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Background: The body mass index (BMI) is an imperfect clinical measure of obesity that should be used in conjunction with other valid measures of weight-related risk. We studied whether there is a superior measure of obesity-related comorbidities., Methods: Records of bariatric clinic patients who had an abdominal computed tomography (CT) within 1 year of visit were reviewed. The presence of obesity-related comorbidities was determined at the time of the scan. BMI and ponderal index (PI) were calculated, and CT scans were reviewed to determine the visceral cross-sectional area (VCSA), subcutaneous fat cross-sectional area (SFCSA), and liver volume (LV). Data were analyzed using the Kruskal-Wallis test and Mann-Whitney U test., Results: A higher number of comorbidities were found to be associated with a larger BMI (P = .011), VCSA (P = .014), SFCSA (P = .007), and LV (P = .014), but not a larger PI (P = .11). Of the 16 comorbidities assessed, VCSA and LV were associated with more than BMI and SFCSA. However, each measure could be associated with different comorbidities. A higher BMI was associated with increased insulin use (P = .034), hypertension (P = .007), and history of obstructive sleep apnea (P = .015), none of which were associated with PI. BMI and PI were the only measures associated with a history of deep vein thrombosis/pulmonary embolism (both P < .01). Only SFCSA was found to be associated with gastroesophageal reflux disease (P = .029). VCSA (P = .038) and LV (P = .001) were associated with nonalcoholic fatty liver disease., Conclusion: No measure could account for all obesity-related comorbidities, implying the need for targeted measurements. However, PI was the least effective measure., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

This study investigates the effects of bariatric surgery on non-alcoholic fatty liver disease (NAFLD) by examining the interplay between gut microbiota, epigenetics, and metabolic health. A cohort of 22 patients undergoing sleeve gastrectomy (SG) was analyzed for changes in gut microbial composition and DNA methylation profiles before and six months after surgery. Correlations between gut microbial abundance and clinical markers at baseline revealed that certain genera were associated with worse metabolic health and liver markers. Following SG, significant improvements were observed in the clinical, anthropometric, and biochemical parameters of the NAFLD patients. Although alpha-diversity indices (i.e., Chao1, Simpson, Shannon) did not show significant changes, beta-diversity analysis revealed a slight shift in microbial composition (PERMANOVA, p = 0.036). Differential abundance analysis identified significant changes in specific bacterial taxa, including an increase in beneficial Lactobacillus species such as Lactobacillus crispatus and Lactobacillus iners and a decrease in harmful taxa like Erysipelotrichia. Additionally, DNA methylation analysis revealed 609 significant differentially methylated CpG sites between the baseline values and six months post-surgery, with notable enrichment in genes related to the autophagy pathway, such as IRS4 and ATG4B. The results highlight the individualized responses to bariatric surgery and underscore the potential for personalized treatment strategies. In conclusion, integrating gut microbiota and epigenetic factors into NAFLD management could enhance treatment outcomes, suggesting that future research should explore microbiome-targeted therapies and long-term follow-ups on liver health post-surgery. [ABSTRACT FROM AUTHOR]

In the past 3 decades, metabolic-associated fatty liver disease (MAFLD) has emerged as a widespread liver condition, with its global prevalence on the rise. It ranks as a leading contributor to hepatocellular carcinoma (HCC) and necessitates liver transplantation. Under the multiple parallel hits model, the pathogenesis of MAFLD stems from various liver stressors, notably nutrient overload and sedentary lifestyles. While medical management for MAFLD is well-established, encompassing non-pharmaceutical and pharmaceutical interventions, determining the most effective pharmaceutical therapy has remained elusive. This review discusses diabetic medications for MAFLD treatment, emphasizing recent studies and emerging drugs while reviewing other nondiabetic agents. Emerging evidence suggests that combination therapies hold promise for resolving MAFLD and metabolic steatohepatitis (MASH) while managing side effects. Ongoing trials play a pivotal role in elucidating the effects of mono, dual, and triple receptor agonists in individuals with MASH. With the rising burden of MAFLD/MASH and its severe consequences, the need for effective treatments is more pressing than ever. This review provides a comprehensive overview of the current landscape of pharmaceutical interventions for MAFLD and MASH, shedding light on the potential of newer drugs especially diabetic medications and the importance of ongoing research in this field. [ABSTRACT FROM AUTHOR]

