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.

[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.

[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.

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.

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.

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.

Benefits of massive weight loss on symptoms, systemic inflammation and cartilage turnover in obese patients with knee osteoarthritis.

OBJECTIVE: To investigate the effect of massive weight loss on (1) knee pain and disability, (2) low-grade inflammation and metabolic status and (3) joint biomarkers in obese patients with knee osteoarthritis (OA). METHODS: 140 patients involved in a gastric surgery programme were screened for painful knee OA, and 44 were included (age 44 ± 10.3 years, body mass index (BMI) 50.7 ± 7.2 kg/m(2)). Clinical data and biological samples were collected before and 6 months after surgery. RESULTS: Before surgery, interleukin 6 (IL-6) levels were correlated with levels of high-sensitivity C reactive protein (hsCRP) (p=0.006) and Helix-II (p=0.01), a biomarker of cartilage turnover, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score (p=0.03). Surgery resulted in substantial decrease in BMI (-20%). Levels of insulin and insulin resistance were decreased at 6 months. Knee pain decreased after surgery (24.5 ± 21 mm vs 50 ± 26.6 mm; p<0.001), and scores on all WOMAC subscales were improved. Levels of IL-6 (p<0.0001), hsCRP (p<0.0001), orosomucoid (p<0.0001) and fibrinogen (p=0.04) were decreased after surgery. Weight loss resulted in a significant increase in N-terminal propeptide of type IIA collagen levels (+32%; p=0.002), a biomarker of cartilage synthesis, and a significant decrease in cartilage oligomeric matrix protein (COMP) (-36%; p<0.001), a biomarker of cartilage degradation. Changes in COMP concentration were correlated with changes in insulin levels (p=0.02) and insulin resistance (p=0.05). CONCLUSION: Massive weight loss improves pain and function and decreases low-grade inflammation. Change in levels of joint biomarkers with weight loss suggests a structural effect on cartilage.

Evolution of obesity prevalence in France: an age-period-cohort analysis.

BACKGROUND: A rapid increase in the prevalence of obesity has been reported in France since 1990. We investigated the impact of birth cohort on the changes in obesity prevalence after taking into account age and survey period. METHODS: We analyzed data from 4 national surveys in 1997, 2000, 2003, and 2006. For each survey, self-reported data on weight and height were recorded on mailed questionnaires sent to a sample of 20,000 households, representative of the French population. Obesity was defined according to World Health Organization criteria as body mass index >or=30 kg/m. We modeled the prevalence of obesity using logistic regression with age, cohort, and period as explanatory variables. As these variables are linearly dependent, only nonlinear effects can be estimated uniquely and interpreted, after including specific chosen constraints in the models. RESULTS: There was a progressive increase in the prevalence of obesity between 1997 and 2006, attributable either to a period effect or to a cohort effect. There was a substantial departure from a linear trend for the cohort effect only, which seemed to be stronger in women: there was an acceleration in the prevalence of obesity with birth cohort for individuals born after the mid-1960s, in both sexes. CONCLUSIONS: Our results are consistent with previous studies in other countries. Compared with older generations, men and women born in the late 1960s may have been subject to early exposures that increased their lifelong susceptibility to obesity.

Latent variables and structural equation models for longitudinal relationships: an illustration in nutritional epidemiology.

BACKGROUND: The use of structural equation modeling and latent variables remains uncommon in epidemiology despite its potential usefulness. The latter was illustrated by studying cross-sectional and longitudinal relationships between eating behavior and adiposity, using four different indicators of fat mass. METHODS: Using data from a longitudinal community-based study, we fitted structural equation models including two latent variables (respectively baseline adiposity and adiposity change after 2 years of follow-up), each being defined, by the four following anthropometric measurement (respectively by their changes): body mass index, waist circumference, skinfold thickness and percent body fat. Latent adiposity variables were hypothesized to depend on a cognitive restraint score, calculated from answers to an eating-behavior questionnaire (TFEQ-18), either cross-sectionally or longitudinally. RESULTS: We found that high baseline adiposity was associated with a 2-year increase of the cognitive restraint score and no convincing relationship between baseline cognitive restraint and 2-year adiposity change could be established. CONCLUSIONS: The latent variable modeling approach enabled presentation of synthetic results rather than separate regression models and detailed analysis of the causal effects of interest. In the general population, restrained eating appears to be an adaptive response of subjects prone to gaining weight more than as a risk factor for fat-mass increase.

[Obesity, a disease]. / L'obésité, une maladie en soi.

Obesity has been considered as a disease by the World Health Organisation since 1997. It was previously considered a simple risk factor and a manifestation of consumer society. This recognition was based on several developments, including epidemiological data showing the worldwide spread of the disease; the increasing health expenditure due to the obesity-related increase in type 2 diabetes; and progress in pathophysiological concepts. Obesity is a chronic and progressive disease. Management approaches range from prevention to surgery, and must be adapted to the individual situation.

