Extreme Obesity Research Articles

The hepatic lipidome and HNF4α and SHBG expression in human liver.

Low plasma levels of sex hormone-binding globulin (SHBG) are a marker for obesity, insulin resistance, non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The transcription factor HNF4α is a major determinant of hepatic SHBG expression and thereby serum SHBG levels, and mediates in part the association of low SHBG with hyperinsulinemia and hepatic steatosis. We analyzed the lipidome in human liver specimens from a cohort of patients who underwent hepatic resection as a treatment for cancer, providing insight into hepatic lipids in those without extreme obesity or the clinical diagnosis of NAFLD or non-alcoholic steatohepatitis. Both steatosis and high HOMA-IR were associated with higher levels of saturated and unsaturated FA, other than arachidonic, with the most dramatic rise in 18:1 oleate, consistent with increased stearoyl-CoA desaturase activity. Individuals with low HOMA-IR had low levels of total hepatic fatty acids, while both low and high fatty acid levels characterized the high HOMA-IR group. Both insulin resistance and high levels of hepatic fat were associated with low expression levels of HNF4α and thereby SHBG, but the expression of these genes was also low in the absence of these determinants, implying additional regulatory mechanisms that remain to be determined. The relationship of all FA studied to HNFα and SHBG mRNAs was inverse, and similar to that for total triglyceride concentrations, irrespective of chain length and saturation vs unsaturation.

Autopsy practice in patients with morbid obesity

Introduction Obesity, as defined by the World Health Organization (WHO), is a body mass index (BMI) of 30 kg/m 2 or more. Obesity itself is further categorized as class 1 - BMI of 30-34 kg/m 2 , class 2 - BMI of 35-40 kg/m 2 , and class 3 or extreme obesity is defined as a BMI greater than 40 kg/m 2 . Materials and Methods From a total of 60 autopsies, 50 were adult autopsies and 10% (n=5) complied with the WHO criteria of extreme obesity, BMI above 40 kg/m 2 . Results Three of the patients were male and two - female. BMI varied from 45 to 97 kg/m 2 , with the most obese patient weighing 320 kg. Age varied from 38 to 53 years. Gross evaluation and histological changes revealed that all of the patients had hypertension and congestive heart failure with reverse type nutmeg liver and cyanosis of the spleen and kidneys, with one of the patients having pelvic and deep vein thrombosis. Conclusion Autopsies of patients with morbid obesity represent an extreme difficulty for the pathologist based on the inadequacy of the armamentarium for such patients, extreme physical workload, and the number of direct complications of obesity that need to be observed.

Mouse models for V103I and I251L gain of function variants of the human MC4R display decreased adiposity but are not protected against a hypercaloric diet

ObjectiveThe melanocortin 4 receptor (MC4R) is a G protein-coupled receptor that plays major roles in the central control of energy balance. Loss-of-function mutations of MC4R constitute the most common monogenic cause of early-onset extreme obesity in humans, whereas gain-of-function mutations appear to be protective. In particular, two relatively frequent alleles carrying the non-synonymous coding mutations V103I or I251L are associated with lower risks of obesity and type-2 diabetes. Although V103I and I251L MC4Rs showed more efficient signalling in transfected cells, their specific effects in live animals remain unexplored. Here, we investigated whether the introduction of V103I and I251L mutations into the mouse MC4R leads to a lean phenotype and provides protection against an obesogenic diet. MethodsUsing CRISPR/Cas9, we generated two novel strains of mice carrying single-nucleotide mutations into the mouse Mc4r which are identical to those present in V103I and I251L MCR4 human alleles, and studied their phenotypic outcomes in mice fed with normal chow or a high-fat diet. In particular, we measured body weight progression, food intake and adiposity. In addition, we analysed glucose homeostasis through glucose and insulin tolerance tests. ResultsWe found that homozygous V103I females displayed shorter longitudinal length and decreased abdominal white fat, whereas homozygous I251L females were also shorter and leaner due to decreased weight in all white fat pads examined. Homozygous Mc4rV103I/V103I and Mc4rI251L/I251L mice of both sexes showed improved glucose homeostasis when challenged in a glucose tolerance test, whereas Mc4rI251L/I251L females showed improved responses to insulin. Despite being leaner and metabolically more efficient, V103I and I251L mutants fed with a hypercaloric diet increased their fasting glucose levels and adiposity similar to their wild-type littermates. ConclusionsOur results demonstrate that mice carrying V103I and I251L MC4R mutations displayed gain-of-function phenotypes that were more evident in females. However, hypermorphic MC4R mutants were as susceptible as their control littermates to the obesogenic and diabetogenic effects elicited by a long-term hypercaloric diet, highlighting the importance of healthy feeding habits even under favourable genetic conditions.