Introduction: Bariatric surgery is the mainstay of treatment of obesity, with a proven, long-lasting effect on body weight reduction and remission of co-morbidities. Sleep disorders, including insomnia, and deteriorated sleep quality and duration are associated with obesity, and a reduction in body weight can be associated with a reduction in prevalence of sleep disorders. The purpose of this study was to assess the influence of laparoscopic sleeve gastrectomy (LSG) on the prevalence and intensity of different sleep disturbances. Methods: This observational prospective study included 80 patients qualified for bariatric surgery who filled in a questionnaire with a set of structured questions about different sleep disturbances, such as difficulties in falling asleep, night awakenings, early morning awakenings, snoring, and nightmares, as well as eating at night and daytime dysfunction, supplemented with Athens Insomnia Scale (AIS), before and 6 months after bariatric surgery. Results: There was a statistically significant reduction in incidence of night awakenings, with 40.00% of participants reporting night awakenings before surgery and, respectively, 25.00% after surgery. A significant reduction was also observed in the rate of patients who reported snoring, with 60.00% before the surgery and 38.75% after the surgery (p < 0.05). There was a correlation present between estimated weight loss % (EWL%) and reduction in snoring (p < 0.05). The mean total AIS score before surgery was 7.21 and 5.99 after surgery, and the change was statistically significant (p < 0.05). A total AIS score of 8 or more, the cutoff score for insomnia diagnosis according to the Polish validation of the Athens Insomnia Scale, was present in 44.16% of cases before surgery and in 38.00% after surgery (p = 0.52). There was a significant difference in the incidence of awakening during the night score before and after surgery (p < 0.05; CI 0.022–0.341), sleep quality (p < 0.05; CI 0.0105–0.4311), well-being during the day (p < 0.05; CI 0.0273–0.4143), and sleepiness during the day (p < 0.05; CI 0.101–0.444). Conclusions: LSG is observed to have a positive effect on selected sleep disturbances and insomnia remission in patients with obesity, measured by a significant reduction in Athens Insomnia Scale scores in follow-up 6 months after surgery. Additionally, patients after bariatric surgery reported less night awakenings and there was a lower rate of snoring. Therefore, LSG can be considered an effective therapeutic tool for insomnia in patients with obesity. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between GGT/HDL-C ratio and resolution of MetS in adults after sleeve gastrectomy (SG). Methods: We conducted a retrospective cohort study using secondary data from a Peruvian bariatric center. The study population consisted of adults aged 18 and above who underwent laparoscopic SG and were diagnosed with MetS prior to the surgery. The main outcome measured was MetS resolution 6 months post-surgery and the exposure variable was the GGT/HDL-C ratio. Results: We analyzed 137 patients with a mean age of 38.9 ± 10.9 years; 64.2% were females. The median GGT/HDL-C ratio was 1.1 [0.7 – 1.5], and 83.9% of patients experienced resolution of MetS. Furthermore, both the middle tertile of GGT/HDL-C (aRR: 1.28; 95% CI: 1.04 - 1.58; p =.019) and the lowest tertile (aRR: 1.27; 95% CI: 1.01 - 1.60; p =.038) showed a significant association with the resolution of MetS. Conclusion: Eight out of 10 patients undergoing SG experience resolution of MetS within 6 months after surgery. Patients in the middle and lower tertiles of the GGT/HDL-C were more likely to achieve this outcome. Therefore, the GGT/HDL-C ratio should be considered a valuable and efficient biomarker for preoperative assessment of bariatric surgery candidates. [ABSTRACT FROM AUTHOR]

(1) Background: Modulators of the Neuropeptide Y (NPY) system are involved in energy metabolism, but the effect of NPY receptor antagonists on metabolic-dysfunction-associated steatotic liver disease (MASLD), a common obesity-related comorbidity, are largely unknown. In this study, we report on the effects of antagonists of the NPY-2 receptor (Y2R) in comparison with empagliflozin and semaglutide, substances that are known to be beneficial in MASLD. (2) Methods: Diet-induced obese (DIO) male Wistar rats were randomized into the following treatment groups: empagliflozin, semaglutide ± PYY3-36, the Y2R antagonists JNJ 31020028 and a food-restricted group, as well as a control group. After a treatment period of 8 weeks, livers were weighed and histologically evaluated. QrtPCR was performed to investigate liver inflammation and de novo lipogenesis (in liver and adipose tissue). Serum samples were analysed for metabolic parameters. (3) Results: Semaglutide + PYY3-36 led to significant weight loss, reduced liver steatosis (p = 0.05), and decreased inflammation, insulin resistance, and leptin levels. JNJ-31020028 prevented steatosis (p = 0.03) without significant weight loss. Hepatic downregulation of de novo lipogenesis-regulating genes (SREBP1 and MLXIPL) was observed in JNJ-31020028-treated rats (p ≤ 0.0001). Food restriction also resulted in significantly reduced weight, steatosis, and hepatic de novo lipogenesis. (4) Conclusions: Body weight reduction (e.g., by food restriction or drugs like semaglutide ± PYY3-36) is effective in improving liver steatosis in DIO rats. Remarkably, the body-weight-neutral Y2R antagonists may be effective in preventing liver steatosis through a reduction in de novo lipogenesis, making this drug class a candidate for the treatment of (early) MASLD. [ABSTRACT FROM AUTHOR]

Paraoxonase-1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). Reduced serum PON1 activity is found in diseases marked by oxidative stress and inflammation, but its role in obesity remains unclear. This study investigated PON1 activities and concentrations in morbidly obese individuals and explored the impacts of the genetic polymorphism PON1 rs662 and non-alcoholic fatty liver disease on enzymatic properties. We recruited 1349 morbidly obese patients undergoing bariatric surgery and 823 non-obese volunteers. PON1-related variables, including arylesterase, paraoxonase, and lactonase activities and PON1 concentrations, were examined. Our results showed that morbidly obese individuals exhibited higher PON1 concentrations but lower enzymatic activities than non-obese individuals. We observed inverse associations of arylesterase and paraoxonase activities with waist circumference (rho = −0.24, p < 0.001, and rho = −0.30, p < 0.001, respectively) and body mass index (rho = −0.15, p = 0.001, and rho = −0.23, p < 0.001), as well as direct associations of arylesterase, paraoxonase, and lactonase activities with HDL cholesterol (rho = 0.11, p = 0.005, rho = 0.20, p < 0.001, and rho = 0.20, p < 0.001). No significant differences were observed regarding metabolic syndrome, type 2 diabetes mellitus, hypertension, dyslipidemia, rs662 polymorphism allele frequencies, or the diagnosis of non-alcoholic steatohepatitis. Nevertheless, correlations were found between certain PON1-related variables, steatosis, and ballooning. In conclusion, changes in PON1-related variables in morbidly obese patients are dependent on the disease itself and HDL levels. The relationships between these variables and specific liver histological changes raise intriguing questions for consideration in future studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-alcoholic fatty liver disease affects up to a quarter of the adult population in many developed and developing countries. This disease has become the fastest-growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of hepatocarcinoma varies between patients with cirrhosis and noncirrhotic patients. In this review, HCC associated with non-alcoholic fatty liver disease will be described, considering its epidemiology, risk factors, and management, including preventive strategies and therapeutic approaches. Non-alcoholic fatty liver disease (NAFLD) affects up to a quarter of the adult population in many developed and developing countries. This spectrum of liver disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. The incidence of NASH is projected to increase by up to 56% over the next 10 years. There is growing epidemiological evidence that NAFLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of HCC varies between patients with NASH cirrhosis and patients with noncirrhotic NAFLD. In this review, NAFLD/NASH-associated HCC will be described, including its epidemiology, risk factors promoting hepatocarcinogenesis, and management of HCC in patients with obesity and associated metabolic comorbidities, including preventive strategies and therapeutic approaches to address this growing problem. [ABSTRACT FROM AUTHOR]