Association between omental adipose tissue macrophages and liver histopathology in morbid obesity: influence of glycemic status.

BACKGROUND/AIMS: Recently we showed that macrophage accumulation in omental adipose tissue is associated with liver fibro-inflammation in morbidly obese subjects. Here, we evaluated the influence of glycemic status and extended the analysis to the spectrum of obesity-linked liver damage. METHODS: Liver biopsies, subcutaneous and omental adipose tissue were collected in 132 obese subjects during gastric bypass surgery. HAM56+ adipose tissue macrophages were counted in subjects classified by liver histopathology and by their degree of insulin resistance. RESULTS: In the whole population, the number of omental macrophages increased with the score of steatosis, the non-alcoholic fatty liver disease activity score, the stage of fibrosis and with fibro-inflammation index. None of these relationships were significant with subcutaneous macrophage count. In insulin-sensitive participants, omental macrophages accumulation was higher in subjects with high indexes of fibro-inflammation (p=0.012 vs. low indexes). In insulin-resistant including type 2 diabetic participants, omental macrophage count was higher both in subjects with high scores of steatosis and in subjects with high indexes of fibro-inflammation (p<0.05 vs. low scores). CONCLUSIONS: Macrophage accumulation in omental adipose tissue is associated with aggravated steatosis and fibro-inflammation in insulin-resistant obese subjects independently of altered glycemic status.

In obese and non-obese adults, the cis-regulatory rs361072 promoter variant of PIK3CB is associated with insulin resistance not with type 2 diabetes.

We recently reported that rs361072, a promoter C/T variant of p110beta, the catalytic subunit of PI3-kinase, was associated with a protection from insulin resistance (IR) in Caucasian adolescents in proportion of their body mass. We tested if this cis-regulatory QTL is associated with IR and type 2 diabetes in 7885 middle-aged obese and non-obese adults of European ancestry. We genotyped rs361072 in 1139 non-diabetic obese (NDO) European adults, in whom IR was estimated by the HOMA-IR index. We also studied 427 type 2 diabetic obese adults (DO) and 424 diabetic non-obese (DNO) adults to test whether their disease status was associated with a decreased prevalence of the protective variant. The prevalence of rs361072 and association with IR was also examined in 5895 non-obese non-diabetic adults (NDNO). rs361072 was associated with HOMA-IR (p=4.10(-4)) in NDO, so that C/C patients had a 17% decrease of this index (p=0.002). A statistical trend (p=1.1.10(-2)) for the same genotypic differences was also observed in NDNO adults, but of insignificant magnitude (4.2%). The distribution of rs361072 genotype was comparable in NDO, DO, DNO and NDNO individuals. Allele C of rs361072 is associated with a protection from IR in obese and non-obese adults, but has no significant effect, however, on diabetes risk in obese or non-obese Europeans.

Downward trends in the prevalence of childhood overweight in the setting of 12-year school- and community-based programmes.

OBJECTIVE: A school-based nutrition information programme was initiated in 1992 in two towns in northern France (Fleurbaix and Laventie, FL) and was followed by a number of community-based interventions. We took the opportunity to measure the outcomes in terms of childhood obesity and overweight over the next 12 years. DESIGN: Repeated, cross-sectional, school-based survey. For the school years beginning in 1992, 2000, 2002, 2003 and 2004, the height and weight of all 5- to 12-year-old children attending school were measured in FL. In 2004, the same assessments were made in two comparison towns with similar socio-economic characteristics but no intervention. SETTING: Fleurbaix and Laventie (intervention towns), Bois-Grenier and Violaines (comparison towns), northern France. SUBJECTS: In 2002, 2003 and 2004, respectively 515, 592 and 633 children were measured in FL (participation rate of 95-98% of all eligible individuals); in the comparison towns, 349 children were measured in the 2004 school year (98% of the towns' school population). RESULTS: After an initial increase, trends in mean BMI and prevalence of overweight started to reverse. Compared with 2002, the age-adjusted OR for overweight in FL was significantly lower in 2003 and 2004 (but for girls only). In the 2004 school year, the overweight prevalence was significantly lower in FL (8.8%) than in the comparison towns (17.8%, P < 0.0001). CONCLUSION: These data suggest that, over a long period of time, interventions targeting a variety of population groups can have synergistic effects on overweight prevalence. This gives hope that it is possible to reverse trends towards increasing overweight by actions at the community level.

Cognitive restraint, uncontrolled eating and emotional eating: correlations between parent and adolescent.

