (among many others) of insulin receptor downregulation and autophosphorylation, an enthusiastic age of metabolic in vivo and in vitro research took place, making the promise of a resolutory ending. However, from many published data (those of insulin receptoropathies and lipodystrophies, the genome-wide association studies results, the data on reversibility of type 2 diabetes after bariatric surgery or very-low-calorie diets, and many others) it appears that insulin resistance is not a primary defect but it develops secondarily to increased fat mass. In particular, it develops from a mismatch between the surplus caloric intake and the storage capacity of adipose tissue. On this basis, we propose to change the today's definition of type 2 diabetes in adiposity-based diabetes.Level of Evidence as a narrative review a vast array of studies have been included in the analysis, ranging from properly designed randomized controlled trials to case studies; however, the overall conclusion may be regarded as level IV.

Misperceptions and barriers to obesity management: Italian data from the ACTION-IO study.

PURPOSE: Despite the increasing prevalence of obesity in Italy, it remains largely underdiagnosed and undertreated. We aimed to identify the perceptions, attitudes, behaviours and barriers to effective obesity care among people with obesity (PwO) and healthcare professionals (HCPs) in Italy. METHODS: The ACTION-IO study was an online cross-sectional survey conducted in 11 countries from June to October 2018. Findings from the Italian cohort are reported here. RESULTS: The survey was completed by 1501 PwO and 302 HCPs in Italy. Most PwO (84%) and HCPs (77%) acknowledged the large impact of obesity on overall health. However, fewer PwO (62%) than HCPs (91%) perceived obesity as a chronic disease. Most PwO (84%) assumed full responsibility for their weight loss. A median of 3 (mean 6) years elapsed between when PwO started struggling with obesity and when they first discussed their weight with an HCP. Many PwO expressed that they liked (80%) or would like (74%) their HCPs to initiate weight management conversations, and only 3% were offended by such a conversation. For 77% of HCPs, perceiving their patients as unmotivated or disinterested in losing weight prevented them from initiating these conversations. Short appointment times were also considered a limiting factor for 40% of HCPs. CONCLUSIONS: Most PwO took complete responsibility for their own weight loss and waited considerable time before seeking help from an HCP. There is a need for improved education of both PwO and HCPs and for a more positive attitude from HCPs towards initiating weight discussions with PwO. Trial registration ClinicalTrials.gov: Awareness, Care & Treatment in Obesity Management - an International Observation (ACTION-IO). ClinicalTrials.gov: NCT03584191 LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Gaps to bridge: Misalignment between perception, reality and actions in obesity.

AIMS: Despite increased recognition as a chronic disease, obesity remains greatly underdiagnosed and undertreated. We aimed to identify international perceptions, attitudes, behaviours and barriers to effective obesity care in people with obesity (PwO) and healthcare professionals (HCPs). MATERIALS AND METHODS: An online survey was conducted in 11 countries. Participants were adults with obesity and HCPs who were primarily concerned with direct patient care. RESULTS: A total of 14 502 PwO and 2785 HCPs completed the survey. Most PwO (68%) and HCPs (88%) agreed that obesity is a disease. However, 81% of PwO assumed complete responsibility for their own weight loss and only 44% of HCPs agreed that genetics were a barrier. There was a median of three (mean, six) years between the time PwO began struggling with excess weight or obesity and when they first discussed their weight with an HCP. Many PwO were concerned about the impact of excess weight on health (46%) and were motivated to lose weight (48%). Most PwO (68%) would like their HCP to initiate a conversation about weight and only 3% were offended by such a conversation. Among HCPs, belief that patients have little interest in or motivation for weight management may constitute a barrier for weight management conversations. When discussed, HCPs typically recommended lifestyle changes; however, more referrals and follow-up appointments are required. CONCLUSIONS: Our international dataset reveals a need to increase understanding of obesity and improve education concerning its physiological basis and clinical management. Realization that PwO are motivated to lose weight offers an opportunity for HCPs to initiate earlier weight management conversations.

Type 2 diabetes: Does pancreatic fat really matter?

With the increasing prevalence of obesity, the interest of research in nonalcoholic fatty pancreas disease (NAFPD) has grown. Even though the pancreas appears more susceptible to lipid accumulation compared with the liver, NAFPD has been less investigated due to the limits in detecting techniques. Several definitions and synonyms for NAFPD are used by authors and can be misleading. This, together with differences in methodology and ethnicity, make the integration and comparison of studies on this topic challenging. NAFPD could be used as an early indicator of ectopic fat deposition, which is recognized as a key factor of obesity cardio-metabolic complications. However, evidence that NAFPD has a pathogenetic role in type 2 diabetes is also emerging. This article reviews the current state of knowledge on the clinical and pathophysiologic relevance of NAFPD in ß-cell function and insulin resistance.

Obesity phenotypes: depot-differences in adipose tissue and their clinical implications.

