Extreme Obesity Research Articles

Role of simple cruroplasty in non-GERD morbid obese patients submitted to laparoscopic sleeve gastrectomy

Background: Surgical treatment for extreme obesity (body mass index [BMI] more than 50 kg/m 2) is on the rise as the prevalence of morbid obesity increases. This has led to the development of surgical techniques that help people lose enough weight while causing as little harm as possible. Objective: The purpose of the research was to determine if doing simple cruroplasty at the same time as laparoscopic sleeve gastrectomy (LSG) is safe and effective, and if so, to what degree. Patients and methods: This study was done on 60 people who were split into two groups. Group A had 30 people who had a laparoscopic sleeve gastrectomy and a cruroplasty at the same time. The thirty patients in Group B all underwent laparoscopic sleeve gastrectomy without the addition of a cruroplasty. Differences in outcomes and complication rates were examined between the two groups. Results: This study found that SG with simple cruroplasty is possible and safe, and it's a good way to treat denovo GERD in obese people who don't have symptoms of reflux. During a preoperative endoscopy and/or upper GI contrast study, small hiatal defects could be missed. So, it is always best to carefully look at the crura during surgery. Conclusion: The results of simple cruroplasty with laparoscopic sleeve gastrectomies to prevent GERD after SG are the same as those of laparoscopic sleeve gastrectomies without cruroplasty, and there are no major side effects.

Impact of gastric bypass surgery on the liver fibrosis of patients with extreme obesity and nonalcoholic fatty liver disease in 30-month follow-up.

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 40.3years; 83.3% were women. At a median follow-up of 30months (range: 24-36months), 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 thefibrosis 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.

Risk Factors, Clinical Consequences, Prevention, and Treatment of Childhood Obesity.

Obesity might adversely affect the health and well-being of children and their families. Childhood obesity has crucial implications for health, both during childhood and as they age. It is highly associated with many acute problems and is commonly present during childhood, making visits and hospital admissions polarized in this group of children. The problems that may affect these children can be medical, such as asthma, chronic inflammation, orthopedic abnormalities, liver disease, diabetes mellitus or dyslipidemia. Long-term consequences of cardiovascular risk factors, the persistence of obesity and premature mortality are common among adults who had obesity during their early lives. Additionally, they could also suffer from psychological issues, such as low self-esteem, which puts them at risk of a much more serious psychosocial problem that may lead to depression, as well as a disruption in educational achievements and social relationships. A healthy diet, physical activity, adequate sleep, and limited screen time are all preventive measures that should be implemented at the family and community levels, preferably through well-structured programs. Furthermore, pharmacological management of childhood obesity is limited and only used after non-pharmacological interventions have failed or in the late stages of obesity. However, recent guidelines advocate the early use of medical interventions. Approved pharmacotherapeutic options include orlistat, phentermine/topiramate combination and liraglutide. There are several other options approved primarily for other specific forms of obesity or for other indications, including setmelanotide, metformin, lisdexamfetamine, zonisamide and fluoxetine. Bariatric surgery is a safe and effective option in cases with extreme obesity and comorbidities considering the need for long-term monitoring and support for cases and their families post-surgery. This review aims to discuss and highlight the recent evidence regarding risk factors, clinical consequences, prevention, and treatment of childhood obesity.

Single Nucleotide Variants of the MCM6 Gene as a Risk Factor for Metabolically Unhealthy Obesity in Children