Obesity,and metabolic dysfunction-associated fatty liver disease (MAFLD) have reached epidemic proportions globally. Obesity and MAFLD frequently coexist and act synergistically to increase the risk of adverse clinical outcomes (both hepatic and extrahepatic). Type 2 diabetes mellitus (T2DM) is the most important risk factor for rapid progression of steatohepatitis and advanced fibrosis. Conversely, the later stages of MAFLD are associated with an increased risk of T2DM incident. According to the proposed criteria, MAFLD is diagnosed in patients with liver steatosis and in at least one in three: overweight or obese, T2DM, or signs of metabolic dysregulation if they are of normal weight. However, the clinical classification and correlation between obesity and MAFLD is more complex than expected. In addition, treatment for obesity and MAFLD are associated with a reduced risk of T2DM, suggesting that liver-based treatments could reduce the risk of developing T2DM. This review describes the clinical classification of obesity and MAFLD, discusses the clinical features of various types of obesity and MAFLD, emphasizes the role of visceral obesity and insulin resistance (IR) in the development of MAFLD,and summarizes the existing treatments for obesity and MAFLD that reduce the risk of developing T2DM. [ABSTRACT FROM AUTHOR]

Purpose: Bariatric surgery (BS) has several potential metabolic benefits. However, little is known about its impact on changes in the inflammatory potential of diet and its effect on inflammatory and metabolic markers. This study aimed to assess the short-term beneficial effects of BS on dietary inflammatory potential and inflammatory and metabolic markers. Materials and Methods: Participants (n = 20) were evaluated 3 months before and after BS. Body mass, body mass index, anthropometric measurements, fat mass, fat-free mass, visceral fat, skeletal muscle mass, basal metabolic rate, serum lipids, HOMA-IR, QUICKI and inflammatory markers, including leptin, adiponectin, adiponectin/leptin ratio and plasminogen activator inhibitor-1 (PAI-1), were evaluated. Diet data were collected using a 3-day diet record and the dietary inflammatory index (DII®) and energy-adjusted dietary inflammatory index (E-DIITM) scores were computed. Results: There was a reduction in DII® (2.56 vs 2.13) and E-DIITM (2.18 vs 0.45) indicating an improvement in inflammatory nutritional profile. Moreover, there were increases in the adiponectin/leptin ratio (0.08 vs 0.21) and QUICKI scores (0.31 vs 0.37), and reductions in leptin (36.66 vs 11.41 ng/ml) and HOMA-IR scores (3.93 vs 1.50). There were also improvements in body composition and anthropometric parameters. Conclusions: BS promotes changes in metabolic profile, inflammatory state and food intake and these modifications appeared to be associated with improvements in diet-related inflammation, an increase in the adiponectin/leptin ratio and a reduction in leptin. These results contribute to knowledge on the contribution bariatric surgery can make to the treatment of obesity and the reduction of related comorbidities. [ABSTRACT FROM AUTHOR]

Background: Histological scores can estimate disease staging, allowing a standardization of the assessment of non-alcoholic fatty liver disease (NAFLD). The prediction of risk of NAFLD progression is relevant to allow the planning of interventions. Objective: To analyze the application of the Iowa NAFLD decompensation risk score, the NAFLD activity score (NAS), and steatosis-activity-fibrosis score (SAF) and to assess correlations between these scores. Methods: This is a retrospective cross-sectional study enrolling 76 individuals who underwent bariatric surgery at a tertiary university hospital. Liver biopsy was performed during procedures; histological scores were then assessed. The Iowa score was calculated using age, diabetes, and platelet count. Results: 89.5% were female and mean age was 39.1 ± 9.6 years. Mean BMI was 38.2 ± 3.7 kg/m2. Steatosis (92.1%), hepatocellular ballooning (93.4%), lobular inflammation (93.4%), and fibrosis (97.4%) were the commonest histopathological findings. According to NAS, 22.4% had definite non-alcoholic steatohepatitis (NASH). According to SAF, 89.5% had moderate or severe NAFLD. The mean risks of NAFLD decompensation at 5, 10, and 12 years were 0.8%, 2.5%, and 2.9%, respectively. The group whose risk of decompensation was above 10% comprised 2.6% and 5.3% at 10 and 12 years, respectively. The severity assessed by SAF significantly associated with definite NASH diagnosis through NAS (p < 0.001). Iowa score did not correlate with both NAS/SAF scores. Conclusion: The Iowa score demonstrated that individuals with obesity present with a significant long-term risk of NAFLD-related events. There were high rates of moderate/severe forms of NAFLD assessed by NAS and SAF scores. There were no significant correlations between Iowa and NAS/SAF scores. [ABSTRACT FROM AUTHOR]

Roux-en-Y gastric bypass surgery (RYGB) has shown efficacy in weight loss, but its role in liver fibrosis remains unknown and contentious. The present study aimed to investigate the effect of RYGB on liver fibrosis measured by non-invasive methods and assess the impact of weight loss on hepatic fibrosis in the midterm follow-up after RYGB. This longitudinal study was conducted on patients with extreme obesity, and NAFLD referred for RYGB during 2016–2018 for 3 years after their surgery. A liver biopsy was performed intraoperatively. The patient demographics, anthropometrical parameters, biochemical variables, and Liver stiffness (LS) using two-dimensional shear-wave elastography were recorded and analyzed before and in short-term and midterm follow-ups. Fifty-four patients were included with a mean age of 40.3 years; 83.3% were women. At a median follow-up of 30 months (range: 24–36 months), the excessive body mass index loss of the patients was 78.1% and, a significant reduction was seen in LS measurement. Two patients (4%) had worsening showed in the fibrosis stage, 28 (54%) no change, and 24 (42%) showed improvement, 30 months after the surgery. Moreover, the liver fibrosis stage regressed to F0 in 91% of the patients. Hepatic fibrosis resolved in the midterm follow-up in some patients whose fibrosis had progressed and deteriorated in the short-term follow-up. In addition, Liver enzymes were decreased. RYGB seems to be an effective procedure for sustained weight loss and improved liver fibrosis in EO and NAFLD patients in midterm follow-up. [ABSTRACT FROM AUTHOR]

