Long-term adverse events after sleeve gastrectomy or gastric bypass: a 7-year nationwide, observational, population-based, cohort study.

BACKGROUND: Concerns are rising about the late adverse events following gastric bypass and sleeve gastrectomy. We aimed to assess, over a 7-year period, the late adverse events after gastric bypass and sleeve gastrectomy compared with matched control groups. METHODS: In this nationwide, observational, population-based, cohort study, we used data extracted from the French National Health Insurance (Système National des Données de Santé) database. All patients undergoing gastric bypass or sleeve gastrectomy in France in 2009, except those who had undergone bariatric surgery in the previous 4 years before inclusion, were matched with control patients with obesity in terms of age, sex, BMI category, baseline antidiabetic therapy, and baseline insulin therapy. Exclusion criteria for the control group included cancer, pregnancy, chronic infectious disease, serious acute or chronic disease in 2008-09, or previous (2005-09) or forthcoming (2010-11) bariatric surgery. The incidence rate was calculated for each type of adverse event leading to inpatient hospital admission over a 7-year period; incidence rate ratios (with 95% CIs) were computed to compare the rate of complications among the bariatric surgery and control groups. Risks of complications during follow-up were compared using Cox proportional-hazards regression analyses. Data were analysed according to the intention-to-treat methodology. FINDINGS: From Jan 1, 2009, to Dec 31, 2009, 8966 patients who underwent bariatric surgery (7359 [82%] women; mean age 40·4 years [SD 11·3]) and 8966 matched controls (7359 [82%] women; mean age 40·9 years [11·4]) were included in analyses 4955 (55%) off 8966 patients in the bariatric surgery group had a primary gastric bypass and 4011 (45%) patients had sleeve gastrectomy. With a mean follow-up of 6·8 years (SD 0·2), mortality was lower in the gastric bypass group than in its control group (hazard ratio 0·64 [95% CI 0·52-0·78]; p<0·0001) and in the sleeve gastrectomy group than in its control group (0·38 [0·29-0·50]; p<0·0001). The gastric bypass and sleeve gastrectomy groups had higher risk than did their control groups for invasive gastrointestinal surgery or endoscopy (incidence rate ratio 2·4 [95% CI 2·1-2·7], p<0·0001, for gastric bypass vs control and 1·5 [1·3-1·7], p<0·0001, for sleeve gastrectomy vs control); for gastrointestinal disorders not leading to invasive procedures (1·9 [1·7-2·1]), p<0·0001, for gastric bypass vs control and 1·2 [1·1-1·4], p<0·0001, for sleeve gastrectomy vs control); and for nutritional disorders (4·9 [3·8-6·4], p<0·0001, for gastric bypass vs control and 1·8 [1·3-2·5], p<0·0001, for sleeve gastrectomy vs control). For psychiatric disorders, there was no significant association (1·1 [0·9-1·4], p=0·190, for gastric bypass vs control and 1·1 [0·8-1·3], p=0·645, for sleeve gastrectomy vs control), except for gastric bypass and alcohol dependence (1·8 [1·1-2·8], p=0·0124). INTERPRETATION: Despite lower 7-year mortality, patients undergoing gastric bypass or sleeve gastrectomy had higher risk of hospital admission at least once for late adverse events, except for psychiatric disorders, than did control patients, with a higher risk observed after gastric bypass than with sleeve gastrectomy. FUNDING: None.

[Monitoring adherence after weight loss surgery: Identifying factors leading to non-adherence in a cohort of 207 severely obese patients who have undergone surgery. An evaluation of severely obese patients' adherence following weight loss surgery.] / Adhésion au suivi après chirurgie bariatrique : identification des facteurs de non observance dans une cohorte de 207 patients obèses sévères opérés. Évaluation de l'adhésion du patient obèse sévère au suivi post chirurgie bariatrique.

Obese patients are increasingly being offered weight loss surgery, the success of which depends in part on the quality of a long-term follow-up after the procedure. A study was conducted with a cohort of 207 patients operated on in 2007 and 2008 who received follow-up care in a specialized nutrition department, with the aim of identifying factors affecting their adherence to their post-operative care agenda. Factors strongly linked to a lower level of adherence were the type of surgery and a patient's place of residence. These results enable us to discuss the importance of using care coordination to optimize post-operative monitoring.

Association Between Bariatric Surgery and Rates of Continuation, Discontinuation, or Initiation of Antidiabetes Treatment 6 Years Later.