BackgroundLactose maldigestion associated with lactase non-persistence is a trigger for persistent meta-inflammation in metabolically unhealthy obesity (MUO), including arterial hypertension, atherogenic-type dyslipidemia, and insulin resistance. Aimto study the contribution of single nucleotide variants (SNV) of the gene minichromosome maintenance complex component 6 (MCM6) to the development of MUO in children. Materials and methods. 152 obese children aged 6-18 years were genotyped for the MCM6 gene (RT-PCR, Synevo, Ukraine). The main group (n=77) according to the IDEFICS 2014 recommendations was represented by children with MUO. The control group (n=75) consolidated of children with metabolically obesity (MHO). Additionally, whole genome sequencing (NGS, CeGat, Germany) was performed in 27 children of the main and 15 children of the control group. Verification of results: odds ratio (OR) estimate, 95% confidence interval (CI), calculation of Spearman's correlation coefficient (r) and p-value for each variable. ResultsAmong obese children, 11 MCM6 SNVs were identified (rs61752701, rs141448886, rs201537325, rs2289049, rs3087353, rs1057031, rs143348934, rs3087348, rs4988270, rs2070068). The frequency of MUO (r=0.22; p=0.020) and extreme obesity (r=0.22; p=0.022) was higher in children with with the "wild" genotype MCM6-13910 and was respectively OR 80.0; 95% CI 66.96 - 88.76 and OR 54.0%; 95% CI 40.4 - 67.03, compared with with carriers of mutant genotypes (r=-0,37; р<0,001). OR at MUO to detect SNV MCM6 G/A rs105703 - 2.6 95% СI 0.65-10. ConclusionsThe greatest contribution to the development of MUO in children is made by the G/A rs1057031 genotype out of 11 SNV MCM6 diagnosed by us.

Aberrant expression of agouti signaling protein (ASIP) as a cause of monogenic severe childhood obesity

Here we report a heterozygous tandem duplication at the ASIP (agouti signaling protein) gene locus causing ubiquitous, ectopic ASIP expression in a female patient with extreme childhood obesity. The mutation places ASIP under control of the ubiquitously active itchy E3 ubiquitin protein ligase promoter, driving the generation of ASIP in patient-derived native and induced pluripotent stem cells for all germ layers and hypothalamic-like neurons. The patient’s phenotype of early-onset obesity, overgrowth, red hair and hyperinsulinemia is concordant with that of mutant mice ubiquitously expressing the homolog nonagouti. ASIP represses melanocyte-stimulating hormone-mediated activation as a melanocortin receptor antagonist, which might affect eating behavior, energy expenditure, adipocyte differentiation and pigmentation, as observed in the index patient. As the type of mutation escapes standard genetic screening algorithms, we rescreened the Leipzig Childhood Obesity cohort of 1,745 patients and identified four additional patients with the identical mutation, ectopic ASIP expression and a similar phenotype. Taken together, our data indicate that ubiquitous ectopic ASIP expression is likely a monogenic cause of human obesity.

The Effect of Bariatric Surgery on Circulating Levels of Monocyte Chemoattractant Protein-1: A Systematic Review and Meta-Analysis.

Background: MCP-1 (monocyte chemoattractant protein) plays an important role in early phases of atherogenesis as well as in plaque destabilization, which causes cardiovascular events to play an important role in low-grade inflammation. Obesity, particularly extreme obesity, is a pivotal risk factor for atherosclerosis and many other diseases. In the early stages, bariatric surgery might stop or slow atherogenesis by suppressing inflammation, but also in later stages, preventing plaque destabilization. The aim of this meta-analysis was to provide an answer as to whether bariatric surgery has a significant effect on circulating MCP-1 level or not. Methods: A systematic literature search in PubMed, Scopus, Embase, and Web of Science was performed from inception to 1 January 2022. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. In order to heterogeneity compensation of studies in terms of study design and treatment duration, the characteristics of the studied populations random-effects model and the generic inverse variance weighting method were used. To investigate the relationship with the estimated effect size, a random-effect meta-regression model was used. To assess the exitance of publication bias in the meta-analysis, the funnel plot, Begg's rank correlation, and Egger's weighted regression tests were used. Results: Meta-analysis of 25 studies with 927 subjects included demonstrated a significant decrease of MCP-1 concentration after bariatric surgery. The data of meta-regression did not indicate any association between the alterations in body mass index (BMI) and absolute difference in MCP-1 levels, but a linear relationship between the changes in MCP-1 and length of follow-up was proven. Conclusions: Bariatric surgery significantly decreases MCP-1 concentration, but there was no association between the changes in BMI and absolute difference in MCP-1 levels before and after the surgery.