Background and Study Aims: Weight reduction is the mainstay treatment for Nonalcoholic steatohepatitis (NASH). intragastric balloon (IGB) placement has proven benefit in terms of weight reduction. The aim of the present study is to assess the safety and efficacy of IGB placement in compensated NASH cirrhosis. Patients and Methods: Nonalcoholic steatohepatitis cirrhosis patients with CTP ≤ 7, BMI of > 30, and who were unable to achieve weight reduction with lifestyle modification in past 3 months were prospectively enrolled. Spatz3™ adjustable gastric balloon was placed endoscopically. Primary objective was to determine efficacy in weight loss at 6 months, with secondary objectives of reduction in hepatic venous pressure gradient (HVPG), liver fat (controlled attenuation parameter, CAP), liver stiffness measurement (LSM) and clinical events as well as the tolerability and adverse events due to IGB placement. Results: Altogether 56 cirrhosis patients, with a baseline BMI of 35.24 ± 3.92 and a CTP score of 6.27 ± 1.28 underwent IGB placement. The absolute weight reduction achieved was 15.88 kg (− 16.46%) and reduction in BMI was − 10.1% at 6 months. The percentage total body weight loss of ≥ 10% was achieved in 31 (55.35%) patients. The reduction in HVPG at 6-months was 11.12% (n = 16, 14.18 ± 2.12 to 12.60 ± 1.67 mmHg). The mean reduction in LSM was 28.6% and in CAP was 10.09%. Three (5.36%) patients required removal of IGB before 6-months due to persisting vomiting. No patient developed new-onset decompensation or any serious adverse event. Conclusion: IGB placement is a safe, well tolerated and effective option for reduction in weight and portal pressure in compensated obese cirrhosis patients. Trial Registry: Clinicaltrails.gov identifier no: NCT03753438. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder that is associated with abnormal accumulation of fat in the liver, which can lead to a wide variety of pathological liver defects and associated insulin resistance (IR), obesity, hypertension, dyslipidemia, diabetes, and cardiovascular disease. The molecular mechanisms that cause the initiation and progression of NAFLD are not fully understood. Increased lipolysis and de novo hepatic lipid synthesis lead to oxidative stress induced by reactive oxygen species and inflammation. Both these two entities could be interrelated and be an important mechanistic pathway, which can lead to tissue injury and hepatic cell death. Mechanisms for worsening of NAFLD include mitochondrial abnormalities, downregulation of glutathione (GSH), decreased activity of GSH-dependent antioxidants, accumulation of activated macrophages, hepatic inflammation, systemic inflammation, IR, and poorly controlled type 2 diabetes mellitus. Although no specific therapy has been approved for NAFLD, we review the latest medical therapeutics with emphasis on stem cell-based possibilities based on the presumed pathophysiology of NAFLD. [ABSTRACT FROM AUTHOR]

Purpose: Thus far, little attention has been paid to bariatric surgery (BS) in patients with severe obesity (SO) and cirrhosis with portal hypertension (PH). To address this knowledge gap, we systematically reviewed the available literature and evidence about BS in patients with SO and cirrhosis with PH. We inform on the perioperative and long-term outcomes of this intervention. Materials and Methods: Articles were identified in MEDLINE, SCOPUS, LILACS, and SCIELO, and included if they analyzed SO patients with clinically significant PH and reported the characteristics and outcomes of BS. Results: Six articles, including 32 patients, were included. The most frequent type of BS was sleeve gastrectomy performed in 27 patients. Perioperative transfusions were often not required, with only one case report describing the use of 1 unit of packed red blood cells post-operatively. Neither intraoperative nor post-op deaths were reported. All patients reported significant weight loss with improvements in comorbidities during the follow-up periods. Overall, 27 out of 29 patients had T2DM resolution, and 13 out of 23 had arterial hypertension resolution. One study reported improvements in the parameters of fibroscan. Conclusion: This systematic review described the outcomes of BS among patients with SO with cirrhosis and PH. Performing this kind of surgery among these patients appears safe and associated with acceptable perioperative and long-term outcomes. However, further studies are required to provide evidence-based, strong recommendations. [ABSTRACT FROM AUTHOR]

Obesity is a chronic disease with a complex interplay of multiple factors such as genetic, metabolic, behavioral, and environmental factors. The management of obesity includes; lifestyle modification, psychological therapy, pharmacological therapy, and bariatric surgery. To date, bariatric surgery is the most effective treatment for obesity by offering a long-term reduction in weight, remission of obesity-related complications, and improving quality of life. However, bariatric surgery is not equally effective in all patients. Thus, if we can predict who would benefit most, it will improve the risk versus benefit ratio of having surgery. In this narrative review, we explore the question on who will benefit the most from bariatric surgery by examining the recent evidence in the literature. In addition, we investigate the predisposing predictors of bariatric surgery response. Finally, we offer the best strategies in the clinic to explain the potential benefits of bariatric surgery to patients. Bariatric surgery is an effective obesity management approach. Despite its efficacy, considerable variation of individual response exists. Thus, it is important to recognize patients that will benefit most, but at present very few predictors are available which can be clinically useful. [ABSTRACT FROM AUTHOR]

