Severe Obesity Research Articles

P-641 A prospective observational case series on the effects of a very low-calorie ketogenic diet (VLCKD) in overweight and obese infertile women

Abstract Study question What is the compliance level of overweight/obese infertile patients to VLCKD? Is therapeutic adherence associated with weight loss and increased pregnancy rates? Summary answer Compliance level to VLCKD was surprisingly high. Participants experienced weight loss and pregnancy rates improved. What is known already Obesity and overweight are associated with infertility. They can adversely affect the hypothalamic-pituitary-gonadal axis, compromise oocyte quality and reduce endometrial receptivity. In addition, obesity exposes women at increased risk of obstetric complications. Although not always consistent, some evidence suggests a beneficial effect of diet in this setting, both for natural conception and in the context of ART. However, these studies also show low compliance, with many patients failing to lose enough weight to be clinically significant. VLCKD is a more aggressive approach to treating severe obesity and may represent a more effective option for these patients. Study design, size, duration This case-series prospective study has been performed at Unit of Obesity and Occupational medicine, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico Milano between May 2019 and September 2023 and involved 42 infertile women aged ≤ 40 years, affected by overweight-obesity (BMI 27.5-35), but without other relevant systemic pathologies. Participants/materials, setting, methods Treatment firstly included 3 months of VLCKD followed by 12 months of Low-Calorie Diet (LCD). The occurrence of any natural pregnancy led to the discontinuation of treatment. These cases were counted as successes. Throughout the study period, patients underwent regular dietary and anthropometric evaluations. Main results and the role of chance Of the 42 recruited patients, 36 adhered to the VLCKD. The median treatment duration was 5.5 months [Interquartile Range (IQR) 3-9]. The compliance rate was 86% (95% CI: 72-93%). A significant reduction in BMI was observed: at recruitment, patients had a median BMI of 36.6 [IQR 33.4-39.9], and at the end, it was 29.5 [IQR 27.3-32.7], with a weight loss of 19.9 kg [IQR 12.7-24.4]. Regarding pregnancy, 8 women (22%) achieved a natural pregnancy, while of the remaining 28 patients, 25 underwent ART treatments. Among these, 16 achieved pregnancy (13 by homologous cycles, two donor cycles, and one with ovulation induction). In total, 24 women achieved pregnancy. The intention-to-treat success rate was 57% (95% CI: 42-71%), and the protocol success rate was 67% (95% CI: 50-80%). Limitations, reasons for caution The case-series study design, by definition, does not require a control group and this could be considered a “weakness”. However, it should be noted that patients were likely to be highly motivated to lose weight and health-conscious, thus creating a sample group with distinctive characteristics. Wider implications of the findings The use of VLCKD in obese infertile women allows high compliance to be achieved. The probability of pregnancy also appears very promising. VLCKD could be considered as a first approach for the treatment of obese women who do not have contraindications to ketosis. Trial registration number not applicable

Obesity is associated with lower levels of negative emotions in polycystic ovary syndrome in clinical and animal studies

Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in women of reproductive age. It is frequently comorbid with obesity and negative emotions. Currently, there are few reports on the relationship between obesity and negative emotions in patients with PCOS. Here we performed both basic and clinical studies to study the relationship between obesity and negative emotions in PCOS. Methods We performed a cross-sectional study including 608 patients with PCOS and 184 healthy participants to assess the mental health status of people with different body mass indices (BMI). Self-rated anxiety, depression, and perceived stress scales were used for subjective mood evaluations. Rat PCOS models fed 45 and 60% high-fat diets were used to confirm the results of the clinical study. Elevated plus maze and open field tests were used to assess anxiety- and depression-like behaviors in rats. Results We observed overweight/obesity, increased depression, anxiety, and perceived stress in women with PCOS, and found that anxiety and depression were negatively correlated with BMI in patients with severe obesity and PCOS. Similar results were confirmed in the animal study; the elevated plus maze test and open field test demonstrated that only 60% of high fat diet-induced obesity partly reversed anxiety- and depression-like behaviors in PCOS rats. A high-fat diet also modulated rat hypothalamic and hippocampal luteinizing hormone and testosterone levels. Conclusion These results reveal a potential relationship between obesity and negative emotions in PCOS and prompt further investigation. The interactions between various symptoms of PCOS may be targeted to improve the overall well-being of patients.