Effect of Body Mass Index on Paddle Lead Spinal Cord Stimulator Safety Implantation for Chronic Pain Management

ObjectiveSpinal cord stimulators (SCS) represent an effective treatment for patients with chronic pain issues. This study examines extremely obese patients (body mass index [BMI] ≥40) as appropriate surgical candidates for paddle lead SCS trial via partial thoracic laminectomy and whether obesity impacts implantation safety. MethodsA retrospective review of patients treated with partial thoracic laminectomy and paddle lead SCS trial between October 1, 2016 and September 30, 2019 was performed. The primary outcome was implantation safety (complication rate within minimum of 90 days) in patients with extreme obesity (BMI ≥40) compared with patients with BMI <40 and secondary outcome was effectiveness (successful trial leading to final implantation). Seventy-three patients underwent SCS trial. ResultsFour (5.48%) patients developed complications with only 1 patient in the BMI ≥40 cohort (not statistically significant). Overall trial success rate was 82.2% (60/73) with statistically significant higher success rates among patients with a BMI ≥40 (93.3% vs. 74.4%, P = 0.0183). ConclusionsWe conclude that paddle lead SCS trial in extremely obese patients is reasonable to offer with the expectation of similar safety concerns as those for patients with a lower BMI.

COMMUTE: Communication-efficient transfer learning for multi-site risk prediction

Objectives:We propose a communication-efficient transfer learning approach (COMMUTE) that effectively incorporates multi-site healthcare data for training a risk prediction model in a target population of interest, accounting for challenges including population heterogeneity and data sharing constraints across sites. Methods:We first train population-specific source models locally within each site. Using data from a given target population, COMMUTE learns a calibration term for each source model, which adjusts for potential data heterogeneity through flexible distance-based regularizations. In a centralized setting where multi-site data can be directly pooled, all data are combined to train the target model after calibration. When individual-level data are not shareable in some sites, COMMUTE requests only the locally trained models from these sites, with which, COMMUTE generates heterogeneity-adjusted synthetic data for training the target model. We evaluate COMMUTE via extensive simulation studies and an application to multi-site data from the electronic Medical Records and Genomics (eMERGE) Network to predict extreme obesity. Results:Simulation studies show that COMMUTE outperforms methods without adjusting for population heterogeneity and methods trained in a single population over a broad spectrum of settings. Using eMERGE data, COMMUTE achieves an area under the receiver operating characteristic curve (AUC) around 0.80, which outperforms other benchmark methods with AUC ranging from 0.51 to 0.70. Conclusion:COMMUTE improves the risk prediction in a target population with limited samples and safeguards against negative transfer when some source populations are highly different from the target. In a federated setting, it is highly communication efficient as it only requires each site to share model parameter estimates once, and no iterative communication or higher-order terms are needed.

Extreme Food Insecurity and Malnutrition in Haiti: Findings from a Population-Based Cohort in Port-au-Prince, Haiti.

Haiti is one of the most food-insecure (FIS) nations in the world, with increasing rates of overweight and obesity. This study aimed to characterize FIS among households in urban Haiti and assess the relationship between FIS and body mass index (BMI) using enrollment data from the Haiti Cardiovascular Disease Cohort Study. FIS was characterized as no/low, moderate/high, and extreme based on the Household Food Security Scale. Multinomial logistic generalized estimating equations were used to evaluate the association between FIS categories and BMI, with obesity defined as BMI ≥ 30 kg/m2. Among 2972 participants, the prevalence of moderate/high FIS was 40.1% and extreme FIS was 43.7%. Those with extreme FIS had higher median age (41 vs. 38 years) and were less educated (secondary education: 11.6% vs. 20.3%) compared to those with no/low FIS. Although all FIS categories had high obesity prevalence, those with extreme FIS compared to no/low FIS (15.3% vs. 21.6%) had the lowest prevalence. Multivariable models showed an inverse relationship between FIS and obesity: moderate/high FIS (OR: 0.77, 95% CI: 0.56, 1.08) and extreme FIS (OR: 0.58, 95% CI: 0.42, 0.81) versus no/low FIS were associated with lower adjusted odds of obesity. We found high prevalence of extreme FIS in urban Haiti in a transitioning nutrition setting. The inverse relationship between extreme FIS and obesity needs to be further studied to reduce both FIS and obesity in this population.

Body mass index during maintenance therapy and relapse risk in children with acute lymphoblastic leukemia: AChildren's Oncology Group report.