Severe obesity is a strong risk factor for non-alcoholic fatty liver disease (NAFLD). Roux-en-Y gastric bypass (RYGB) surgery effectively induces weight loss, but few studies have described the long-term effects of RYGB on NAFLD-related fibrosis. Data from 220 patients with severe obesity operated by RYGB in Central Norway were analysed. Variables incorporated in NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4) index and anthropometric data were collected before surgery and a mean of 11.6 years postoperatively. FIB-4 > 1.3 or NFS > 0.675 were used as cut-off values for advanced fibrosis. Proportions with advanced fibrosis decreased from 24% to 14% assessed by FIB-4 and from 8.6% to 2.3% using NFS, with resolution rates of advanced fibrosis of 42% and 73%, respectively. The shift towards lower fibrosis categories was significant (NFS p < 0.0001; FIB-4 p = 0.002). NFS decreased from −1.32 (IQR −2.33–−0.39) to −1.71 (IQR −2.49–−0.95, p < 0.001) 11.6 years after surgery, whereas FIB-4 did not change: 0.81 (IQR 0.59–1.25) to 0.89 (IQR 0.69–1.16, p = 0.556). There were weak correlations between change in fibrosis scores and weight loss. In conclusion, the majority of patients with advanced fibrosis at baseline had improvement after 11.6 years. Factors associated with reduction in fibrosis were not identified. [ABSTRACT FROM AUTHOR]

Background: In patients with clinically severe obesity, metabolic associated fatty liver disease (MAFLD) and steatohepatitis are highly prevalent. There is a lack of prospective studies evaluating the impact of bariatric surgery (BS) on MAFLD using both noninvasive and histological criteria. The present study aims to assess the impact of BS on MAFLD using histological and biochemical criteria. Methods: This is a prospective study of 52 patients subjected to BS. Noninvasive fibrosis risk scores (NIFRS) along with anthropometric, clinical, and biochemical parameters were recorded pre- and 12 months post-BS. Liver biopsy was obtained in all individuals at baseline (wedge biopsy) and was repeated at 12 months (percutaneous Tru-cut) in those diagnosed with steatohepatitis. The primary outcome was the change in the degree of steatohepatitis and fibrosis. The secondary outcome was the change in scores for hepatocellular ballooning, lobular inflammation, steatosis, and fibrosis. Results: One year after BS, steatohepatitis resolved in core biopsies with no worsening of fibrosis in 95.7% of individuals (n = 21, 95% CI: 87.3–100), and 13 (56.5%) exhibited complete resolution. Of 15 patients with fibrosis at baseline, 13 (86.7%) showed improvement and 12 exhibited fibrosis resolution. The values of transaminases improved, but only gamma glutamyl transferase (GGT) showed statistical significance. Among the NIFRS, NAFLD fibrosis score (NFS) and Hepamet fibrosis score (HFS) showed significant improvement. Conclusions: In the setting it was studied, BS improved or resolved steatohepatitis and fibrosis in patients with obesity. NIFRS, especially NFS and HFS, and levels of GGT could be used as markers of recovery of liver function after BS. [ABSTRACT FROM AUTHOR]

Bariatric endoscopy (BE) is an emerging treatment option for people with obesity. Spin (i.e., the practice of frequent misrepresentation or overinterpretation of study findings) may lead to imbalanced and unjustified optimism in the interpretation of the results. The aim of this systematic review was to determine the frequency and type of spin in randomized controlled trials (RCTs) of endoscopic primary weight loss techniques with statistically significant and nonsignificant primary outcomes. In conclusion, spin is observed in the abstract and main text of BE reports and can lead to misinterpretation or overinterpretation of the results. Since BE challenges the available non-endoscopic treatments for obesity, further research is needed to better qualify these techniques, as being effective and safe, as well as predefined hypotheses and analyses. [ABSTRACT FROM AUTHOR]

With the recent urbanization and globalization, the adult obesity rate has been increasing, which was paralleled with a dramatic surge in the incidence and prevalence of nonalcoholic fatty liver disease (NAFLD). NAFLD poses a growing threat to human health as it represents the most common cause of chronic liver disease in developed countries. It encompasses a wide spectrum of conditions starting from a build-up of fat in hepatocytes (steatosis), to developing inflammation (steatohepatitis), and reaching up to cirrhosis. It is also associated with higher rates of cardiovascular mortalities. Therefore, proper timely treatment is essential and weight loss remains the cornerstone in the treatment of obesity-related liver diseases. When diet, exercise, and lifestyle changes are not successful, the current recommendation for weight loss includes antiobesity medications and bariatric endoscopic and surgical interventions. These interventions have shown to result in significant weight loss and improve liver steatosis and fibrosis. In the current literature review, we highlight the expected outcomes and side effects of the currently existing options to have a weight-centric NAFLD approach. [ABSTRACT FROM AUTHOR]

Introduction: Sarcopenic obesity and its association with nonalcoholic fatty liver disease (NAFLD) is under‐recognized by many healthcare providers in Western medicine due to the lack of awareness and diagnostic guidelines. The result is delayed recognition and treatment, which leads to further health deterioration and increased healthcare costs. Sarcopenic obesity is characterized by the presence of increased fat mass in combination with muscle catabolism related to chronic inflammation and/or inactivity. Previous research has recommended evaluating body composition and physical function performance to adequately diagnose sarcopenic obesity. Body composition analysis can be performed by imaging applications through magnetic resonance imaging, computed tomography, and dual‐energy x‐ray absorptiometry. Due to the cost of each device and radiation exposure for patients as evidenced in all three modalities, bioelectrical impedance analysis offers a noninvasive approach capable of providing quick and reliable estimates of lean body and fat mass. Methods and Results: This review analyzes the current evidence‐based literature, indicating a lower skeletal muscle mass and increased visceral adipose tissue correlation to the advancement of fibrosis in fatty liver disease. Conclusion: Given the substantial promising research conducted in predominantly Asian populations regarding body tissue distribution and NAFLD, additional prospective research is needed to extend these findings in Western populations. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery may be indicated in patients with nonalcoholic fatty liver disease (NAFLD) to achieve and maintain the degree of weight loss required to ensure therapeutic effects. However, bariatric surgery is still underrecognized in the treatment of NAFLD, including its inflammatory subtype, nonalcoholic steatohepatitis (NASH). Moreover, there is a lack of follow-up outcome data on different types of bariatric surgery in patients with NAFLD. This study aims to adequately assess the effect of bariatric surgery on NAFLD remission in obese patients.Methods: This prospective multicentre observational follow-up study will include 142 obese patients with NAFLD scheduled to undergo one of the following surgical procedures: sleeve gastrostomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass. The primary outcome is the complete remission rate of NAFLD one year postoperatively, which is defined by liver fat fraction < 5% on magnetic resonance imaging; the secondary outcomes includes (i) changes in NASH and liver fibrosis biopsy findings, (ii) changes in body weight and abdominal adipose weight, (iii) resolution of obesity-related comorbidities, and (iv) incidence of adverse events. A long-term follow-up related to this study will also be conducted.Discussion: This study will provide a necessary and preliminary foundation for the early identification and targeted treatment of patients with NAFLD who can be referred for bariatric surgery, as indicated for management of obesity and metabolic disease.Trial Registration: Clinicaltrials.gov: NCT04366999. Registered 21 April 2020. ( https://clinicaltrials.gov/ct2/show/NCT04366999 ). [ABSTRACT FROM AUTHOR]