Importance: Few large-scale long-term prospective cohort studies have assessed changes in antidiabetes treatment after bariatric surgery. Objective: To describe the association between bariatric surgery and rates of continuation, discontinuation, or initiation of antidiabetes treatment 6 years after bariatric surgery compared with a matched control obese group. Design, Setting, and Participants: This nationwide observational population-based cohort study extracted health care reimbursement data from the French national health insurance database from January 1, 2008, to December 31, 2015. All patients undergoing primary bariatric surgery in France between January 1 and December 31, 2009, were matched on age, sex, body mass index category, and antidiabetes treatment with control patients hospitalized for obesity in 2009 with no bariatric surgery between 2005 and 2015. Exposures: Bariatric surgery, including adjustable gastric banding (AGB), gastric bypass (GBP), and sleeve gastrectomy (SG). Main Outcome and Measure: Reimbursement for antidiabetes drugs. Mixed-effects logistic regression models estimated factors of discontinuation or initiation of antidiabetes treatment over a period of 6 years. Results: In 2009, a total of 15 650 patients (mean [SD] age, 38.9 [11.2] years; 84.6% female; 1633 receiving antidiabetes treatment) underwent primary bariatric surgery, with 48.5% undergoing AGB, 27.7% undergoing GBP, and 22.0% undergoing SG. Among patients receiving antidiabetes treatment at baseline, the antidiabetes treatment discontinuation rate was higher 6 years after bariatric surgery than in controls (-49.9% vs -9.0%, P < .001). In multivariable analysis, the main predictive factors for discontinuation were the following: GBP (odds ratio [OR], 16.7; 95% CI, 13.0-21.4), SG (OR, 7.30; 95% CI, 5.50-9.50), and AGB (OR, 4.30; 95% CI, 3.30-5.60) compared with no bariatric surgery, as well as insulin use (OR, 0.17; 95% CI, 0.13-0.22), dual therapy without insulin (OR, 0.38; 95% CI, 0.32-0.45) vs monotherapy, lipid-lowering treatment (OR, 0.76; 95% CI, 0.63-0.91), antidepressant treatment (OR, 0.67; 95% CI, 0.55-0.81), and age (OR, 0.96; 95% CI, 0.95-0.97) per year. For patients without antidiabetes treatment at baseline, the 6-year antidiabetes treatment initiation rate was much lower after bariatric surgery than in controls (1.4% vs 12.0%, P < .001). In multivariable analysis, protective factors were GBP (OR, 0.06; 95% CI, 0.04-0.09), SG (OR, 0.08; 95% CI, 0.06-0.11), and AGB (OR, 0.16; 95% CI, 0.14-0.20) vs controls, and risk factors were as follows: body mass index category (OR, 2.04; 95% CI, 1.68-2.47 for ≥50.0 vs 30.0-39.9 and OR, 1.68; 95% CI, 1.49-1.90 for 40.0-49.9 vs 30.0-39.9), antihypertensive treatment (OR, 1.49; 95% CI, 1.33-1.67), low income (OR, 1.43; 95 % CI, 1.26-1.62), and age (OR, 1.04; 95 % CI, 1.03-1.05) per year. Conclusions and Relevance: Bariatric surgery was associated with a significantly higher 6-year postoperative antidiabetes treatment discontinuation rate compared with baseline and with an obese control group without bariatric surgery.

To What Extent Does Posthospital Discharge Chemoprophylaxis Prevent Venous Thromboembolism After Bariatric Surgery?: Results From a Nationwide Cohort of More Than 110,000 Patients.