When It Rains It Pours...: Wernicke Encephalopathy with Sudden Blindness after Bariatric Surgery in a Patient with Congenital Deafness.

Malabsorption syndromes are known chronic complications of bariatric surgery. Therefore, it is recommended to take oral supplementation with multivitamins. Wernicke's encephalopathy represents an acute neuropsychiatric syndrome associated with alcoholism or severe malnutrition; sporadic cases of this potential complication related to bariatric surgery are described in the literature. We present a case of Wernicke's encephalopathy due to severe vitamin B1 deficiency after bariatric surgery. A 31-year-old woman with deaf-mutism from the age of 3 years old, operated 3 months before with a mini-gastric bypass for severe obesity, was transferred to our unit after accessing the emergency room. In the immediate medical history, there was the sudden and rapid decline in vision, leading to complete loss of vision, marked asthenia, and paresthesia in the four limbs. Considering the previous bariatric surgery, the diagnosis of non-alcoholic Wernicke's syndrome was suspected, for which IV therapy with Vitamin B1 was started at a dosage of 5 vials of 200 mg in 100 cc of saline solution (three times a day for the first 72 hours, subsequently 1 once/day). After 12 hours, there was an improvement in visual acuity, and the symptoms completely resolved within 48 hours. She was discharged with complete resolution of all symptoms after 1 month. Initial vision loss without confusion or encephalopathy is one atypical presentation of Wernicke syndrome. Clinical suspicion must be high in case of alcoholism or post-bariatric surgery. Early recognition of atypical symptoms, including vision loss, and timely administration of therapy improves the prognosis of this potentially reversible but time-dependent neurological emergency.

Which components of behavioral weight management programs are essential for weight loss in people living with obesity? A rapid review of systematic reviews.

The optimal treatment and organization of care for people with obesity is one of the greatest challenges facing today's health services. While surgery and pharmacotherapy offer effective treatment options for some people with obesity, behavioral interventions are important to support long-term behavioral change. However, little is known about the most effective components of behavioral interventions, and this is especially the case for people with complex or severe obesity (i.e. body mass index [BMI] > 35 kg/m2). Accordingly, the current rapid review aimed to identify which behavior change techniques (BCTs) are effective for weight loss in adults with (severe) obesity. A secondary aim was to review the effects of BCTs on dietary behaviors and physical activity, and psychological outcomes, recognizing that behavioral interventions commonly target these. A search of Scopus, Ovid Medline, and Web of Science resulted in 1227 results, with 22 reviews eligible for inclusion. The most commonly reported BCTs were self-monitoring and goal setting, but these had variable effects on weight in adults with obesity. Combining these BCTs with other self-regulatory techniques led to increased weight loss. Further, for adults with severe obesity, so-called 'nudge' techniques and self-regulatory techniques were associated with greater weight loss. Three reviews also found that while self-monitoring increased physical activity, behavioral commitments increased changes to dietary behaviors. BCTs were not associated with psychological well-being. The review confirms that behavioral interventions have an impact in weight management, including for individuals with more complex or severe obesity, but highlights the need for further investigation of their use within clinical settings.

High prevalence of dysfunctional uterine bleeding in candidates for metabolic/bariatric surgery: increased endometrial cancer risk?