The effects of bariatric procedures on nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) remain unclear. A systematic review and meta-analysis was performed to compare the impact of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on NAFLD/NASH. Patients submitted to RYGB presented significant reduction of steatohepatitis (RD: 0.53; 95% CI 0.33 to 0.74) and fibrosis (RD: 0.26; 95% CI 0.14 to 0.37). SG caused a significant reduction of steatohepatitis (RD: 0.42; 95% CI 0.27 to 0.57), but not of fibrosis (RD: 0.20; 95% CI −0.00 to 0.39). The NAFLD Activity Score was significantly improved after both procedures, as well as biochemical tests. No difference was found between RYGB and SG regarding the histopathological outcomes. SG and RYGB are equivalently effective for treating NAFLD/NASH. [ABSTRACT FROM AUTHOR]

Background: Single anastomosis sleeve ileal (SASI) bypass is a new bariatric and metabolic procedure that has both restrictive and malabsorptive effects. This study was conducted to assess both the efficacy and safety of this procedure in a short-term follow-up. Methods: This retrospective cohort study examined weight loss- and obesity-related comorbidities and complications in patients who had undergone SASI bypass from October 2017 to March 2018 at a center of excellence for bariatric/metabolic surgery. Results: Twenty-four patients had undergone SASI bypass due to some existing risk factors of gastric cancer or premalignant lesions in the esophagogastroduodenoscopy. The mean BMI of the patients was 44.2 (median 43.7, range 37.0–54.8) kg/m2. Six and 12 months after surgery, the mean (median) excessive weight loss (EWL) was 67.8% (63.3) and 86.2% (82.9) and total weight loss (TWL) was 28.5% (27.6) and 36.46% (35.8), respectively. Most patients had complete remission in type 2 diabetes mellitus (89%), arterial hypertension (86%), dyslipidemia (100%), obstructive sleep apnea (100%), and non-alcoholic fatty liver disease (73%) during the 1 year after surgery. One case of extra-luminal bleeding and one case of trocar site hernia occurred after surgery. Moreover, two patients converted to sleeve gastrectomy because of hypoalbuminemia and EWL about 1 year after SASI. Conclusion: SASI bypass is a newly introduced investigational procedure for improving weight loss and comorbidities; however, it may result in EWL and protein malnutrition and should only be performed for select patients and by well-experienced bariatric surgeons. [ABSTRACT FROM AUTHOR]

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly. It is nowadays recognized as the most frequent liver disease, affecting a quarter of global population and regularly coexisting with metabolic disorders such as type 2 diabetes, hypertension, obesity, and cardiovascular disease. In a more simplistic view, NAFLD could be defined as an increase in liver fat content, in the absence of secondary cause of steatosis. In fact, the clinical onset of the disease is a much more complex process, closely related to insulin resistance, limited expandability and dysfunctionality of adipose tissue. A fatty liver is a main driver for a new recognized liver-pancreatic α-cell axis and increased glucagon, contributing to diabetes pathophysiology. Main text: This review will focus on the clinical and pathophysiological connections between NAFLD, insulin resistance and type 2 diabetes. We reviewed non-invasive methods and several scoring systems for estimative of steatosis and fibrosis, proposing a multistep process for NAFLD evaluation. We will also discuss treatment options with a more comprehensive view, focusing on the current available therapies for obesity and/or type 2 diabetes that impact each stage of NAFLD. Conclusion: The proper understanding of NAFLD spectrum—as a continuum from obesity to metabolic syndrome and diabetes—may contribute to the early identification and for establishment of targeted treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to present and compare anthropometric characteristics of Roma pregnant women in Virovitica-Podravina County to the majoritarian non-Roma group. A retrospective study on deliveries of Roma women at the Maternity Ward of the General Hospital Virovitica, Croatia, was carried out in the period from 1991 to 2010. The study included 204 Roma and 408 non-Roma pregnant women. The values analysed were prepregnancy body weight and height, body mass index (BMI), body weight before delivery, gestational weight gain (GWG) and external dimensions of the pelvis. Roma women give birth while being on average younger, 7.6 cm smaller, 4.70 kg lighter at the beginning and 5.13 kg at the end of the pregnancy, compared to the non-Roma women. The values of BMI and GWG are similar in both groups, however a higher frequency of the underweight, overweight and obese pregnant women was found in the Roma group. All three outer dimensions of the pelvis (Distancia cristarum, spinarum and trochanterica) are on average 1 cm smaller in Roma group. The differences in anthropometric characteristics between Roma and non-Roma pregnant women in Virovitica-Podravina County can be explained by ethnical origin, interaction with environmental factors and lifestyle. [ABSTRACT FROM AUTHOR]