OBJECTIVE: The aim of the present study was to assess the incidence, risk factors, and the impact of posthospital discharge (PHD) chemoprophylaxis on venous thromboembolism (VTE) in patients undergoing bariatric surgery (BS). BACKGROUND: VTE is a major concern after BS, especially during the PHD period. No large-scale study has previously focused on the clinical value of PHD chemoprophylaxis. METHODS: In this nationwide observational population-based cohort study, all data from patients undergoing BS were extracted from the French National Health Insurance database (SNIIRAM) from 1st January 2012 to 31st September 2014. Logistic regression models were used to compute odds ratios for potential risk factors for VTE occurring within 90 postoperative days (PODs). The association between use of PHD chemoprophylaxis (heparin) and VTE was also assessed. RESULTS: The majority (56%) of the 110,824 patients had sleeve gastrectomy. VTE rates during the first 30 and 90 PODs were 0.34% and 0.51%, respectively. On multivariate analyses, the major risk factors for VTE during the first 90 PODs were history of VTE [odds ratio = 6.33 95% confidence interval (4.44-9.00)], postoperative complications [9.23 (7.30-11.70)], heart failure [2.45 (1.48-4.06)], and open surgery [2.38 (1.59-3.45)]. PHD chemoprophylaxis was delivered to 75% of patients. No use of PHD chemoprophylaxis [1.27 (1.01-1.61)] was an independent predictive factor of VTE during the first 90 PODs [in the gastric bypass group: 1.51 (1.01-2.29)). CONCLUSIONS: In the modern era of BS, this nationwide study shows a non-negligible rate of VTE especially after sleeve gastrectomy, depending on the individual risk level. Use of PHD chemoprophylaxis may decrease the risk of PHD VTE.

Do sleeve gastrectomy and gastric bypass influence treatment with proton pump inhibitors 4 years after surgery? A nationwide cohort.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common obesity-related co-morbidity that routinely is treated by continuous proton pump inhibitor (PPI) therapy. A number of concerns have been raised regarding the risk of de novo GERD or exacerbation of preexisting GERD after sleeve gastrectomy (SG). OBJECTIVE: To assess PPI use at 4 years after bariatric surgery. SETTING: French National Health Insurance. METHODS: Data were extracted from the French National Health Insurance database. All adult obese patients who had undergone gastric bypass (GBP) (n = 8250) or SG (n = 11,923) in 2011 in France were included. Patients were considered to be on continuous PPI therapy when PPIs were dispensed≥6 times per year. Logistic regression models were used to compute odds ratios for potential risk factors for PPI reimbursement 4 years after surgery. RESULTS: Overall, continuous use of PPIs increased from baseline to 4 years after SG and GBP, from 10.9% to 26.5% (P<.001) and from 11.4% to 21.9% (P<.001), respectively. Among patients who underwent PPI therapy before surgery, those who had undergone SG were more likely to continue PPI therapy 4 years after surgery compared with those who underwent GBP (72.7% versus 59.2%; P<.001). In multivariate analyses, the major risk factors for persistent continuous PPI treatment 4 years after surgery were the following: SG (odds ratio [OR] = 1.87; 95% confidence interval [CI] 1.55-2.25), higher body mass index (OR 1.85; 95% CI 1.35-2.5), and preoperative antidepressant treatment (OR 1.89; 95% CI 1.56-2.29). CONCLUSION: At a nationwide scale, continuous PPI treatment is used by 1 of 10 obese patients before bariatric surgery, but by 1 of 4 patients 4 years after surgery. SG compared with GBP, higher body mass index, and other coexisting conditions are the 3 major risk factors for medium-term continuous PPI therapy.

Current challenges in providing bariatric surgery in France: A nationwide study.

Bariatric surgery is a well-accepted procedure for severe and massive obesity management. We aimed to determine trends, geographical variations, and factors influencing bariatric surgery and the choice of procedure in France in a large observational study.The Health Insurance Fund for Salaried Workers (Caisse National Assurance Maladie Travailleurs Salariés) covers about 86% of the French population. The Système National d'Information Inter-régimes de l'Assurance Maladie database contains individualized and anonymized patient data on all reimbursements for healthcare expenditure. All types of primary bariatric procedures (Roux-en-Y gastric bypass [RYGB] or omega loop, adjustable gastric banding [AGB], or longitudinal sleeve gastrectomy [LSG]) performed during 2011 to 2013 were systematically recorded. Surgical techniques performed by region of residence and age-range relative risks with 95% confidence intervals of undergoing LSG or RYGB versus AGB were computed.In 2013, LSG was performed more frequently than RYGB and AGB (57% vs 31% and 13%, respectively). A total of 41,648 patients underwent a bariatric procedure; they were predominantly female (82%) with a mean (±standard deviation) age of 40 (±12) years and a body mass index ≥40 kg/m for 68% of them. A total of 114 procedures were performed in patients younger than 18 years and 2381 procedures were performed in patients aged 60 years and older. Beneficiaries of the French universal health insurance coverage for low-income patients were more likely to undergo surgery than the general population. Large nationwide variations were observed in the type choice of bariatric surgical procedures. Significant positive predictors for undergoing RYGB compared to those for undergoing AGB were as follows: referral to a center performing a large number of surgeries or to a public hospital, older age, female gender, body mass index ≥50 kg/m, and treatment for obstructive sleep apnea syndrome, diabetes, or depression. Universal health insurance coverage for low-income patients was inversely correlated with the probability of RYGB.Differences in access to surgery have been observed in terms of the patient's profile, geographical variations, and predictors of types of procedures. Several challenges must be met when organizing the medical care of this growing number of patients, when delivering surgery through qualified centers while assuring the quality of long-term follow-up for all patients.