BackgroundEndometrial cancer (EC) is the strongest obesity-associated malignancy and the fastest-growing cancer in young women. Early identification of EC and other endometrial pathology (malignant and nonmalignant) in women with severe obesity may improve treatment options and uterine preservation. Screening for endometrial pathology using abnormal or postmenopausal uterine bleeding (APUB) as a surrogate in women pursuing metabolic/bariatric surgery may be clinically beneficial, but data supporting this effort are limited. ObjectiveTo develop and institute a screening program for APUB as a surrogate for endometrial pathology in bariatric surgery candidates. SettingTwo, academic metabolic/bariatric surgery programs in Louisiana, United States. MethodsThe Modified SAMANTA is a 10-item questionnaire that was implemented to identify patients with APUB, specifically combining tools designed to identify anovulatory/postmenopausal and heavy menstrual bleeding. Demographic (age, race), body mass index, and questionnaire data were analyzed with respect to positive screening using data from March 2021 through May 2023. ResultsOf 1371 eligible women presenting for surgical evaluation, 664 (48.4%) positive screens were identified and referred for gynecologic evaluation to rule out endometrial hyperplasia/cancer or other endometrial pathology. The likelihood of positive screening for APUB was associated with increasing BMI (P = .001) and Black/African American race (P = .003), as well as increasing SAMANTA score (P < .001). In contrast, risk of positive screening was negatively associated with increasing age (P < .001). ConclusionsWomen presenting for metabolic/bariatric surgery have a high prevalence of APUB and, given this dysfunctional bleeding and concurrent obesity, are at greater risk for underlying EC. Potential risk factors for APUB, given their associations with screening positive, include increased body mass index, younger age, and Black/African American race. Standardized screening with appropriate gynecologic referral should be a routine part of the overall evaluation for women with severe obesity.

Severe obesity is associated with worse outcomes than lean metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in people with obesity. We aimed to study the association of body mass index (BMI) with clinical outcomes in patients with MASLD. A retrospective cohort of 32,900 patients with MASLD, identified through the International Classification of Diseases-9 and 10 codes within the electronic health records of a large US-based health system, with a mean follow-up of 5.5 years (range: 1-15y), was stratified into 6 BMI categories, <25, 25-<30, 30-<40, 40-<50, and ≥50kg/m2. The risk of liver decompensation and extrahepatic obesity-associated cancers had a J-shaped profile (both ps for linear and quadratic terms <0.05). Compared to patients with BMI 25-<30kg/m2, the adjusted HRs (95% CIs) for liver decompensation of patients with BMI <25 and BMI ≥50kg/m2 were 1.44 (1.17-1.77) and 2.27 (1.66-3.00), respectively. The corresponding figures for obesity-associated extrahepatic cancer were 1.15 (0.97-1.36) and 1.29 (1.00-1.76). There was an inverse association for BMI with liver transplantation and non-obesity-associated cancer (both ps for linear terms <0.05), but no association with HCC or all types of cancers combined. A similar J-shaped association between BMI and all-cause mortality was observed; adjusted HRs (95% CIs) for BMI <25 and ≥50kg/m2 were 1.51 (1.32-1.72) and 3.24 (2.67-3.83), respectively, compared with BMI 25-<30kg/m2 (both ps for linear and quadratic terms <0.001). Patients with MASLD and very severe obesity (BMI ≥50kg/m2) had the highest risk, exceeding that of patients with lean MASLD, for developing liver decompensation, obesity-associated extrahepatic cancers, or dying from any cause.

Cancer incidence following bariatric surgery in renal transplant recipients: a retrospective multi-center analysis