Background: To evaluate vitamin B12 and folate status in pregnancy and their relationship with maternal obesity, gestational diabetes mellitus (GDM), and offspring birthweight. Methods: A retrospective case-control study of 344 women (143 GDM, 201 no-GDM) attending a district general hospital and that had B12 and folate levels measured in the early 3rd trimester was performed. Maternal history including early pregnancy body mass index (BMI) and neonatal data (birthweight, sex, and gestational age) was recorded for all subjects. Results: 26% of the cohort had B12 levels <150 pmol/L (32% vs. 22% in the two groups respectively, p < 0.05) while 1.5% were folate deficient. After adjusting for confounders, 1st trimester BMI was negatively associated with 3rd trimester B12 levels. Women with B12 insufficiency had higher odds of obesity and GDM (aOR (95% CI) 2.40 (1.31, 4.40), p = 0.004, and 2.59 (1.35, 4.98), p = 0.004, respectively), although the latter was partly mediated by BMI. In women without GDM, the lowest quartile of B12 and highest quartile of folate had significantly higher adjusted risk of fetal macrosomia (RR 5.3 (1.26, 21.91), p = 0.02 and 4.99 (1.15, 21.62), p = 0.03 respectively). Conclusion: This is the first study from the UK to show that maternal B12 levels are associated with BMI, risk of GDM, and additionally may have an independent effect on macrosomia. Due to the increasing burden of maternal obesity and GDM, longitudinal studies with B12 measurements in early pregnancy are needed to explore this link. [ABSTRACT FROM AUTHOR]

This study aimed to examine the effect of lifestyle intervention on the risk of gestational diabetes mellitus (GDM). We searched PubMed, Springer and other databases to retrieve articles published in English and Chinese up to 30 September 2015. The inclusion criteria were randomized controlled trials evaluating the effects of lifestyle intervention on risk of GDM. Exclusion criteria were studies with prepregnancy diabetes mellitus or interventions with nutrient supplements. Random-effect and fixed-effect model analyses were used to obtain pooled relative risks and 95% confidence intervals (CIs) of diet and physical activity on the risk of GDM. Subgroup analyses were performed to check the consistency of effect sizes across groups where appropriate. We identified 29 randomized controlled trials with 11,487 pregnant women, addressing the effect of lifestyle intervention on the risk of GDM. In the pooled analysis, either diet or physical activity resulted in an 18% (95%CI 5-30%) reduction in the risk of GDM ( P = 0.0091). Subgroup analysis showed that such intervention was effective among women with intervention before the 15th gestational week (relative risk: 0.80, 95%CI 0.66-0.97), but not among women receiving the intervention afterwards. We conclude that lifestyle modification during pregnancy, especially before the 15th gestational week, can reduce the risk of GDM. © 2016 World Obesity [ABSTRACT FROM AUTHOR]

Background: Large for gestational age infants have an increased risk of obesity, cardiovascular and metabolic complications during life. Knowledge of the key predictive factors of neonatal adiposity is required to devise targeted antenatal interventions. Our objective was to determine the fetal metabolic factors that influence regional neonatal adiposity in a cohort of women with previous large for gestational age offspring.Methods: Data from the ROLO [Randomised COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analysed in the ROLO Kids study. Neonatal anthropometric and skinfold measurements were compared with fetal leptin and C-peptide results from cord blood in 185 cases. Analyses were performed to examine the association between these metabolic factors and birthweight, anthropometry and markers of central and generalised adiposity.Results: Fetal leptin was found to correlate with birthweight, general adiposity and multiple anthropometric measurements. On multiple regression analysis, fetal leptin remained significantly associated with adiposity, independent of gender, maternal BMI, gestational age or study group assignment, while fetal C-peptide was no longer significant.Conclusion: Fetal leptin may be an important predictor of regional neonatal adiposity. Interventional studies are required to assess the impact of neonatal adiposity on the subsequent risk of childhood obesity and to determine whether interventions which reduce circulating leptin levels have a role to play in improving neonatal adiposity measures. [ABSTRACT FROM AUTHOR]

The conventional aetiological model of obesity and diabetes proposes a genetic predisposition and a precipitation by an unhealthy adult lifestyle. This hypothesis was challenged by David Barker who proposed that the intrauterine environment influences the risk of non-communicable diseases (NCDs). The original idea was based on fetal undernutrition because lower birth weight was associated with a higher risk of diabetes and heart disease. However, soon it was clear that the association was U shaped, and that the increased risk in large babies was driven by maternal obesity and diabetes. A number of human and animal studies have refined our ideas of 'fetal programming', which is now thought to be related to acquired chemical changes in DNA (methylation), histones (acetylation and other) and the role of non-coding miRNAs. Maternal nutritional disturbances are the major programming stimulus, in addition to a deranged metabolism, infections, maternal stress, extreme atmospheric temperature, etc. The first demonstration of a link between fetal 'starvation' and future ill-health was in the Dutch Hunger Winter studies. In the prospective Pune Maternal Nutrition Study, we found that small and thin Indian babies were more adipose compared to larger English babies, and their higher risk of future diabetes was reflected in higher insulin and leptin and lower adiponectin concentrations in the cord blood. This phenotype was partly related to a deranged 1-carbon metabolism due to an imbalance in vitamin B12 (low) and folate (high) nutrition, which was also related to insulin resistance in the offspring. Maternal obesity and diabetes have made an increasing contribution to childhood obesity and diabetes at a young age. This was prominently shown in Pima Indians but is now obvious in all other populations. The best window of opportunity to prevent fetal programming of NCDs is in the periconceptional period. This is the period when gametogenesis, fertilisation, implantation, embryogenesis and placentation occur. Improving the nutrition and the health of young girls could make a substantial contribution to reducing the rapidly rising epidemic of NCDs in the world. This is referred to as 'primordial' prevention. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. In low- and middle-income countries, the distribution of childhood nutritional diseases is shifting from a predominance of undernutrition to a dual burden of under- and overnutrition. This novel and complex problem challenges governments and health organizations to tackle opposite ends of the malnutrition spectrum. The dual burden may manifest within a community, household, or individual, but these different levels have not been addressed collectively. Objective. To critically review literature on the prevalence, trends, and predictors of the dual burden, with a focus on children from birth to 18 years of age. Methods. We reviewed literature since January 1, 1990, published in English, using the PubMed search terms nutrition transition, double burden, dual burden, nutrition status, obesity, overweight, underweight, stunting, body composition, and micronutrient deficiencies. The findings were classified and described according to dual burden level (community, household, or individual). Results. Global trends indicate decreases in diseases of undernutrition, while overnutrition is increasing. On the community level, economic status may influence the extent of the dual burden, with obesity increasingly affecting the already undernourished poor. In a household, shared determinants of poor nutritional status among members can result in disparate nutritional status across generations. Within an individual, obesity may cooccur with stunting or anemia due to shared underlying determinants or physiologic links. Conclusions. The dual burden of malnutrition poses a threat to children's health in low- and middle-income countries. We must remain committed to reducing undernutrition while simultaneously preventing overnutrition through integrated child health programs that incorporate prevention of infection, diet quality, and physical activity. [ABSTRACT FROM AUTHOR]