Which body weight status is associated with depression? Results from a European population study

Abstract Background A bidirectional relationship has been reported between depression and obesity. Malta, a European small state, is a highly prevalent country for obesity making this population ideal to study this relationship. The aim of this study was to identify the adiposity characteristics of a population-based depression sub-group and explore for any relationships between depression and an increase in adiposity. Methods A nationally representative health examination survey was conducted in Malta. Body mass index was measured while a validated questionnaire was used to establish the presence of depression and the sociodemographic characteristics of the participants. The study population was categorized into different sub-populations according to their adiposity status (normal, overweight, obese) and their self-reported depression. Multivariate logistic regression analyses were performed to identify independent adiposity status and socio-demographic factors associated with depression. Results The prevalence of self-reported depression was 10.44% (CI 95%: 9.52 - 11.43) with a female predominance and an overweight-obese profile. Extreme obesity (>50Kg/m2) was only present in individuals without depression. Only the overweight status (OR: 1.35 CI95%: 1.03 - 1.78 p = 0.03) was statistically linked with depression along with being female, having a low education level, being unemployed or retired and being a smoker. Conclusions The adiposity driver for the growing depression epidemic appears to be overweight rather than obesity. Stressful social determinants including unemployment, retirement, low education and being female have a role in this growing health concern. This calls for preventive action plans targeting overweight status, depression along with unfavourable sociodemographic characteristics. Key messages Overweight status was found to be linked with depression. Targeted action plans to prevent overweight and depression should be implemented with special attention to population with unfavourable sociodemographic characteristics.

The Predictors of Obesity among Urban Girls and Boys Aged 8-10 Years-A Cross-Sectional Study in North-Western Poland.

Background: Children worldwide are increasingly becoming overweight and obese and developing related health problems, including hypertension, lipid disorders, abnormal glucose tolerance, type 2 diabetes, and secondary psychological disorders. The aim of the study was to determine sociodemographic risk factors that predict an increase in BMI in children at an early school age. Material and method: The study covered 4972 children aged 8–10 years, including boys (N = 2461) and girls (N = 2511). Measurements of basic anthropometric indicators were used, such as body height, body weight, body composition, and physical fitness. The criteria developed by the International Obesity Task Force (IOTF) were adopted. Sociodemographic features were analyzed based on a diagnostic survey. IBM SPSS Statistics v.25 (Mineral Midrange SA, Warsaw, Poland) and IBM SPSS Amos software (Mineral Midrange SA, Warsaw, Poland) were used to perform descriptive statistics, the Kolmogorov-Smirnov test, Pearson′s chi-square test, Student’s t-test, and the Mann-Whitney U test. The statistical significance index was assumed to be p < 0.05, while p < 0.01 was taken as an indicator of a trend which was not completely statistically significant. Results: Both the children and their parents had mainly moderate BMI. A total of 78.7% of children were within the weight norm. Among girls, extreme obesity was two times more frequent than extreme underweight. The examined boys were significantly taller, heavier, and had a higher BMI than girls. There were significant differences between boys and girls in BMI; however, gender alone accounted for less than 1% variance. The influence of parents′ characteristics was much greater, increasing the explained variance to 10%. Body weight of mothers and fathers (p < 0.001), mother′s height (p < 0.01) and both parents′ level of education (p < 0.001) were detected as significant predictors of children’s BMI. Conclusions: The analysis of selected sociodemographic and health factors determining the BMI of the child population indicates the need for preventive action and health promotion both among children and their parents.

Relationship between extreme obesity and mortality in patients with reduced ejection fraction.