BackgroundObesity, a known independent risk factor for developing malignancy. Additionally, renal transplant recipients (RTR) confer a 2- to 4-fold increased risk of overall malignancies with an excess absolute risk of .7% per year. While transplant recipients are at risk for obesity and malignancy, the effect of bariatric surgery (BS) in the posttransplantation setting is not well known. ObjectivesOur study primarily evaluated the impact of BS on cancer incidence in RTR with severe obesity in the posttransplantation setting. Weight loss outcomes were analyzed secondarily. SettingUniversity Hospital. MethodsA retrospective study using TriNetX database was developed to analyze cancer outcomes in RTR with posttransplantation BS versus RTR without BS from 2000 to 2023. After the exclusion process and propensity matching, both cohorts consisted of 153 patients. ResultsRTR-BS had a significantly lower incidence of overall cancer and transplant-related cancers (P < .05). No significant difference was identified in cutaneous, gastrointestinal, and reproductive cancers. Percent Excess Weight Loss (%EWL) was significantly lower in RTR-only cohort (11.4%) versus RTR-BS cohort (57.8%) at 5 years. Sleeve gastrectomy (SG) patients (73.19%) had significantly higher %EWL than Roux en-Y gastric bypass (RYGB) patients (49.33%) at 3 years. No difference in cancer incidence was noted between SG and RYGB patients. ConclusionPostrenal transplantation BS had a diminishing effect on overall and transplant-related cancer incidence in RTR with severe obesity. Significant weight loss was also demonstrated with post-renal transplantation BS.

Phaseolus vulgaris Extract Combined With a Low-Calorie Diet Positively Modulates Gut Microbial Ecosystem in Subjects With Severe Obesity: A Randomized Controlled Trial

Phaseolus vulgaris Extract Combined With a Low-Calorie Diet Positively Modulates Gut Microbial Ecosystem in Subjects With Severe Obesity: A Randomized Controlled Trial

Obesity and Severe Obesity Among Children Aged 24 to 48 Months Participating in the WIC Infant and Toddler Feeding Practices Study-2 by Race/Ethnicity

Obesity and Severe Obesity Among Children Aged 24 to 48 Months Participating in the WIC Infant and Toddler Feeding Practices Study-2 by Race/Ethnicity

Integrator complex subunit 6 promotes hepatocellular steatosis via β-catenin-PPARγ axis

Hepatic adipogenesis has common mechanisms with adipocyte differentiation such as PPARγ involvement and the induction of adipose tissue-specific molecules. A previous report demonstrated that integrator complex subunit 6 (INTS6) is required for adipocyte differentiation. This study aimed to investigate INTS6 expression and its role in hepatic steatosis progression. The expression of INTS6 and PPARγ was examined in the liver of a mouse model of steatohepatitis and in paired liver biopsy samples from 11 patients with severe obesity and histologically proven metabolic dysfunction associated steatohepatitis (MASH) before and one year after bariatric surgery. To induce hepatocellular steatosis in vitro, an immortalized human hepatocyte cell line Hc3716 was treated with free fatty acids. In the steatohepatitis mouse model, we observed hepatic induction of INTS6, PPARγ, and adipocyte-specific genes. In contrast, β-catenin which negatively regulates PPARγ was reduced. Biopsied human livers demonstrated a strong positive correlation (r2 = 0.8755) between INTS6 and PPARγ mRNA levels. After bariatric surgery, gene expressions of PPARγ, FABP4, and CD36 were mostly downregulated. In our in vitro experiments, we observed a concentration-dependent increase in Oil Red O staining in Hc3716 cells after treatment with the free fatty acids. Alongside this change, the expression of INTS6, PPARγ, and adipocyte-specific genes was induced. INTS6 knockdown using siRNA significantly suppressed cellular lipid accumulation together with induction of β-catenin and PPARγ downregulation. Collectively, INTS6 expression closely correlates with PPARγ. INTS6 suppression significantly reduced hepatocyte steatosis via β-catenin-PPARγ axis, indicating that INTS6 could be a novel therapeutic target for treating MASH.

Anesthesia considerations for pediatric metabolic and bariatric surgery

Childhood obesity is a rapidly growing global health issue, linked to significant lifelong morbidity and mortality. Its impact on various organ systems increases perioperative complications. Obesity treatment in children and adolescents involves lifestyle, dietary, and behavioral modifications, as well as pharmacologic interventions that targets hormonal, metabolic, and neurochemical abnormalities. Metabolic and bariatric surgery, proven safe and effective for adults with severe obesity (class 2 or higher), is now being recommended for adolescents. Key anesthetic considerations for these surgeries include preoperative optimization, advanced airway management, targeted ventilation strategies, and opioid-sparing analgesic regimens. Comprehensive presurgical evaluations must address co-morbid conditions such as hypertension, obstructive sleep apnea, asthma, and impaired glycemic control. Preoperative management should also consider the effects of antiobesity medications on gastric emptying and hemodynamic stability. Ventilation strategies should prevent atelectasis while avoiding barotrauma, and drug dosages must be adjusted for altered pharmacokinetics due to increased adipose tissue. Employing enhanced recovery after surgery protocols may reduce perioperative complications, shorten postsurgical stays, and improve outcomes.