Obesity, defined as excess fat mass, increases risks for multiple chronic diseases, such as type 2 diabetes, cardiovascular disease, and several types of cancer. Beyond adiposity per se, the pattern of fat distribution, android or truncal as compared to gynoid or peripheral, has a profound influence on systemic metabolism and hence risk for obesity complications. Not only factors as genetics, environment, gender, and age account for the apparent compartmentalization of white adipose tissue (WAT) in the body. Indeed, the heterogeneity among different anatomical depots also appears to stem from their intrinsic diversity, including cellular developmental origin, proliferative capacity, glucose and lipid metabolism, insulin sensitivity, cytokine pattern, thermogenic ability, and vascularization. Under the obese condition, these depot-specific differences translate into specific WAT distribution patterns, giving rise to different cardiometabolic consequences. This review summarizes the clinical and mechanistic evidence for the depot-specific differences and the phenotypic characteristics of different WAT depots that link their depot-specific biology to obesity-specific complications.

GLP-1 receptor independent pathways: emerging beneficial effects of GLP-1 breakdown products.

The glucagon-like peptide-1 (GLP-1) axis has emerged as a major therapeutic target for the treatment of type 2 diabetes and, recently, of obesity. The insulinotropic activity of the native incretin hormone GLP-1(7-36)amide, which is mainly exerted through a unique G protein-coupled receptor (GLP-1R), is terminated via enzymatic cleavage by dipeptidyl peptidase-IV that generates a C-terminal GLP-1 metabolite GLP-1(9-36)amide, the major circulating form in plasma. GLP-1(28-36)amide and GLP-1(32-36)amide are further cleavage products derived from GLP-1(7-36)amide and GLP-1(9-36)amide by the action of a neutral endopeptidase known as neprilysin. Until recently, GLP-1-derived metabolites were generally considered metabolically inactive. However, emerging evidence indicates that GLP-1 byproducts have insulinomimetic activities that may contribute to the pleiotropic effects of GLP-1 independently of the canonical GLP-1R. The recent studies reporting the beneficial effects of the administration of these metabolites in vivo and in vitro are the focus of this review. Collectively, these results suggest that GLP-1 metabolites inhibit hepatic glucose production, exert antioxidant cardio- and neuroprotective actions, reduce oxidative stress in vasculature and have both anti-apoptotic and proliferative effects in pancreatic ß-cells, putatively by the modulation of mitochondrial functions. These findings have implication in energy homeostasis, obesity and its associated metabolic and cardiovascular complications as well as incretin-based therapies for the treatment of diabetes and obesity.

Massive obesity and hyperphagia in posterior bilateral periventricular heterotopias: case report.

BACKGROUND: Bilateral posterior periventricular nodular heterotopia PNH is a complex malformation of cortical development with imaging features distinguishing it from classic bilateral PNH associated with filamin (FLNA) mutations. It distinctively consists of variably sized nodules of neurons along the trigones and temporal or occipital horns of the lateral ventricles and spectrum of developmental disorders of the mid-/hindbrain. This association suggests that pPNH is part of a more diffuse process of posterior or infrasylvian brain developmental abnormalities other than just a disorder of neuronal migration. CASE PRESENTATION: This report describes the first case of an Italian young girl featuring pPNH and severe hyperphagic obesity. At the time of our first examination at age 3 years of age she was severely obese (body mass index, BMI 45.9 Kg/m(2)) and food-seeking behavior in the free-living situation was reported by the relatives. She showed normal linear growth and cognition, but mildly dysmorphic facial traits including deeply-set eyes, prominent zygomatic bones, downturned mouth corners and low-set ears. Over the years, the patient progressively developed further massive weight gain (at age 9 years, her BMI was 60.4 Kg/m(2)) and hyperphagia was confirmed by an ad libitum test meal. During follow-up, she presented limitations in walking capacity and in physical functioning due to the disabling obesity. On the basis of distinctive neuro-radiological findings pPNH was diagnosed, in absence of history of seizures. CONCLUSION: The present case may contribute to the expansion of the phenotypic expressions of this distinctive complex malformation.

The role of epsilon PKC in acute and chronic diseases: Possible pharmacological implications of its modulators.

Epsilon Protein kinase C (εPCK) is a particular kinase that, when activated, is able to protect against different stress injuries and therefore has been proposed to be a potential molecular target against acute and chronic diseases. Particular attention has been focused on εPCK for its involvement in the protective mechanism of Ischemic Preconditioning (IPC), a powerful endogenous mechanism characterized by subthreshold ischemic insults able to protect organs against ischemic injury. Therefore, in the past decades several εPCK modulators have been tested with the object to emulate εPCK mediate protection. Among these the most promising, so far, has been the ΨεRACK peptide, a homologous of RACK receptor for εPKC, that when administrated can mimic its effect in the cells. However, results from studies on εPCK indicate controversial role of this kinase in different organs and diseases, such as myocardial infarct, stroke, diabetes and cancer. Therefore, in this review we provide a discussion on the function of εPCK in acute and chronic diseases and how the different activators and inhibitors have been used to modulate its activity. A better understanding of its function is still needed to definitively target εPCK as novel therapeutic strategy.