Obesity Management in Europe: Current Status and Objectives for the Future.

OBJECTIVE: This study aims at assessing the status of obesity management in the European region and identifying future goals and objectives of professionals working in the field of obesity. METHODS: Presidents of all 31 EASO-affiliated (EASO = European Association for the Study of Obesity) national associations for the study of obesity were asked to invite 5 obesity experts from their country to participate in a survey. A total of 74 obesity professionals out of 23 countries participated. Questions addressed the development of guidelines, the status of obesity management, and goals and objectives for the future in obesity management. Further, EASO's three vice-presidents participated in in-depth, semi-structured interviews, in which they were asked to provide their reflection on the survey data. RESULTS: Most countries define obesity as a clinical and chronic disease, but various differences in obesity management standards exist across Europe. Existing guidelines mainly focus on the acute treatment of obesity rather than on long-term approaches. CONCLUSION: Multidisciplinary approaches for obesity management and the collaboration between general practitioners and hospitals as well as between professionals at the local level and networks of obesity management centers need to be improved across Europe. Good practices and evidence are available.

[Bariatric surgery in teenagers]. / CHIRURGIE DE L'OBÉSITÉ CHEZ L'ENFANT ET L'ADOLESCENT.

Bariatric surgery in teen-agers is increasing. This surgical option in the severely obese adolescent raises a series of questions on clinical pathway and ethics. It should be realized in highly specialized centers gathering skills in bariatric surgery, pediatric endocrinology and nutrition and psychology. It is a longstanding multifocal and proactive management including the transition to adulthood. Expert centers should be identified.

Medication cost is significantly reduced after Roux-en-Y gastric bypass in obese patients.

BACKGROUND: This study aims to determine the influence of Roux-en-Y gastric bypass (RYGB) on medication-related costs. METHODS: The study analyzed the types, dosages, and costs of drugs and medical devices prescribed before and after surgery (1, 3, 6, and 12 months and yearly thereafter) in patients who underwent RYGB between June 2004 and May 2010 and had an outpatient visit between December 2009 and May 2010 at Pitié-Salpêtrière University Hospital, Paris, France. RESULTS: The cohort included 143 patients (78 % female; mean age, 42.9 years; mean BMI, 48.6 kg/m(2)). Total prescription costs were significantly lower (-32 %, p < 0.001) 1 year after RYGB compared with preoperative costs. However, the cost for medications to prevent RYGB side effects (in particular nutritional deficiencies) displayed a 36-fold increase in the first month postsurgery, but then decreased progressively over time. Importantly, the cost related to the treatment of the two most frequent obesity-related diseases significantly decreased 1 year after surgery. Indeed, prescription costs for treatment of type 2 diabetes (T2D) and obstructive sleep apnea (OSA) (namely CPAP therapy considered as the gold standard treatment) were reduced 1 year after surgery by 85 and by 63 % (both p < 0.001), respectively. We also observed a trend toward a decrease in the prescription costs of other obesity-related diseases, although it did not reach significance in our cohort. CONCLUSIONS: Considering medication to treat both obesity-related diseases and prevention of secondary effects of bariatric surgery, we observed that overall postoperative medication costs were significantly reduced one year after surgery, especially for T2D and OSA.

ZHENG May Contribute to Obesity Phenotypes Based on Body Composition: A Pilot Study on the Traditional Chinese Medicine Approach.