Retention and transition to adult health care in adolescent bariatric surgery

The American Society of Metabolic and Bariatric Surgery (ASMBS) and the American Academy of Pediatrics (AAP) recommend bariatric surgery as a treatment option for severe obesity. Bariatric surgery results in weight loss and improves obesity-related comorbidities. After surgery, adolescents and young adults require close observation and interdisciplinary care to help optimize weight loss, minimize nutrient deficiencies, address mental or physical health complications, and ensure a smooth transition to adult care. Yet, the extant literature on adherence and transition of care in bariatric programs is limited. Using 3 case studies from 2 bariatric programs, one on retention and 2 on transition of care, this paper highlights learning opportunities for care delivery after bariatric surgery. A quality improvement framework and an embedded electronic medical health registry can improve retention rates within a bariatric program. In addition, implementing a workflow ensures standardization of care; however, a key challenge is inadequate staffing. The programs established a transition of care policy and protocol by incorporating several of the Six Core Elements, a recognized guide for ensuring a safe and appropriate transfer from pediatric to adult care. Several research gaps remain, and further work is needed to determine and standardize best practices for adolescent bariatric surgery.

Obesity and the Need for Bariatric Surgery in Nigeria: A Review.

Obesity was mainly regarded as a disease of developed countries, but currently there is a growing rise in the population of patients with obesity in developing countries of Africa. A body mass index of 30 kg/m2 or higher is regarded as obesity, and this may be associated with comorbidities such as metabolic and cardiovascular diseases, orthopaedic and psychiatric conditions, and cancer. There is conclusive scientific evidence that shows that obesity is caused by complex psychosocial, genetic and environmental factors. Diet and exercise are not effective as sole management of severe obesity. Bariatric surgery is the most cost-effective definitive treatment for all classes of obesity, and the associated weight reduction causes improvement or complete resolution of obesity-associated comorbidity, improves the quality of life and reduces all-cause mortality. It is estimated that about 15% of adults in Nigeria are obese, and in the year 2023, it was reported that only 214 bariatric procedures were done locally, with 134 (62.6%) being gastric balloon insertions, 75 (35.1%) primary weight loss surgeries and 5 revisional surgeries (2.3%). In this article, we discussed the existing weight loss options in Nigeria, the current state of bariatric surgery and the need to improve the practice of bariatric surgery for obese Nigerians and complications of obesity.

Usability of the BigO system in pediatric obesity treatment: A mixed-methods evaluation of clinical end-users

ObjectiveTo assess technical usability of the BigO app and clinical portal among diverse participants and explore the overall user experiences of both. MethodsMethods included technical usability testing by measuring the relative user efficiency score (RUS) for the app and measuring Relative User Efficiency (RUE) using the ‘think aloud’ method with the clinical portal. Qualitative approaches involved focus groups with adolescent app users and semi-structured one-to-one interviews with clinician participants. Thematic analysis was applied to analyze qualitative data. ParticipantsClinical participants consisted of adolescents seeking treatment for severe obesity and were invited via telephone/face to face to attend technical usability testing and a focus group. Healthcare professionals (HCPs) and researchers using the BigO clinical portal interface were invited to participate in usability testing and semi-structured interviews. ResultsFrom 14 families invited to attend, seven consented to join the study and four adolescents (mean age=13.8 (SD 0.8) years) participated. Additionally, six HCPs and one pediatric obesity researcher took part. RUS for adolescents indicated that the tasks required of them via myBigO app were feasible, and technically efficient. No user-related errors were observed during tasks. Technical barriers reported by adolescents included notifications of battery optimization, misunderstanding image annotation language, and compatibility challenges with certain phone models. RUS for the HCPs and researcher indicated that basic technical skills are a potential barrier for clinical portal use and qualitative findings revealed that clinical users wanted a logging option for monitoring goals and providing feedback on the portal. ConclusionOur study provided valuable formative findings from clinical end-users in Ireland indicating that adolescents being treated for obesity rated myBigO app as usable, acceptable and that it may assist other key stakeholders to understand food marketing and to monitor dietary and physical activity behaviors. Several key suggestions for future iterations of the clinical portal were provided to enhance its value in pediatric obesity treatment.