Liver protein profiles in insulin receptor-knockout mice reveal novel molecules involved in the diabetes pathophysiology.

Liver has a principal role in glucose regulation and lipids homeostasis. It is under a complex control by substrates such as hormones, nutrients, and neuronal impulses. Insulin promotes glycogen synthesis, lipogenesis, and lipoprotein synthesis and inhibits gluconeogenesis, glycogenolysis, and VLDL secretion by modifying the expression and enzymatic activity of specific molecules. To understand the pathophysiological mechanisms leading to metabolic liver disease, we analyzed liver protein patterns expressed in a mouse model of diabetes by proteomic approaches. We used insulin receptor-knockout (IR(-/-)) and heterozygous (IR(+/-)) mice as a murine model of liver metabolic dysfunction associated with diabetic ketoacidosis and insulin resistance. We evaluated liver fatty acid levels by microscopic examination and protein expression profiles by orthogonal experimental strategies using protein 2-DE MALDI-TOF/TOF and peptic nLC-MS/MS shotgun profiling. Identified proteins were then loaded into Ingenuity Pathways Analysis to find possible molecular networks. Twenty-eight proteins identified by 2-DE analysis and 24 identified by nLC-MS/MS shotgun were differentially expressed among the three genotypes. Bioinformatic analysis revealed a central role of high-mobility group box 1/2 and huntigtin never reported before in association with metabolic and related liver disease. A different modulation of these proteins in both blood and hepatic tissue further suggests their role in these processes. These results provide new insight into pathophysiology of insulin resistance and hepatic steatosis and could be useful in identifying novel biomarkers to predict risk for diabetes and its complications.

Morning meal more efficient for fat loss in a 3-month lifestyle intervention.

OBJECTIVE: To evaluate the effects of 2 low-calorie diets but with different distributions of calories throughout the day on weight loss and other major obesity-related metabolic parameters. METHODS: We randomly assigned 42 nonsmoking homemakers (age = 46.3 ± 2.3 years, body mass index [BMI] = 35.7 ± 0.8 kg/m(2), mean ± SD) in 2 groups of 21 subjects (G1 and G2). The participants underwent a 3 month individualized Mediterranean-style diet (55% carbohydrate, 30% fat, 15% protein and fiber > 30 g), calorie (600 kcal daily deficit compared to the total energy expenditure measured by a metabolic Holter). Diets consisted of the same food and complied with cardiovascular disease prevention guidelines but differed in the distribution of calories throughout the day (G1: 70% breakfast, morning snack, lunch and 30% afternoon snack and dinner; G2: 55 breakfast, morning snack, lunch and 45% afternoon snack and dinner). Dual-energy X-ray absorptiometry was used for pre- and postintervention body composition assessment. RESULTS: Thirty-six subjects completed the study (G1 = 18, G2 = 18). Both groups had significant improvements in body composition and metabolic parameters but G1 had enhanced results for weight loss (G1: -8.2 ± 3.0 kg; G2: -6.5 ± 3.4 kg; p = 0.028), waist circumference reduction (G1: -7 ± 0.6 cm; G2: -5 ± 0.3 cm; p = 0.033), and fat mass loss (G1: -6.8 ± 2.1 kg, G2: -4.5 ± 2.9 kg, p = 0.031; mean ± SD). Improvements were detected in both groups for blood pressure and blood and lipid parameters. G1 subjects showed a greater improvement in insulin sensitivity measured by homeostasis model assessment-estimated insulin resistance (G1: -1.37 ± 0.27, G2: -0.74 ± 0.12, p = 0.017). CONCLUSIONS: These data suggest that a low-calorie Mediterranean diet with a higher amount of calories in the first part of the day could establish a greater reduction in fat mass and improved insulin sensitivity than a typical daily diet.

From simplicity towards complexity: the Italian multidimensional approach to obesity.