Obesity at diagnosis of childhood acute lymphoblastic leukemia (ALL) is associated with greater risk of relapse; whether this association extends to obesity during maintenance is unstudied. This study used data from AALL03N1 to calculate median body mass index (BMI) for 676 children over 6 consecutive months during maintenance therapy; BMI percentile (BMI%ile) were operationalized as normal/underweight (<85%ile), overweight/obese (85%-98%ile), and extreme obesity (≥99%ile). Hazard of relapse was estimated using multivariable proportional subdistributional hazards regression after adjusting for all relevant demographic and clinical predictors. Median age at study enrollment was 6 years and median length of follow-up was 7.9years. Overall, 43.3% of the cohort was underweight/normal weight, 44.8% was overweight/obese, and 11.8% had extreme obesity. Cumulative incidence of relapse at 4 years from study enrollment was higher among those with extreme obesity (13.6%±4.5%) compared to those with underweight/normal weight (9.0%±2.1%). Multivariable analysis revealed that children with extreme obesity had a 2.4-fold (95% confidence interval [CI], 1.1-5.0; p=.01) greater hazard of relapse compared to those who were underweight/normal weight. Overweight/obese patients were at comparable risk to those who were underweight/normal weight (hazard ratio, 0.8; 95% CI, 0.4-1.6). Erythrocyte thioguanine nucleotide (TGN) levels were significantly lower among children with extreme obesity compared to those with underweight/normal weight (141.6 vs. 168.8 pmol/8×108 erythrocytes; p=.0002), however, the difference in TGN levels did not explain the greater hazard of relapse among those with extreme obesity. Extreme obesity during maintenance therapy is associated with greater hazard of relapse in children with ALL. Underlying mechanisms of this association needs further investigation. Findings from this study demonstrate that extreme obesity during maintenance therapy is associated with a greater hazard of relapse among children with acute lymphoblastic leukemia. We show that children with obesity have lower levels of erythrocyte thioguanine nucleotides even after adjusting for adherence to oral chemotherapy. However, these lower levels do not explain the greater hazard of relapse, paving the way for future studies to explore this association.

Extreme obesity is a strong predictor for in-hospital mortality and the prevalence of long-COVID in severe COVID-19 patients with acute respiratory distress syndrome

Acute Respiratory Distress Syndrome (ARDS) is common in COVID-19 patients and is associated with high mortality. The aim of this observational study was to describe patients’ characteristics and outcome, identifying potential risk factors for in-hospital mortality and for developing Long-COVID symptoms. This retrospective study included all patients with COVID-19 associated ARDS (cARDS) in the period from March 2020 to March 2021 who were invasively ventilated at the intensive care unit (ICU) of the University Hospital Dresden, Germany. Between October 2021 and December 2021 patients discharged alive (at minimum 6 months after hospital discharge—midterm survival) were contacted and interviewed about persistent symptoms possibly associated with COVID-19 as well as the quality of their lives using the EQ-5D-5L-questionnaire. Long-COVID was defined as the occurrence of one of the symptoms at least 6 months after discharge. Risk factors for mortality were assessed with Cox regression models and risk factors for developing Long-COVID symptoms by using relative risk (RR) regression. 184 Patients were included in this study (male: n = 134 (73%), median age 67 (range 25–92). All patients were diagnosed with ARDS according to the Berlin Definition. 89% of patients (n = 164) had severe ARDS (Horovitz-index < 100 mmHg). In 27% (n = 49) extracorporeal membrane oxygenation was necessary to maintain gas exchange. The median length of in-hospital stay was 19 days (range 1–60). ICU mortality was 51%, hospital mortality 59%. Midterm survival (median 11 months) was 83% (n = 55) and 78% (n = 43) of these patients presented Long-COVID symptoms with fatigue as the most common symptom (70%). Extreme obesity (BMI > 40 kg/m2) was the strongest predictor for in-hospital mortality (hazard ratio: 3.147, confidence interval 1.000–9.897) and for developing Long-COVID symptoms (RR 1.61, confidence interval 1.26–2.06). In-hospital mortality in severe cARDS patients was high, but > 80% of patients discharged alive survived the midterm observation period. Nonetheless, most patients developed Long-COVID symptoms. Extreme obesity with BMI > 40 kg/m2 was identified as independent risk factor for in-hospital mortality and for developing Long-COVID symptoms.Trial registration DRKS-ID DRKS00027856.