Improving Obesity Outcomes in an Academic Clinic: A Quality Improvement Study

Introduction: Obesity is a chronic disease that affects more than 40% of the population in the United States. The prevalence of severe obesity doubled in the past two decades. Primary care providers are usually the first to screen patients for obesity. According to a 2018 study. Only 55% of adults with obesity were reported to have received the diagnosis of obesity and less than a third of the patients followed up for an obesity-specific visit. The management of obesity is multifactorial with lifestyle modifications and pharmacological and psychological therapies. In our academic clinic, there was a gap in comprehensive satisfactory obesity counseling, which addresses lifestyle modifications and adjunctive pharmacological therapies. Addressing this gap with an obesity-specific visit helps clinicians to discuss available options to manage obesity. Improvement in body weight is linked with improved control of hypertension, diabetes, and heart disease leading to improved health outcomes. Aim: To improve obesity counseling rates and usage of standardized obesity templates in an academic clinic by 25% in 3 months. Method: We used the IHI model of improvement using the plan-do-study-act framework to test changes on a small scale and guide the quality improvement study. To better address our aim, we divided our QI project into 2 cycles. For PDSA-1, a thorough chart search for the last 3 months was done to calculate a baseline obesity counseling rate. A root-cause analysis was completed with multi-disciplinary input from faculty, clinic staff, and residents, and several existing barriers that preclude satisfactory obesity counseling were identified. Proposed interventions corresponding to each root cause were plotted on an impact effort matrix. Interventions with the least effort and the most impact were selected as proposed solutions. These included creating a short education session on obesity management and creating an obesity counseling template. Post-intervention, the obesity counseling rates and use of the template were recorded on a run chart. For PDSA-2, we introduced an obesity assessment and plan (A/P) template, with the goal to incorporate all aspects of obesity management, i.e., lifestyle modification, diet, exercise, and screening for disease related co-morbidities. Results: Satisfactory obesity counseling prior to intervention was 32%. The first PDSA cycle post-intervention showed an improvement in the obesity counseling rates to 56%. About 20% of the clinic notes for the counseled patients used the proposed template. About 8% of the counseled patients agreed to a separate obesity-specific visit. The second PDSA cycle showed 20.1% usage of the standardized A/P plan template. In the group that the template was used, there was 63.6% reduction in BMI; compared to 39.4% BMI reduction in group without template usage. (OR= 2.34, p=0.034. Next steps: We noted an overall improvement in the obesity counseling rates after our interventions. However, we noticed that the A/P template usage did not meet our goal of 25% usage. We will conduct multidisciplinary team meetings to understand measures that can be undertaken to improve usage of A/P template. Patients will also be encouraged to have an obesity-specific visit.

Class 3 Obesity and Oral Health in Adults: A Scoping Review of the Challenges for Oral Healthcare Services.