Objective. Obesity therapy needs new approaches to complement current phenotyping systems. This study aims to assess associations between the Traditional Chinese Medicine (TCM) ZHENG and obesity phenotypes. Methods. We assessed medical history and habitual physical activity and measured body composition, fasting plasma glucose and insulin, and lipids. We collected TCM data through face-to-face interview. ZHENG elements (essentials and locations) were identified by TCM practitioner. Primary ZHENG was assessed by cluster analysis. Results. In 140 consecutive subjects enrolled in a university clinic (body mass index (BMI): 39.9 ± 5.8 kg/m2), ZHENG essentials were identified as "QiXu," "Re," "YinXu," and "TanShi" (totally 86.8%). Locations were "Shen," "Wei," "Pi," and "Gan" (totally 91.8%). Four types of primary ZHENG were identified: A (37.1% of subjects), B (16.5%), C (35.7%), and D (10.7%). Subjects in type D showed elevated BMI, total fat mass (FM), FM index, trunk FM, and less physical activity, as compared with others. Subjects in type B changed regional body composition (reduced trunk FM% and elevated appendicular FM%). Biological parameters did not differ across primary ZHENG clusters. Conclusions. Obesity phenotypes based on body composition differ according to ZHENG in obese patients. This study is a first step toward understanding the contribution of TCM to obesity phenotyping.

Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for treating morbid obesity and results in weight-loss and improvements in metabolism and inflammation. OBJECTIVE: We examined the impact of RYGB on modifications of gut microbiota and its potential associations with changes in gene expression in white adipose tissue (WAT). DESIGN: Gut microbiota were profiled from fecal samples by using pyrosequencing in morbidly obese individuals, explored before (0 mo), 3 mo after, and 6 mo after RYGB. WAT gene expression was studied at 0 and 3 mo. We explored associations between microbial genera and differentially expressed genes in WAT and clinical markers. RESULTS: The richness of gut microbiota increased after RYGB; 37% of increased bacteria belonged to Proteobacteria. The associations between gut microbiota composition and WAT gene expression increased after RYGB. Fourteen discriminant bacterial genera (7 were dominant and 7 were subdominant) and 202 WAT genes changed after RYGB. Variations in bacterial genera correlated with changes in both clinical phenotype and adipose tissue gene expression. Some genes encode metabolic and inflammatory genes. Almost half of the correlations were independent of the change in calorie intake. CONCLUSION: These results show an increase in gut microbiota richness and in the number of associations between gut microbiota and WAT genes after RYGB in obesity. Variations of gut microbiota were associated with changes in WAT gene expression. These findings stimulate deeper explorations of the mechanisms linking gut microbiome and WAT pathological alterations in human obesity and its changes after weight loss.

Growth hormone therapy for children and adolescents with Prader-Willi syndrome is associated with improved body composition and metabolic status in adulthood.

CONTEXT: Children with Prader-Willi syndrome (PWS) who receive GH treatment have improved growth and body composition; however, data are lacking for adults when treatment is discontinued after completion of growth. OBJECTIVES: Our aim was to compare body composition and metabolic status in adults with PWS according to GH treatment in childhood and adolescence. DESIGN: 64 adults (mean age: 25.4 years) with a genetic diagnosis of PWS were evaluated: 20 received GH in childhood (T), which had been discontinued at the time of this study, and 44 did not receive GH (C). Mean duration of treatment in the T group was 4.4 ± 2.7 years, age at baseline was 11.8 ± 2.7 years, mean time between the end of treatment and the current evaluation was 7.0 ± 4.4 years. MAIN OUTCOMES MEASURES: Dual-energy X-ray absorptiometry was used to assess body composition and fasting biological analyses evaluated metabolic status. RESULTS (MEAN ± SD): Body mass index and percentage of fat mass were significantly lower in the T group (32.4 ± 10.3 vs 41.2 ± 11.1 kg/m(2), P = 0.05 and 44.0 ± 9.6 vs 50.1 ± 7.2%, P = 0.02, respectively). Insulinemia and HOMA-IR in non-diabetic subjects were significantly lower in the T group (5.8 ± 5.9 vs 13.9 ± 11.6 µUI/ml, P = 0.03, and 1.6 ± 1.3 vs 2.7 ± 2.1, P = 0.04, respectively). Non-diabetic and diabetic subjects from the T group had a significantly lower HbA1c. Lipid profiles were similar between groups. CONCLUSIONS: GH treatment in childhood and adolescence is associated with significantly decreased body mass index and improved body composition and metabolic status in adults with PWS at several years after discontinuing treatment.

Homozygous leptin receptor mutation due to uniparental disomy of chromosome 1: response to bariatric surgery.