PSUN114 Correlation of Percent Body Fat From Two-Electrode Bioelectric Impedance Analysis and Dual-Energy X-Ray Absorptiometry

Abstract Background The diagnosis of obesity by measuring body mass index (BMI) is limited in some populations. Moreover, BMI does not reflect body fat levels, which are the main factors causing metabolic-related disorders, including cardiovascular disease. There are various methods for measuring percent body fat, such as using a two-electrode bioelectric impedance analysis (BIA), which is considered a portable and easy-to-use tool. In Thailand, the studies on BIA compared to standard method, dual-energy X-ray absorptiometry (DEXA scan) are still limited. Objective To study a correlation of percent body fat from two-electrode BIA and DEXA scan Methods: In this cross-sectional study, percent body fat were measured using three of two-electrode BIA and DEXA scan within the same week. The subjects were categorized into 3 groups according to their BMI: normal group (18.5 - 22.9 kg/m2), overweight and obese group (23 - 29.9 kg/m2) and extreme obesity group (≥ 30 kg/m2). Results A total of 30 study participants, with an average age of 28.07 ± 5.81 years, correlation of percent body fat as measured two-electrode BIA and DEXA scan were Omron®HBF-222T = 0.801, Tanita®BC-730 = 0.922, and Xiaomi®Body Composition Scale 2 = 0.884. All three correlations were strong (r 3 0.75) and statistically significant (p-value &amp;lt;0.001). Moreover, the percent body fat measured by three of two-electrode BIA were no different (p-value = 0.167). Conclusion The percent body fat measured by three of two-electrode BIA and DEXA scan is highly correlated and not statistically difference between three brands. Therefore, two-electrode BIA can be used as alternative method to DEXA scan to measure percent body fat. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Extreme obesity in the ICU

Morbid obesity remains an extremely serious disorder resulting in significant impairment of health all over the World. This is particularly true especially now in the setting of lockdowns and people not exercising due to the recent COVID-19 pandemic. In general, overweight and obese adults are at in increased risk of morbidity and mortality from many acute and chronic medical conditions, including hypertension, dyslipidemia, coronary heart disease, diabetes mellitus, gallbladder disease, respiratory disease, some types of cancer, gout and arthritis. Although body weight that exceeds ideal standards as determined by age, sex and height may be accounted for by a greater muscle mass or bone mass, the majority of individuals who weigh more than 20% over their calculated ideal body weight (IBW) have excessive adipose mass. What is even more alarming is the fact that the incidence of obesity in the USA has increased progressively since 1960, when the first survey was conducted. More recent data has demonstrated that the prevalence of obesity is three times higher in the USA than France, and one-and-a-half times that of England. As obesity is such a pervasive disorder in our society, and because obesity is an important risk factor for many diseases, it is not surprising that many obese patients are treated in the intensive care unit (ICU).

Dilemmas Related to Direct-Acting Oral Anticoagulant Administration in Patients With Extreme Obesity.

The objective of the study was to discuss the controversies surrounding the use and dosing of direct-acting oral anticoagulants (DOACs) in obese patients recognizing the limitations of the existing evidence base that preclude strong recommendations. A literature search of MEDLINE was performed (2020 to end August 2022) subsequent to recent guidelines using the following search terms: direct acting anticoagulants, obesity, rivaroxaban, apixaban, edoxaban, dabigatran, dabigatran etexilate, and clinical practice guidelines. English-language studies and those conducted in adults were selected. The available randomized studies evaluating DOACs had relatively small numbers of patients with more extreme forms of obesity (body mass index [BMI] > 40 kg/m2) and none of the larger studies had a specific focus on dosing DOACs in obese patients. Recent guidelines by the International Society on Thrombosis and Haemostasis (ISTH) have specific recommendations for dosing DOACs in obesity. There are pharmacokinetic/pharmacodynamic and observational studies published before and after the ISTH guidelines with a focus on DOAC dosing in obese patients that generally support the recommendations in the guidelines, but most involved small numbers of patients usually with BMIs <45 kg/m2. This review discusses DOAC dosing in obesity with important considerations for clinicians related to DOAC choice and dosing. Dosing alterations of DOACs do not appear to be necessary when used for either prophylaxis or treatment in patients with BMIs up to approximately 45 to 50 kg/m2, but research is needed for BMIs >50 kg/m2.