Background: Obesity is one of the most neglected public health problems affecting both developed and developing countries. The most clinically severe obesity (Class 3 obesity) has both clinical and service delivery implications on dental services. However, associations between Class 3 obesity and oral health are minimally explored in the literature and thus poorly understood. Aims: This scoping review aimed to explore the existing evidence on Class 3 obesity and oral health. Methods: A literature search was performed via Medline, Scopus, Google scholar and Embase research databases. Results: A total of 375 papers were sourced from the database search. Twenty seven full-text papers were included in the final literature review. Results revealed findings from both quantitative and qualitative studies. Papers included results pertaining to associations with dental disease, oral health and associated behaviours, oral health-related quality of life and the barriers experienced by adults with Class 3 obesity in accessing dental services. Conclusions: While mixed findings were identified, this scoping review reports associations between Class 3 obesity and poor oral health across various domains including clinical parameters and oral health related quality of life. The literature has also highlighted important barriers to dental care in those with the most severe Class 3 obesity. Based upon our findings, we have summarised current oral health management implications and directions for future research.

Elevated Plasma Levels of Growth Arrest Specific 6 (Gas6) Protein in Severe Obesity: Implications for Adipose Tissue and Inflammation.

BACKGROUND Preliminary data suggest an adipogenic role for growth arrest-specific 6 (Gas6), a pleiotropic molecule involved in inflammation, proliferation, and hemostasis through its Tyro3, Axl, and MerTK (TAM) receptors. This study compares Gas6 expression in plasma and visceral and subcutaneous adipose tissue in 42 adults with obesity (body mass index ≥40 kg/m²) and 32 normal-weight controls to elucidate its role in obesity and related metabolic alterations. MATERIAL AND METHODS Using a case-control design, we measured Gas6 levels in plasma via a validated sandwich enzyme-linked immunosorbent assay and in adipose tissues through quantitative polymerase chain reactio with specific probes. Medians and correlations were analyzed using Mann-Whitney and Spearman tests. A general linear model assessed the impact of covariates on the Gas6-anthropometric relationship, with statistical significance determined by P values. RESULTS Plasma Gas6 levels were significantly higher in the obese group than in controls (P=0.0006). While Gas6 mRNA expression did not significantly differ in subcutaneous adipose tissue between groups, it was notably higher in visceral than subcutaneous adipose tissue in controls (P<0.05). A significant correlation was found between plasma Gas6 levels and body mass index (P=0.001). CONCLUSIONS Gas6 plasma levels are elevated in morbid obesity, particularly in visceral adipose tissue, and are linked to altered glucose tolerance in female patients. These findings highlight the role of Gas6 in obesity-related metabolic complications and suggest avenues for further research and potential therapies.

Adipose Tissue Insulin Resistance Correlates with Disease Severity in Pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease: A Prospective Cohort Study

ObjectivesTo assess the role of adipose tissue insulin resistance (Adipo-IR) in the pathogenesis of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and to determine Adipo-IR evolution during a lifestyle intervention program. Study designIn this prospective, cohort study, children and adolescents with severe obesity were recruited between July 2020 and December 2022 at an inpatient pediatric rehabilitation center. Treatment consisted of dietary intervention and physical activity. Liver steatosis and fibrosis were evaluated using ultrasound and transient elastography with controlled attenuation parameter and liver stiffness measurement. Every 4 to 6 months, anthropometric measurements, serum biochemical analysis, ultrasound and elastography were repeated. Adipo-IR was estimated by the product of the fasting serum insulin times the fasting free fatty acid concentration and hepatic IR by the homeostatic model assessment for insulin resistance (HOMA-IR), respectively. Results56% of 200 patients with obesity had evidence of steatosis on ultrasound and 26% were diagnosed with fibrosis (≥F2). Adipo-IR increased progressively from lean controls to patients with obesity to patients with MASLD and MASLD with fibrosis. Adipo-IR was already elevated in patients with only mild steatosis (p = 0.0403). Patients with more insulin-sensitive adipose tissue exhibited lower liver fat content (p < 0.05) and serum alanine transaminase levels (p = 0.001). Adipo-IR correlated positively with visceral adipose tissue weight, waist circumference, and the visceral adipose tissue/gynoid adipose tissue ratio (p < 0.001), but not with total body fat percentage (p = 0.263). After 4 to 6 months of lifestyle management, both MASLD and Adipo-IR improved. ConclusionsOur data suggest that Adipo-IR is associated with the presence of pediatric MASLD, particularly steatosis.