CONTEXT: Severe early-onset obesity with major hyperphagia associated with hypogonadotropic hypogonadism is recognized as the main clinical presentation of leptin (LEP) or LEP receptor (LEPR) gene complete deficiency. In a few reported cases, homozygous mutations have been found in patients from consanguineous families. Care of LEPR-deficient patients is complicated because they cannot benefit from LEP treatment. Furthermore, gastric surgery may not be recommended in such genetic hypothalamic obesity. OBJECTIVE: We investigated in a morbidly obese patient the genetic origin of his obesity and evaluated the benefit of bariatric surgery in this case. SUBJECT AND METHODS: The patient exhibited severe early-onset obesity with hyperphagia and delayed puberty in a nonobese family. He had clinical and hormonal follow-up from 3 to 26 years of age. Gastroplasty procedures were undertaken when he was 16 and 18 years old. LEPR genetic analysis of the patient and his relatives was performed. RESULTS: A new homozygous LEPR sequence frameshift, predicted to generate a truncated protein from a premature stop codon in exon 14, was identified in the proband inherited from two paternal copies of chromosome 1 (isodisomy). Vertical ring gastroplasty was sufficient to induce and maintain a 40-kg weight loss into adulthood. CONCLUSION: We described the first case of a patient with chromosome 1 uniparental isodisomy revealed by molecular analysis of LEPR. In this case, gastroplasty may be partially effective for weight control as illustrated.

Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and being overweight is a significant risk factor. The aim was to build an algorithm along with a scoring system for histopathologic classification of liver lesions that covers the entire spectrum of lesions in morbidly obese patients. A cohort of 679 obese patients undergoing liver biopsy at the time of bariatric surgery was studied. An algorithm for segregating lesions into normal liver, NAFLD, or nonalcoholic steatohepatitis (NASH) was built based on semiquantitative evaluation of steatosis, hepatocellular ballooning, and lobular inflammation. For each case, the SAF score was created including the semiquantitative scoring of steatosis (S), activity (A), and fibrosis (F). Based on the algorithm, 230 obese patients (34%) were categorized as NASH, 291 (43%) as NAFLD without NASH, and 158 (23%) as not NAFLD. The activity score (ballooning + lobular inflammation) enabled discriminating NASH because all patients with NASH had A ≥ 2, whereas no patients with A < 2 had NASH. This score was closely correlated with both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P < 0.0001, analysis of variance [ANOVA]). Comparison of transaminase levels between patients with normal liver and pure steatosis did not reveal significant differences, thus lending support to the proposal not to include steatosis in the activity score but to report it separately in the SAF score. In the validation series, the interobserver agreement for the diagnosis of NASH was excellent (κ = 0.80) between liver pathologists. There was no discrepancy between the initial diagnosis and the diagnosis proposed using the algorithm. CONCLUSION: We propose a simple but robust algorithm for categorizing liver lesions in NAFLD patients. Because liver lesions in obese patients may display a continuous spectrum of histologic lesions, we suggest describing liver lesions using the SAF score.

Dynamic relations between sedentary behavior, physical activity, and body composition after bariatric surgery.

BACKGROUND: Physical activity has been shown to increase following obesity surgery; however, changes in sedentary behavior in this setting are not known. Our aim was to describe changes in both physical activity and sedentary behavior of obese patients after gastric bypass (GBP) and their relationships with changes in body composition. METHODS: Physical activity, time spent watching TV as typical sedentary behavior (self-report), and body composition (DXA) were assessed before and 6 and 12 months after GBP in 86 obese patients (67 women, 24-66 years old, BMI 41.3-53.5 kg/m(2)). RESULTS: One year after GBP (mean loss of weight -37.1 kg, fat mass -25.7 kg, lean body mass -9.4 kg), leisure-time physical activity (LTPA) significantly increased from 2.0 (SD 3.7) to 3.8 (5.4) h/week and from 7.2 (12.5) to 14.1 (20.1) MET-h/week (MET: metabolic equivalent task), the number of LTPA performed increased from 1.3 (1.3) to 1.8 (1.4), and TV time decreased from 3.0 (1.6) to 2.4 (1.4) h/day (all p < 0.05). The ranking of the most frequently performed LTPA did not change. Positive associations were observed between the increase in lean body mass and (1) the increase in LTPA and (2) the decrease in TV watching. Inverse relationships were found for changes in fat mass. CONCLUSIONS: Together with increased LTPA, this study shows a decrease in sedentary behavior after GBP, which appears related to favorable changes in body composition. These observations are important to design future intervention studies, including physical activity and sedentary occupations aiming to optimize the care of patients after bariatric surgery.

Structural and inflammatory heterogeneity in subcutaneous adipose tissue: relation with liver histopathology in morbid obesity.