Although obesity is associated with increased mortality, epidemiologic studies in heart failure have reported lower mortality in obese patients compared with matched nonobese patients (the 'obesity paradox'). However, the relationship between survival and extreme (morbid) obesity (BMI ≥ 40) is poorly understood. We evaluate survival in low ejection fraction patients across a range of BMI categories, including extreme obesity. In a retrospective review, 12 181 consecutive patients receiving nuclear stress testing at a tertiary care center were stratified based on BMI and ejection fraction. Eight-year mortality data were collected using the social security death index. Normal ejection fraction patients (internal control, ejection fraction ≥50%) exhibited the J-shaped association between mortality and BMI that is observed in the general population. Among patients with reduced ejection fraction (<50%), survival improved as obesity increased (P < 0.0001). Those with extreme obesity had the lowest mortality (n = 1134, P < 0.05). In this cohort of reduced Ejection fraction patients, the obesity paradox was observed in all weight categories, with the highest survival of all observed in the extremely obese BMI category. This further supports hypotheses that an obesity-related physiologic phenomenon affects mortality in reduced ejection fraction patients.

Altered GH-IGF-1 Axis in Severe Obese Subjects is Reversed after Bariatric Surgery-Induced Weight Loss and Related with Low-Grade Chronic Inflammation.

Endocrine disorders are common in obesity, including altered somatotropic axis. Obesity is characterized by reduced growth hormone (GH) secretion, although the insulin-like growth factor-1 (IGF-1) values are controversial. The aim of this study was to evaluate the effect of weight loss after bariatric surgery in the GH–IGF-1 axis in extreme obesity, in order to investigate IGF-1 values and the mechanism responsible for the alteration of the GH–IGF-1 axis in obesity. We performed an interventional trial in morbidly obese patients who underwent bariatric surgery. We included 116 patients (97 women) and 41 controls (30 women). The primary endpoint was circulating GH and IGF-1 values. Circulating IGF-1 values were lower in the obese patients than in the controls. Circulating GH and IGF-1 values increased significantly over time after surgery. Post-surgery changes in IGF-1 and GH values were significantly negatively correlated with changes in C-reactive protein (CRP) and free T4 values. After adjusting for preoperative body mass index (BMI), free T4 and CRP in a multivariate model, only CRP was independently associated with IGF-1 values in the follow-up. In summary, severe obesity is characterized by a functional hyposomatotropism at central and peripheral level that is progressively reversible with weight loss, and low-grade chronic inflammation could be the principal mediator.

Conditional knockout of leptin receptor in neural stem cells leads to obesity in mice and affects neuronal differentiation in the hypothalamus early after birth

Leptin, secreted by peripheral adipocytes, binds the leptin receptor (Lepr) in the hypothalamus, thereby contributing to the regulation of satiety and body weight. Lepr is expressed in the embryonic brain as early as embryonic day 12.5. However, the function of Lepr in neural precursor cells in the brain has not been resolved. To address this issue, we crossed the Leprflox/flox mice with each of Shh-Cre mice (Shh, sonic hedgehog) and Nestin (Nes)-Cre mice. We found that deletion of Lepr specifically in nestin-expressing cells led to extreme obesity, but the conditional null of Lepr in Shh-expressing cells had no obvious phenotype. Moreover, the level of leptin-activated pSTAT3 decreased in the anterior and central subregions of the arcuate hypothalamus of Shh-Cre; Leprflox/flox mice compared with the controls. By contrast, in Nes-Cre; Leprflox/flox mice, the level of leptin-activated pSTAT3 decreased in all subregions including the anterior, central, and posterior arcuate hypothalamus as well as the dorsomedial, ventromedial, and median eminence of the hypothalamus, revealing that the extensive lack of Lepr in the differentiated neurons of the hypothalamus in the conditional null mice. Notably, conditional deletion of Lepr in nestin-expressing cells enhanced the differentiation of neural precursor cells into neurons and oligodendroglia but inhibited differentiation into astrocytes early in postnatal development of hypothalamus. Our results suggest that Lepr expression in neural precursor cells is essential for maintaining normal body weight as well as the differentiation of neural precursor cells to the neural/glial fate in the hypothalamus shortly after birth.