Obesity is the result of a complex interplay among several factors leading to medical, functional and psychosocial consequences that markedly reduce life expectancy and impair quality of life. Is obesity itself a disease? Is obesity a brain disease? Who should treat obesity? This paper is a narrative review aimed to describe and to argue the prevalent position of some major Italian scientific and academic institutions dealing with obesity. According to the recent statements and recommendations published by the Italian Society for Obesity (SIO) and the Italian Society for the Study of Eating Disorders (SISDCA), the management of obese patients should include five main levels of care: (1) primary care, (2) outpatient treatment, (3) intensive outpatient treatment, (4) residential rehabilitative treatment, and (5) hospitalization. Ideally, patients suffering from obesity need a multidimensional evaluation intended to design an individualized treatment plan applying different procedures and therapeutic strategies (diet, physical activity and functional rehabilitation, educational therapy, cognitive-behavior therapy, drug therapy, and bariatric surgery). This thorough approach should address not only weight loss but also quality of weight loss, medical and psychiatric comorbidity, psychosocial problems, and physical disability. Such management of obesity requires an effective multiprofessional team, while health services have to overcome a number of administrative and organizational barriers that do not account for diseases requiring resources and professionals from different areas of medicine. Integrating several competences in a team-based approach demands specific education, skills and expertise. As for other diseases, the principles of complexity theory may offer a model useful to implement both teamwork and care delivery for patients with obesity.

Laparoscopic Sleeve Gastrectomy with Staple-Line Oversewing in a Patient with Factor XI Deficiency: A Case Report.

BACKGROUND Bariatric surgery (BS) has a lower percentage of complications than other abdominal surgeries. Hemorrhage in one of the most common complications and can be life-threatening. Hereditary factor XI (FXI) deficiency is a coagulation disorder that can result in excessive bleeding requiring intervention to restore hemostasis. Risks over benefits in patients with morbid obesity with BS indication, as well as those with FXI deficiency, should be carefully evaluated. This article reports the case of an obese woman with FXI deficiency -undergoing SG. CASE REPORT A 49-year-old woman with a BMI of 51 kg/m² was diagnosed as having severe FXI deficiency during preoperative exams prior to bariatric surgery. Virus-inactivated homo-group plasma 10 ml/kg infusion was administrated 1 h before surgery, during the entire procedure, and continuing until postoperative day (POD) 4. A very low-calorie ketogenic diet (VLCKD) was proposed to the patient 4 weeks before surgery. Laparoscopic sleeve gastrectomy was performed with staple-line reinforcement by oversewing the seromuscular layer using continuous suture. Subcutaneous enoxaparin 4000 U.I. was administered from POD 1 until POD 25 to prevent any thromboembolic event. The patient was discharged on POD 5 in good clinical condition. CONCLUSIONS Risks of bleeding andor thromboembolic events before or after BS are increased in patient with FXI deficiency. Bariatric surgery in these patients is safe in experienced BS centers, and the risks associated with the obesity seem to exceed those of the coagulopathy and surgery. Careful preoperative counseling, extensive hematological checks, and meticulous surgery are essential to reduce BS risks. Sleeve gastrectomy oversewing the stapler line seems a reasonable choice.

The interplay between excess weight and hyper-glycemia on NCDs in Italy: results from a cross-sectional study.

PURPOSE: To evaluate the prevalence of chronic comorbidities according to BMI classes and assess the interplay between excess body weight and blood glucose abnormalities in increasing the risk of major chronic diseases. METHODS: The study is based on data from the Health Search/IQVIA Health LPD Longitudinal Patient Database, an Italian general practice registry, with data obtained from electronic clinical records of 800 general practitioners throughout Italy. Data relative to the year 2018 were analyzed. The study population was classified according to BMI (normal weight, overweight, and obesity classes 1, 2 and 3) and glucose metabolism status (normoglycemia-NGT; impaired fasting glucose-IFG; diabetes mellitus-DM). Comorbidities were identified through ICD-9 CM codes. RESULTS: Data relative to 991,917 adults were analyzed. The prevalence of overweight was 39.4%, while the prevalence of obesity was 11.1% (class 1: 7.9%, class 2: 2.3%, class 3: 0.9%). In the whole population, the prevalence of DM and IFG was 8.9% and 4.2%, respectively. Both overweight and obesity were associated with an increasing prevalence of glucose metabolism alterations and a large array of different chronic conditions, including cardio-cerebrovascular diseases, heart failure, chronic kidney disease, osteoarticular diseases, depression, sleep apnea, and neoplasms of the gastrointestinal tract. Within each BMI class, the presence of IFG, and to a greater extent DM, identified subgroups of individuals with a marked increase in the risk of concomitant chronic conditions. CONCLUSION: Addressing the double burden of excess weight and hyperglycemia represents an important challenge and a healthcare priority.

Lifetime costs of overweight and obesity in Italy.

We use longitudinal electronic clinical data on a large representative sample of the Italian population to estimate the lifetime profile costs of different BMI classes - normal weight, overweight, and obese (I, II, and III) - in a primary care setting. Our research reveals that obese patients generate the highest cost differential throughout their lives compared to normal weight patients. Moreover, we show that overweight individuals spend less than those with normal weight, primarily due to reduced expenditures beginning in early middle age. Our estimates could serve as a vital benchmark for policymakers looking to prioritize public interventions that address the obesity pandemic while considering the increasing obesity rates projected by the OECD until 2030.