Effect of Bariatric Surgery on Intima Media Thickness: A Systematic Review and Meta-Analysis

Background: Obesity, and in particular extreme obesity, as a global health problem is an important risk factor for many diseases, including atherosclerotic cardiovascular disease (ACVD). Bariatric surgery might stop or slow atherogenesis by decreasing excessive weight in the early stages of atherogenesis, by suppressing low-grade systemic inflammation as well as by inhibiting oxidative stress and endothelial dysfunction. The aim of this meta-analysis was to provide an answer to whether bariatric surgery has a significant effect on intima-media thickness (IMT) which is a surrogate marker of early atherosclerosis and has a good correlation with atherosclerotic coronary heart disease. Methods: A systematic literature search in PubMed, Scopus, Embase, and Web of Science as well as grey literature was performed from inception to 1 July 2022. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V3 software. Overall, the estimate of effect size was measured by a random effects meta-analysis. To account for the heterogeneity of studies regarding study design, characteristics of the populations, and treatment duration, a random-effects model (using the DerSimonian–Laird method) and the generic inverse variance weighting approach were used. To assess the existence of publication bias in the meta-analysis, the funnel plot, Begg’s rank correlation, and Egger’s weighted regression tests were used. Results: The meta-analysis of 30 trials, including 1488 subjects, demonstrated a significant decrease in IMT after bariatric surgery. The reduction in IMT was also robust in the leave-one-out sensitivity analysis. It must be stressed that the results of the random-effects meta-regression did not suggest any relationship between the changes in IMT and delta body mass index (BMI) or duration of follow-up after the bariatric surgery. However, the subgroup analyses showed a better IMT reduction after laparoscopic sleeve gastrectomy (LSG) when compared to Roux-en-Y gastric bypass (RYGB). Within a year, the IMT follow-up values showed a further improvement. Conclusions: Bariatric surgery significantly reduced IMT. Significant associations were found between the surgery type and IMT changes, as well as a significant effect of follow-up duration on the changes of IMT after bariatric surgery.

Chondroprotection of leptin deficiency demystified?

Using the unique preclinical model of lipodystrophy—a rare heterogeneous disorder characterized by the absence of subcutaneous adipose tissue—paracrine signaling from fat, rather than body weight, has been identified as a mediator of spontaneous and injury-induced joint degeneration1. Lipodystrophy is a leptin-deficient state that can be considered a lipid-partitioning disorder associated with severe insulin resistance, fatty liver, and hyperlipidemia (www.endotext.org). Other leptin-deficient states associated with extreme obesity are also chondroprotective, including deficiency due to a leptin gene mutation, as observed in ob/ob mice2, functional deficiency due to a leptin receptor gene mutation or silencing, as observed in db/db mice2, and lentiviral vector-mediated leptin receptor targeting3.

Whole-Exome Sequencing identified Olfactory Receptor genes as a key contributor to extreme obesity with progression to nonalcoholic steatohepatitis in Mexican patients: Olfactory receptor genes in obese NASH patients

Obesity is a global health problem that triggers fat liver accumulation. The prevalence of obesity and the risk of non-alcoholic steatohepatitis (NASH) among young obese Mexican is high. Furthermore, genetic predisposition is a key factor in weight gain and disrupts metabolism. Herein, we used Whole-Exome Sequencing to identify potential causal variants and the biological processes that lead to obesity with progression to NASH among Mexican patients. Whole-Exome Sequencing was performed in nine obese patients with NASH diagnosis with a BMI ≥30 kg/m2 and one control (BMI=24.2 kg/m2) by using the Ion S5TM platform. Genetic variants were determined by Ion Reporter software. Enriched GO biological set genes were identified by the WebGestalt tool. Genetic variants within ≥2 obese NASH patients and having scores of SIFT 0.0-0.05 and Polyphen 0.85-1.0 were categorized as pathogenic. A total of 1359 variants with a probable pathogenic effect were determined in obese patients with NASH diagnosis. After several filtering steps, the most frequent pathogenic variants found were rs25640-HSD17B4, rs8105737-OR1I1, rs998544-OR5R1, and rs4916685, rs10037067, and rs2366926 in ADGRV1. Notably, the primary biological processes affected by these pathogenic variants were the sensory perception and detection of chemical stimulus pathways in which the olfactory receptor gene family was the most enriched. Variants in the olfactory receptor genes were highly enriched in Mexican obese patients that progress to NASH and could be potential targets of association studies.