Incidence and Aetiology of Gallstones Formation after Laparoscopic Sleeve Gastrectomy (Retrospective Study)

Gallstones have been shown to develop in patients who experience rapid weight loss after dietary restriction and bariatric surgery . Data regarding gallstone development after Sleeve Gastrectomy, however, are limited. The aim of this study was to evaluate the incidence of gallstones formation after laparoscopic sleeve gastrectomy as a common complication to rapid weight loss during one year period after operation.40 patients had been followed up after undergoing bariatric surgery for assessment of gallstone formation and results found according to sex, age, DM, hyperlipidemia, type of surgery, relation to BMI, rate of weight loss, timing of gallstone formation. The mean age of patients was 37 . and 27 patients were females (67.5%). Half of patients came with morbid obesity (BMI from 35 to 40), and the other half with extreme morbid obesity (BMI >40). After one year of Sleeve Gastrctomy operation 8 patients developed gallstones while 32 patient were free from gallstone formation. According to sex, 5 females developed gallstones After one year of Sleeve Gastrctomy operation, while 2 males came with the same diagnosis, p= 0.27, According to age, 4 cases Less than 40 y. presented with gallstone formation After one year of Sleeve Gastrctomy operation, while 3 cases More than 40 y. came with gallstone, p=0.75. Gallstones are a common complication after rapid weight loss from laparoscopic sleeve gastrectomy. Routine prophylactic cholecystectomy is recommended for weight reduction during laparoscopic sleeve gastrectomy.

Economic Evaluation of Surgical Treatment of Obesity

IntroductionObesity surgery is the best treatment for extreme obesity, with demonstrated long-term positive outcomes. The potential cost-savings generated by the improvement of comorbidities after surgery can justify the allocation of more resources in the surgical treatment of obesity. MethodsThis was an observational, descriptive, longitudinal and retrospective study. Eligible patients underwent Roux-en-Y gastric bypass surgery at the Hospital Universitario Central de Asturias between 2003 and 2012. The established minimum follow-up period was two years. We calculated the individualized cost per patient treated (bottom-up) as well as per Diagnosis-Related Group (DRG) codes (top-down). ResultsOur study included 307 patients. The average cost per hospitalization calculated by DRG codes was €6545.90, and the average cost per patient was €10572.20. DRG 288 represented 91% of the series, with a value of €4631. The number of medications also decreased during this period, from 2.86 to 0.78 per medically treated patient, representing a cost reduction of €4433 per patient with all the obesity-related comorbidities analyzed. ConclusionsTwo years after Roux-en-Y gastric bypass conducted at Hospital Universitario Central de Asturias, the savings in drug costs for patients with multiple pathologies would compensate the inherent costs of the surgical treatment itself. Our results showed that DRG-related costs were insufficient to make a correct economic evaluation, so we recommend an individualized cost calculating method.

The Effect of Bariatric Surgery on Weight Loss and Metabolic Changes in Adults with Obesity.

Methods of treating obesity, such as changes in lifestyle, physical activity, restrictive diets, and psychotherapy, are not sufficient. Currently, it is considered that in the case of patients who meet the eligibility criteria for surgery, the treatment of choice should be bariatric surgery. The aim of this study was to assess the weight loss and metabolic changes in a group of adults with obesity undergoing bariatric surgery. The study involved 163 patients whose body mass index (BMI) exceeded 40 or 35 kg/m2, concurrent with at least one metabolic sequelae. In 120 of the cases (74%), sleeve gastrectomy was used; in 35 (21%), gastric banding was used; and in 8 (5%), laparoscopic Roux-en-Y gastric bypass was used. Metabolic parameters such as total cholesterol, LDL-cholesterol (low-density lipoprotein cholesterol), HDL-cholesterol (high-density lipoprotein cholesterol), triglycerides, and glucose were measured preoperatively and postoperatively, as well as the creatinine, creatine kinase (CK-MB), and leptin activity. In patients undergoing bariatric surgery, a significant decrease in excess weight (p < 0.001) was observed at all the analyzed time points, compared to the pre-surgery value. Weight loss after surgery was associated with a significant improvement in glycemia (109.6 ± 48.0 vs. 86.6 ± 7.9 mg/dL >24 months after surgery; p = 0.003), triglycerides (156.9 ± 79.6 vs. 112.7 ± 44.3 mg/dL >24 months after surgery; p = 0.043) and leptin (197.50 ± 257.3 vs. 75.98 ± 117.7 pg/mL 12 months after surgery; p = 0.0116) concentration. The results of the research confirm the thesis on the effectiveness of bariatric surgery in reducing excess body weight and improving metabolic parameters in patients with extreme obesity.