BACKGROUND & AIMS: In addition to total body fat, the regional distribution and inflammatory status of enlarged adipose tissue are strongly associated with metabolic co-morbidities of obesity. We recently showed that the severity of histological liver lesions related to obesity increases with the amount of macrophage accumulation in visceral adipose tissue (VAT), while no association was found with the subcutaneous adipose tissue (SAT). In the abdominal region, SAT is anatomically divided into two layers, i.e. superficial (sSAT) and deep (dSAT). The aim of the present study was to test the hypothesis that these distinct compartments differentially contribute to hepatic alterations in obesity. METHODS: Biopsies of the liver, sSAT, dSAT, and VAT were collected in 45 subjects with morbid obesity (age 43.7±1.6 years; BMI 48.5±1.2kg/m(2)) during bariatric surgery. Large scale gene expression analysis was performed to identify the pathways that discriminate sSAT from dSAT. Adipose tissue macrophages were quantified by immunohistochemistry using HAM56 antibody in subjects scored for liver histopathology. RESULTS: An inflammatory gene pattern discriminates between sSAT and dSAT. dSAT displayed an intermediate level of macrophage accumulation between sSAT and VAT. The abundance of macrophages in dSAT, but not in sSAT, was significantly increased in patients with non-alcoholic steatohepatitis (NASH) and/or fibroinflammatory hepatic lesions. CONCLUSIONS: These data show distinct gene signature and macrophage abundance in the two compartments of SAT, with dSAT more closely related to VAT than to sSAT in terms of inflammation and relation with the severity of liver diseases in morbid obesity.

Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese.

BACKGROUND & AIMS: Morbid obesity is frequently associated with low grade systemic inflammation, increased macrophage accumulation in adipose tissue (AT), obstructive sleep apnea (OSA), and nonalcoholic fatty liver disease (NAFLD). It has been suggested that chronic intermittent hypoxia (CIH) resulting from OSA could be an independent factor for early stage of NAFLD in addition to other well-recognized factors (dyslipidemia or insulin resistance). Moreover, macrophage accumulation in AT is associated with local hypoxia in fat tissue. We hypothesized that the association between CIH and morbid obesity could exert additional specific deleterious effects both in the liver and adipose tissues. METHODS: One hundred and one morbidly obese subjects were prospectively recruited and underwent bariatric surgery during which a liver needle biopsy as well as surgical subcutaneous and omental AT biopsies were obtained. Oxygen desaturation index (ODI) quantified the severity of nocturnal CIH. RESULTS: Histopathologic analysis of liver biopsies demonstrated that NAFLD lesions (ballooning of hepatocytes, lobular inflammation), NAFLD activity score (NAS), and fibrosis were significantly more severe in patients with the highest ODI tertile (p values ≤0.001 for all hepatic lesions). In multivariate analysis, after adjustment for age, obesity, and insulin resistance status, CIH remained independently associated with hepatic fibrosis, fibroinflammation, and NAS. By contrast, no association was found between CIH, macrophage accumulation, and adipocytes size in both subcutaneous and omental adipose tissue. CONCLUSIONS: In morbidly obese patients, CIH was strongly associated with more severe liver injuries but did not worsen obesity induced macrophage accumulation in adipose tissue depots.

Etonorgestrel concentrations in morbidly obese women following Roux-en-Y gastric bypass surgery: three case reports.

BACKGROUND: Pregnancy should be avoided for 12 to 18 months after Roux-en-Y gastric bypass (RYGB) surgery. The etonorgestrel (ENG)-releasing implant (Implanon®) may represent a safe and effective contraceptive method in morbidly obese women who are candidates for bariatric surgery. In addition, the subcutaneous delivery of steroid is unaffected by malabsorptive surgery. METHODS: Three cases of young women with ENG-releasing implant are reported. The device was inserted 1-2 months prior to RYGB. RESULTS: Their initial weights were 130 to 176 kg, and the mean weight loss was 33.6 kg at 6 months. The concomitant serum ENG concentrations decreased currently with weight loss but remained above the minimum concentration required for effective contraceptive effect of the implant for at least 6 months following RYGB (average, 170 pg/mL). The concentrations observed before weight loss were lower than in normal-weight women, but decreases in ENG concentrations following implant insertion were similar. CONCLUSION: These unique data in morbidly obese women highlight the need for further pharmacokinetic studies of contraceptive agents in obese women during weight loss.