Extreme obesity and leptin receptor deficiency. A case report

Leptin is vital for maintaining energy homeostasis, by controlling food intake and regulating energy expenditure (fatty acids). It also participates in glycemic homeostasis, thyroid activity, and reproductive and immune functions. Leptin resistance is a phenomenon that appears gradually and does not simultaneously affect all organs and tissues equally. In models of obesity induced by a high-fat diet, leptin resistance initially manifests in the hypothalamus. This type of central resistance can justify an alteration in eating patterns (hyperphagia) and a decrease in sympathetic tone, which can contribute to the increase in fat deposits in adipose tissue

Visceral Adipose Tissue E2F1-miRNA206/210 Pathway Associates with Type 2 Diabetes in Humans with Extreme Obesity.

Objective: Up-regulated expression of transcription-factor E2F1 in human visceral adipose tissue (VAT) characterizes a dysmetabolic obesity sub-phenotype. An E2F1-miRNA network has been described in multiple cancers. Here we investigated whether elevated VAT-E2F1 in obesity is associated with VAT-miRNA alterations similar to, or distinct from, those described in cancer. Furthermore, we assessed if E2F1-associated miRNA changes may contribute to the link between high- VAT-E2F1 and a dysmetabolic obesity phenotype. Methods: We assembled a cohort of patients with obesity and high-VAT-E2F1, matched by age, sex, ±BMI to patients with low-VAT-E2F1, with and without obesity (8 patients/groupX3 groups). We performed Nanostring©-based miRNA profiling of VAT samples from all 24 patients. Candidate E2F1-related miRNAs were validated by qPCR in an independent cohort of patients with extreme obesity, with or without type-2-diabetes (T2DM) (n = 20). Bioinformatic tools and manipulation of E2F1 expression in cells were used to establish the plausibility of the functional VAT-E2F1-miRNA network in obesity. Results: Among n = 798 identified miRNAs, 17 were differentially expressed in relation to E2F1 and not to obesity itself. No evidence for the cancer-related E2F1-miRNA network was identified in human VAT in obesity. In HEK293-cells, overexpression/downregulation of E2F1 correspondingly altered the expression of miRNA-206 and miRNA-210-5p, two miRNAs with reported metabolic functions consistent with those of E2F1. In VAT from both cohorts, the expression of both miRNA-206 and 210-5p intercorrelated, and correlated with the expression of E2F1. In cohort 1 we did not detect significant associations with biochemical parameters. In cohort 2 of patients with extreme obesity, all those with high VAT-E2F1 showed a diabetes-complicated obesity phenotype and higher expression of miRNA-206 and miRNA-210-5p, which also correlated with fasting glucose levels (both miRNAs) and fasting insulin (miRNA-210-5p). Conclusions: Whilst the previously described cancer-related E2F1-miRNA network does not appear to operate in VAT in obesity, miRNAs-206 and 210-5p may link high-E2F1 expression in VAT with diabetes-complicated extreme obesity phenotype.

Improving health services for patients with extreme obesity requiring bariatric level care at Wellington Regional Hospital: a clinical audit.

To benchmark the quality of bariatric service delivery against moving and handling and patient care best practice standards, and determine the prevalence of hospitalised patients admitted to Wellington Regional Hospital requiring bariatric level care. A clinical audit consisting of retrospective case-note review and cross-sectional survey was conducted and benchmarked against Accident Compensation Corporation (ACC) national standards. Information recorded included patient demographics, admission planning, patient anthropometric and risk assessments, provider communication, room preparation, mobilisation plan, equipment needs, space and facility design considerations, discharge planning and reportable events. A total of 574 patients were included. The prevalence of hospitalised patients requiring bariatric services was 6.4%. One third of patients (34.3%) were not identified by clinical teams as requiring bariatric support. Most bed (80%) and bathroom (83%) spaces failed to achieve the facility design standard. The majority of patient focused moving and handling hazards were documented whereas environmental hazards or equipment limitations were poorly reported. Only 26.1% of patients had a documented discharge plan. Inadequate identification of patients requiring bariatric support and insufficient documentation of bariatric service delivery were identified. Improving policy adherence will address shortcomings in the provision of a safe environment and high quality care for bariatric patients.