Differential Outcomes and Clinical Challenges of NAFLD With Extreme Obesity.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. The prevalence of extreme obesity, defined as body mass index (BMI) of 50 kg/m2 or higher, is rising more rapidly than overall obesity. We aimed to compare the clinical outcomes and performance of noninvasive fibrosis assessment tools in NAFLD with or without extreme obesity. A retrospective analysis was performed in 304 patients with NAFLD with extreme obesity and compared them to patients with NAFLD with BMI of 40 kg/m2 or less, matched for age, gender, race, and liver fibrosis stage. The mean age of the NAFLD with extreme obesity cohort was 55.9 years, BMI 55 kg/m2, and 49.7% had cirrhosis at initial evaluation. Baseline cirrhosis and coronary artery disease were associated with increased risk of death, and dyslipidemia with decreased risk of mortality. Age, insulin use, hypertension, albumin and platelet count were associated with cirrhosis. Fifteen percent of patients had weight‐loss surgery, but this was not associated with survival or risk of cirrhosis. Of the 850 abdominal ultrasound scans performed in 255 patients, 24.1% were deemed suboptimal for hepatocellular carcinoma screening. The mean NAFLD fibrosis score (NFS) in the extreme obesity cohort, versus a propensity‐matched cohort with BMI of 40 kg/m2 or less, was significantly different for both low fibrosis (F0‐F2) (0.222 vs. −1.682, P < 0.0001) and high fibrosis (F3‐F4) (2.216 vs. 0.557, P < 0.001). Conclusion: NAFLD with extreme obesity is associated with increased risk of liver‐related and overall mortality. Accurate noninvasive assessment of liver fibrosis, low rates of weight loss surgery, and high failure rate of ultrasound were identified as clinical challenges in this population.

Assessment of Kidney Function in Patients With Extreme Obesity: A Narrative Review.

To discuss the evidence and caveats associated with estimated and measured creatinine clearance (eClCr and mClCr) and glomerular filtration rate (eGFR and mGFR) assessments of kidney function in patients with more extreme forms of obesity. PubMed (1976 to mid-May 2020) was used, with bibliographies of retrieved articles searched for additional articles. Articles using gold standard mGFR to evaluate eClCr, mClCr, and eGFR assessments of kidney function in patients with more extreme forms of obesity were included. The overestimation of GFR by mClCr is well established, but mClCr is an alternative to mGFR assessments for determining medication dosing in patients with extremes of body size or muscle mass, or in patients receiving narrow therapeutic index medications when eGFR is likely to be inaccurate. The vast majority of studies comparing eGFR assessments with gold standard indicators of kidney function were attempts to validate eGFR equations for diagnosing and staging chronic kidney disease (CKD). For dosing medications in patients with stable kidney function and extreme obesity, a deindexed 4-variable Modification of Diet in Renal Disease or CKD Epidemiology Collaboration equation is an alternative to Cockcroft-Gault. Consistent use of the same equation by provider and between providers within any given setting is of paramount importance. In patients with extreme obesity and stable kidney function, eClCr or eGFR using deindexed values provides estimates of function for dosing adjustments of medications with elimination by the kidneys, but more research is needed with respect to the best size descriptor to use with estimating equations.