Metabolic Dysfunction-Associated Steatotic Liver Disease in Severe Obesity and Concordance between Invasive (Biopsy) and Noninvasive (OWLiver®) Diagnoses

Introduction: Nonalcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is an escalating health concern linked to obesity and type 2 diabetes. Despite liver biopsy being the gold standard, its invasiveness underscores the need for noninvasive diagnostic methods. Methods: A cross-sectional study was performed to assess MASLD using the noninvasive OWLiver® serum lipidomics test in a cohort of 117 patients with severe obesity undergoing bariatric surgery, comparing outcomes with liver biopsy. Exclusions (n = 24) included insufficient data, liver disease etiology other than MASLD, corticosteroid treatment, excessive alcohol consumption, low glomerular filtration rate, and declination to participate. Comprehensive laboratory tests, demographic assessments, and liver biopsies were performed. Serum metabolites were analyzed using OWLiver®, a serum lipidomic test that discriminates between healthy liver, steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and MASH with fibrosis ≥2 by means of three algorithms run sequentially. Results: Liver biopsy revealed a MASLD prevalence of 95.7%, with MASH present in 28.2% of cases. OWLiver® demonstrated a tendency to diagnose more severe cases. Body mass index (BMI), rather than the presence of type 2 diabetes, emerged as the sole independent factor linked to the probability of concordance. Therefore, the all-population concordance of 63.2% between OWLiver® and liver biopsy notably raised to 77.1% in patients with a BMI <40 kg/m2. These findings suggest a potential correlation between lower BMI and enhanced concordance between OWLiver® and biopsy. Conclusion: This study yields valuable insights into the concordance between liver biopsy and the noninvasive serum lipidomic test, OWLiver®, in severe obesity. OWLiver® demonstrated a tendency to amplify MASLD severity, with BMI values influencing concordance. Patients with BMI <40 kg/m2 may derive optimal benefits from this noninvasive diagnostic approach.

Differing intensities of a midwife-led antenatal healthy lifestyle service on maternal and neonatal outcomes: A retrospective cohort study

IntroductionMaternal obesity and excessive gestational weight gain are associated with adverse maternal and neonatal outcomes. There is uncertainty over the most effective antenatal healthy lifestyle service, with little research determining the impact of different lifestyle intervention intensities on pregnancy outcomes. MethodThis retrospective cohort study compared pregnancy and birth outcomes in women with a body mass index of 40 or above who were offered a low intensity midwife-led antenatal healthy lifestyle service (one visit) with women who were offered an enhanced service (three visits). The primary outcome was gestational weight gain. ResultsThere were no differences between the two healthy lifestyle service intensities (N = 682) in the primary outcome of mean gestational weight gain [adjusted mean difference (aMD) -1.1 kg (95 % CI -2.3 to 0.1)]. Women offered the enhanced service had lower odds of gaining weight in excess of Institute of Medicine recommendations [adjusted odds ratio (aOR) 0.63 (95 % CI 0.40–0.98)] with this reduction mainly evident in multiparous women. Multiparous women also gained less weight per week [aMD -0.06 kg/week (95 % CI -0.11 to -0.01)]. No overall beneficial effects were seen in maternal or neonatal outcomes measured such as birth weight [aMD 25 g (95 % CI -71 to 121)], vaginal birth [aOR 0.87 (95 % CI 0.64–1.19)] or gestational diabetes mellitus [aOR 1.42 (95 % CI 0.93–2.17)]. However, multiparous women receiving the enhanced service had reduced odds of small for gestational age [aOR 0.52 (95 % CI 0.31–0.87)]. This study was however underpowered to detect differences in some outcomes with low incidences. DiscussionUncertainty remains over the best management of women with severe obesity regarding effective interventions in terms of intensity. It is suggested that further research needs to consider the different classes of obesity separately and have a particular focus on the needs of nulliparous women given the lack of effectiveness of this service among these women.