Background: People who originate from the Indian subcontinent (South Asians) suffer among the highest rates of type 2 diabetes in the world. Prior evidence suggests that metabolic risk factors develop early in life and are influenced by maternal and paternal behaviors, the intrauterine environment, and genetic factors. The South Asian Birth Cohort Study (START) will investigate the environmental and genetic basis of adiposity among 750 South Asian offspring recruited from highly divergent environments, namely, rural and urban India and urban Canada. Methods: Detailed information on health behaviors including diet and physical activity, and blood samples for metabolic parameters and DNA are collected from pregnant women of South Asian ancestry who are free of significant chronic disease. They also undergo a provocative test to diagnose impaired glucose tolerance and gestational diabetes. At delivery, cord blood and newborn anthropometric indices (i.e. birth weight, length, head circumference and skin fold thickness) are collected. The mother and growing offspring are followed prospectively and information on the growth trajectory, adiposity and health behaviors will be collected annually up to age 3 years. Our aim is to recruit a minimum of 750 mother-infant pairs equally divided between three divergent environments: rural India, urban India, and Canada Summary: The START cohort will increase our understanding of the environmental and genetic determinants of adiposity and related metabolic abnormalities among South Asians living in India and Canada. [ABSTRACT FROM AUTHOR]

Background: Treatment options for NAFLD are still limited. Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB), has been shown to improve metabolic and histologic markers of NAFLD. Glucagon-like-peptide-1 (GLP-1) analogues lead to improvements in phase 2 clinical trials. We directly compared the effects of RYGB with a treatment using liraglutide and/or peptide tyrosine tyrosine 3-36 (PYY3-36) in a rat model for early NAFLD. Methods: Obese male Wistar rats (high-fat diet (HFD)-induced) were randomized into the following treatment groups: RYGB, sham-operation (sham), liraglutide (0.4 mg/kg/day), PYY3-36 (0.1 mg/kg/day), liraglutide+PYY3-36, and saline. After an observation period of 4 weeks, liver samples were histologically evaluated, ELISAs and RNA sequencing + RT-qPCRs were performed. Results: RYGB and liraglutide+PYY3-36 induced a similar body weight loss and, compared to sham/saline, marked histological improvements with significantly less steatosis. However, only RYGB induced significant metabolic improvements (e.g., adiponectin/leptin ratio 18.8 ± 11.8 vs. 2.4 ± 1.2 in liraglutide+PYY3-36- or 1.4 ± 0.9 in sham-treated rats). Furthermore, RNA sequencing revealed a high number of differentially regulated genes in RYGB treated animals only. Conclusions: The combination therapy of liraglutide+PYY3-36 partly mimics the positive effects of RYGB on weight reduction and on hepatic steatosis, while its effects on metabolic function lack behind RYGB. [ABSTRACT FROM AUTHOR]

Being overweight is associated with pregnancy-related disorders such as gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and excessive maternal weight gain (MWG). Exercise and metformin reduce the risk of these disorders. This network meta-analysis (NMA) aims to compare the effect of metformin and different types of exercise (aerobic, resistance and combined) on the risk of GDM, HDP, and MWG among overweight/obese pregnant women. Medline, EMBASE, Web of Science and Cochrane Library were searched from inception to June 2021. Meta-analyses and NMAs were performed. Sixteen randomized controlled trials were included. In the NMA, aerobic exercise showed an effect on GDM (RR = 0.51, 95% CI = 0.26, 0.97), and metformin a reduction in MWG (MWG = −2.93 kg, 95% CI = −4.98, −0.87). No intervention showed any effect on the reduction of HDP. Our study suggests that aerobic exercise may have the greatest effect in reducing the risk of GDM, and perhaps, the MWG. Strategies should be developed to increase adherence to this type of intervention among overweight women without contraindications. Although metformin could reduce MWG, medicalization of pregnancy in healthy women is not justified with the present results. More research is needed on the effect of the intensity and frequency of exercise sessions and the length of interventions. [ABSTRACT FROM AUTHOR]

Bariatric surgery leads to sustained weight loss and the resolution of obesity-related comorbidities. Recent studies have suggested that changes in gut microbiota are associated with the weight loss induced by bariatric surgery. Several studies have observed major changes in the microbial composition following gastric bypass surgery. However, there are inconsistencies between the reported alterations in microbial compositions in different studies. Furthermore, it is well established that diet is an important factor shaping the composition and function of intestinal microbiota. However, most studies on gastric bypass have not assessed the impact of dietary intake on the microbiome composition in general, let alone the impact of restrictive diets prior to bariatric surgery, which are recommended for reducing liver fat content and size. Thus, the relative impact of bariatric surgery on weight loss and gut microbiota remains unclear. Therefore, this review aims to provide a deeper understanding of the current knowledge of the changes in intestinal microbiota induced by bariatric surgery considering pre-surgical nutritional changes. [ABSTRACT FROM AUTHOR]