Testing for causality between systematically identified risk factors and glioma: a Mendelian randomization study

BackgroundWhilst epidemiological studies have provided evidence of associations between certain risk factors and glioma onset, inferring causality has proven challenging. Using Mendelian randomization (MR), we assessed whether associations of 36 reported glioma risk factors showed evidence of a causal relationship.MethodsWe performed a systematic search of MEDLINE from inception to October 2018 to identify candidate risk factors and conducted a meta-analysis of two glioma genome-wide association studies (5739 cases and 5501 controls) to form our exposure and outcome datasets. MR analyses were performed using genetic variants to proxy for candidate risk factors. We investigated whether risk factors differed by subtype diagnosis (either glioblastoma (n = 3112) or non-glioblastoma (n = 2411)). MR estimates for each risk factor were determined using multiplicative random effects inverse-variance weighting (IVW). Sensitivity analyses investigated potential pleiotropy using MR-Egger regression, the weighted median estimator, and the mode-based estimator. To increase power, trait-specific polygenic risk scores were used to test the association of a genetically predicated increase in each risk factor with glioma onset.ResultsOur systematic search identified 36 risk factors that could be proxied using genetic variants. Using MR, we found evidence that four genetically predicted traits increased risk of glioma, glioblastoma or non-glioblastoma: longer leukocyte telomere length, liability to allergic disease, increased alcohol consumption and liability to childhood extreme obesity (> 3 standard deviations from the mean). Two traits decreased risk of non-glioblastoma cancers: increased low-density lipoprotein cholesterol (LDLc) and triglyceride levels. Our findings were similar across sensitivity analyses that made allowance for pleiotropy (genetic confounding).ConclusionsOur comprehensive investigation provides evidence of a causal link between both genetically predicted leukocyte telomere length, allergic disease, alcohol consumption, childhood extreme obesity, and LDLc and triglyceride levels, and glioma. The findings from our study warrant further research to uncover mechanisms that implicate these traits in glioma onset.

1244-P: Impact of Maternal Fasting Glucose in Pregnancy on Excess Weight at Preschool Age in the Offspring

Aim: To examine the association between elevated maternal fasting plasma glucose (FPG) during pregnancy and obesity in the offspring. Methods: For women without pre-existing diabetes in 2 zones in Alberta, Canada with births between 2005 - 2013, maternal data were linked to offspring’s birth registry and preschool immunization records (w/height, weight) between 2009-2017. A 50-g glucose challenge test (GCT) followed by a 75-g OGTT was used to diagnose GDM. Pregnancies were grouped as follows: 1) GCT negative; 2) OGTT negative; 3) elevated FPG on the OGTT; and 4) elevated 1-hour and/or 2-hour OGTT only. WHO criteria were used to identify children who were overweight, obese, or extremely obese. Results: Of 79,156 pregnancies, 80.3% were GCT negative, 14.7% were OGTT negative, 1.3% had elevated FPG, and 3.7% had elevated post-load glucose only. Both LGA and pre-school obesity rates were highest in pregnancies with abnormal FPG (Figure). Relative to children of GCT negative pregnancies, children of pregnancies with elevated maternal FPG had adjusted odds ratio (aOR, 95% CI) 3.0, (2.6-3.6) for LGA; and aOR 1.3 (1.1 - 1.6) for overweight, aOR 2.4 (1.9 - 3.0) for obesity, aOR 3.5 (2.7 - 4.7) for extreme obesity at preschool age. Conclusion: The effect of elevated maternal FPG in pregnancy on offspring weight extends to early childhood. These children may be candidates for early pediatric weight and health interventions. Disclosure P. Kaul: None. A. Savu: None. L.E. Moore: None. R.O. Yeung: Research Support; Self; AstraZeneca, Novo Nordisk Inc. Speaker’s Bureau; Self; Merck &amp; Co., Inc. E.A. Ryan: None. Funding Canadian Institutes of Health Research; University Hospital Foundation

Optimization of a MALDI-Imaging protocol for studying adipose tissue-associated disorders

Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) is increasingly recognized for its potential in the discovery of novel biomarkers directly from tissue sections. However, there are no MALDI IMS studies as yet on the adipose tissue, a lipid-enriched tissue that plays a pivotal role in the development of obesity-associated disorders. Herein, we aimed at developing an optimized method for analyzing adipose tissue lipid composition under both physiological and pathological conditions by MALDI IMS. Our studies showed an exacerbated lipid delocalization from adipose tissue sections when conventional strategies were applied. However, our optimized method using conductive-tape sampling and 2,5-dihydroxybenzoic acid (DHB) as a matrix, preserved the anatomical organization and minimized lipid diffusion from sample sections. This method enabled the identification of a total of 625 down-regulated and 328 up-regulated m/z values in the adipose tissue from a rat model of extreme obesity as compared to lean animals. Combination of MALDI IMS and liquid chromatography (LC)-MS/MS data identified 44 differentially expressed lipid species between lean and obese animals, including phospholipids and sphingomyelins. Among the lipids identified, SM(d18:0_18:2), PE(P-16:0_20:0), and PC(O-16:0_16:1) showed a differential spatial distribution in the adipose tissue of lean vs. obese animals. In sum, our method provides a valuable new tool for research on adipose tissue that may pave the way for the identification of novel biomarkers of obesity and metabolic disease.

Smoking habits in HIV-infected people compared with the general population in Italy: a cross-sectional study

BackgroundTobacco use is a leading cause of preventable diseases and death for all individuals, even more so for people living with HIV (PLWH), due to their status of chronic inflammation. To date, in Italy no study was performed to compare smoking habits in PLWH and the general population. We aimed to investigate smoking habits in PLWH, as compared to the general population.MethodsMulti-center cross-sectional study. Smoking habits were compared between PLWH and the general population. PLWH were enrolled in the STOPSHIV Study. The comparison group from the general population was derived from a survey performed by the National Statistics Institute (ISTAT), with a stratified random sampling procedure matching 2:1 general population subjects with PLWH by age class, sex, and macro-area of residence.ResultsThe total sample consisted of 1087 PLWH (age 47.9 ± 10.8 years, male 73.5%) and 2218 comparable subjects from the general population. Prevalence of current smokers was 51.6% vs 25.9% (p < 0.001); quitting smoking rate was 27.1% vs. 50.1% (p < 0.001) and the mean number of cigarettes smoked per day was 15.8 vs. 11.9 (p < 0.001), respectively for PLWH and the general population. Smoking and heavy smoking rates amongst PLWH were significantly higher even in subjects who reported diabetes, hypertension and extreme obesity (p < 0.001). Logistic regressions showed that PLWH were more likely current smokers (adjusted Odds Ratio, aOR = 3.11; 95% Confidence Interval (CI) =2.62–3.71; p < 0.001) and heavy smokers (> 20 cigarettes per day) (aOR = 4.84; 95% CI = 3.74–6.27; p < 0.001). PLWH were less likely to have quitted smoking (aOR = 0.36; 95% CI = 0.29–0.46; p < 0.001).ConclusionHIV-infected patients showed a higher rate of current smokers, a larger number of cigarettes smoked and a lower quitting rate than the general population. Our findings emphasize the need for smoking cessation strategies targeting HIV persons.

Safety and Efficacy of Bariatric Surgery in Cirrhosis Patients With Extreme Obesity.

To assess the safety and efficacy of bariatric surgery in patients with cirrhosis. Bariatric surgery may be a viable option for patients with cirrhosis and extreme obesity. However, the risk of liver decompensation after surgery is not thoroughly investigated. We conducted a case-controlled study with 106 obese patients with cirrhosis (cases) and 317 age, sex, body mass index-, and type of surgery-matched obese patients without cirrhosis (controls) who underwent bariatric surgery. Patients with cirrhosis were predominantly Child-Pugh class A (97%) with the diagnosis established prior to surgery in only 46%. In the cirrhosis group, there was no death in the first 30 days compared with 1 patient in the control group. At 90 days there was 1 death in the cirrhosis group but no additional deaths in the control group. In total, 12 months after the surgery, there were 3 deaths in the cirrhosis group and 1 in the control group (2.8% vs 0.6%, P = 0.056). The surgery-related length of stay was significantly longer in patients with cirrhosis (3.7 ± 4.0 vs 2.6 ± 2.4 d, P = 0.001), but the 30-day readmission rate was lower (7.5% vs 11.9%, P = 0.001). The percent of total weight loss at 30 and 90-days was not significantly different between the groups and remained that way even at 1 year (29.1 ± 10.9 vs 31.2 ± 9.4%, P = 0.096). Bariatric surgery in obese cirrhotic patients is not associated with excessive mortality compared with noncirrhotic obese patients.

Detailed perioperative risk among patients with extreme obesity undergoing nonbariatric general surgery

BackgroundThe obesity epidemic has spread rapidly across the United States. Although overweight and obese patients have a paradoxically lower risk for postoperative morbidity and mortality, the risks associated with extreme classes of obesity (morbid obesity, super obesity, and super-super obesity) have not been described. MethodsWe queried the National Surgical Quality Improvement Program database from 2012 to 2016. Of 1,815,251 surgical cases, there were 3,946 vascular cases, 237,777 emergency procedures, and 75,177 cases with missing data that were removed. The remaining 1,378,711 cases were included in this analysis. Multivariable linear and logistic regression was performed to assess the impact of body mass index on postoperative outcomes. ResultsPatients within the super obesity and super-super obesity groups had the highest procedure-adjusted mortality risk among all body mass index classes (odds ratio = 2.31 and 2.63, respectively). Morbid obesity and underweight groups had moderate risk (odds ratio = 1.37 and 1.88, respectively), while those in the overweight and obesity class I and II cohorts had improved or equivocal mortality risk compared to normal body mass index class patients. Risk-adjusted and unadjusted multivariable models demonstrated that extreme obesity classes (morbid obesity, super obesity, and super-super obesity) have a graduated escalation of perioperative morbidity, infectious, and critical care complications. ConclusionFurther detailing extreme obesity-related risk beyond the obesity class III umbrella is necessary for accurate risk prediction, especially with the rising prevalence of elective nonbariatric surgery in this population. Preoperative risk assessment tools should consider subgroup risk adjustment to delineate true postoperative complication risk, facilitate patient education, and address modifiable risk factors before surgery.

Use of Small-Area Estimates to Describe County-Level Geographic Variation in Prevalence of Extreme Obesity Among US Adults

The prevalence of extreme obesity continues to increase among adults in the US, yet there is an absence of subnational estimates and geographic description of extreme obesity. This shortcoming prevents a thorough understanding of the geographic distribution of extreme obesity, which in turn limits the ability of public health agencies and policy makers to target areas with a known higher prevalence. To use small-area estimation to create county-level estimates of extreme obesity in the US and apply spatial methods to identify clusters of high and low prevalence. A cross-sectional analysis was conducted using multilevel regression and poststratification with data from the 2012 Behavioral Risk Factor Surveillance System and the US Census Bureau to create prevalence estimates of county-level extreme obesity (body mass index ≥40 [calculated as weight in kilograms divided by height in meters squared]). Data were included on adults (aged ≥18 years) living in the contiguous US. Analysis was performed from June 4 to December 28, 2018. Multilevel logistic regression models estimated the probability of extreme obesity based on individual-level and area-level characteristics. Census counts were multiplied by these probabilities and summed by county to create county-level prevalence estimates. Moran index values were calculated to assess spatial autocorrelation and identify spatial clusters of hot and cold spots. Estimates of moderate obesity were obtained for comparison. Overall, the weighted prevalence of extreme obesity was 4.0% (95% CI, 3.9%-4.1%) and the prevalence of moderate obesity was 23.7% (95% CI, 23.4%-23.9%). County-level prevalence of extreme obesity ranged from 1.3% (95% CI, 1.3%-1.3%) to 15.7% (95% CI, 15.3%-16.0%). The Pearson correlation coefficient comparing model-predicted estimates with direct estimates was 0.81 (P < .001). The Moran index I score was 0.35 (P < .001), indicating spatial clustering. Significant clusters of high and low prevalence were identified. Hot spots indicating clustering of high prevalence of extreme obesity in several regions, including the Mississippi Delta region and the Southeast, were identified, as well as clusters of low prevalence in the Rocky Mountain region and the Northeast. Substantial geographic variation was identified in the prevalence of extreme obesity; there was considerable county-level variation even in states generally known as having high or low prevalence of obesity. The results suggest that extreme obesity prevalence demonstrates spatial dependence and clustering and may support the need for substate analysis and benefit of disaggregation of obesity by group. Findings from this study can inform local and national policies seeking to identify populations most at risk from very high body mass index.