The purpose of this study was to examine, in a general population, the resemblance in eating behaviour between adolescents and their parents. This study was based on the first examination of a community-based epidemiological study in Northern France. Subjects were offspring aged 14-22 years (135 boys and 125 girls) and their parents (174 fathers and 205 mothers). The Three-Factor Eating Questionnaire Revised 18-item version (TFEQ-R18) identified three aspects of eating behaviour: cognitive restraint of eating, uncontrolled eating and emotional eating. Familial resemblance in eating behaviour was measured by partial Spearman's correlations, adjusted for age and body mass index. Sons' uncontrolled eating was positively related to fathers' cognitive restraint of eating (r = 0.36), but not to fathers' uncontrolled eating (r = 0.07), nor to mothers' eating behaviour. Sons' cognitive restraint of eating was related to no parental eating behaviour scores. In daughters, cognitive restraint of eating was positively related to mothers' uncontrolled eating (r = 0.26), but not to mothers' cognitive restraint of eating (r = 0.13). Daughters' uncontrolled eating and emotional eating were positively associated with the same scores in mothers. Finally, daughters' eating behaviour was not related to fathers' eating behaviour. In conclusion, correlations in eating behaviour were higher with the parent of the same gender, and eating behaviours in adolescents seem to reflect opposition to parents' behaviour more than familial resemblance.

[New insights into obesity]. / Nouveaux regards sur les déterminants de i'obésité.

Central to obesity is an energy imbalance due to increased calorie intake and/or decreased energy expenditure, as well as a genetic or non genetic biological predisposition. New advances in obesity research point to a role of primary changes in fat storage capacity. Modifications of the cellular composition and structure of adipose tissue, characterized by inflammation and fibrosis, can lead to an "organ disease" that is partially irreversible, thus explaining long-term treatment resistance. This organ disease may lead to local and systemic disorders. A possible role of the gut flora is one especially interesting line of research.

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.

Association of arterial stiffness and endothelial dysfunction with metabolic syndrome in obese children.

OBJECTIVE: We investigated whether metabolic syndrome, defined in 3 different ways (2 commonly used and 1 novel) is associated with arterial alterations in obese children. STUDY DESIGN: The study group comprised 384 obese children age 2.5 to 18 years. Blood pressure, fasting blood glucose, blood insulin, plasma lipids, and body composition were measured. Noninvasive ultrasound measurements were obtained in 161 patients to investigate arterial mechanical properties and endothelial function. RESULTS: The prevalence of metabolic syndrome was 10.4%. Intima-media thickness correlated positively with low-density lipoprotein cholesterol (r = .21; P < .01) and negatively with high-density lipoprotein cholesterol (r = -.17; P < .05). In adolescents (11 to 18 years), cross-sectional vascular compliance correlated negatively with abdominal fat (r = -.22; P = .02). The only synergistic effects among individual metabolic syndrome components was an effect of insulinemia and systolic blood pressure on cross-sectional compliance (4.05; P < .05). No significant difference in vascular variables was found between the patients with and without metabolic syndrome using any of the 3 definitions. CONCLUSION: Metabolic syndrome in obese children is not related to arterial variables, whereas several of its individual components are associated with vascular alterations. These data suggest that the value of the metabolic syndrome as a predictor of future cardiovascular events in children remains to be prospectively evaluated. In the meantime, individual cardiovascular risk factors should be evaluated and controlled.

Leptin therapy for partial lipodystrophy linked to a PPAR-gamma mutation.

AIMS/HYPOTHESIS: Partial lipodystrophy (PL) is most commonly characterized by loss of subcutaneous fat in the extremities with preservation of truncal fat and is associated with insulin resistance, diabetes and hyperlipidaemia. Recombinant human leptin (r-metHuLeptin) therapy has been shown to be effective in treating metabolic abnormalities associated with congenital or acquired generalized lipodystrophy and PL associated with lamin A/C (LMNA) gene mutations or highly active antiretroviral therapy (HAART). Our aim was to assess the effectiveness of leptin therapy in treating metabolic complications of PL associated with heterozygous peroxisome proliferator activated receptor gamma (PPARG) mutations. This is the first report to detail the clinical response of a patient with PL due to a PPARG mutation treated with r-metHuLeptin. METHODS: A 36-year-old female with PL associated with a heterozygous PPARG mutation complicated by poorly controlled diabetes and severe, refractory hypertriglyceridaemia was enrolled in a National Institutes of Health (NIH) protocol to evaluate the role of r-metHuLeptin in lipodystrophy. The patient received escalating doses of r-metHuLeptin until a dose 0.12 mg/kg/day was reached. Metabolic parameters, including serum chemistries, fasting blood glucose, glycated haemoglobin (HbA1c), lipid profile, an oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), liver volume, percentage body fat and energy expenditure were followed at regular time intervals over 18 months of therapy. RESULTS: Eighteen months of r-MetHuLeptin therapy was associated with a marked improvement in glucose homeostasis as evidenced by normalization of the fasting blood glucose (baseline = 8.3 mmol/l; 18 months = 4.9 mmol/l), lowering of HbA1c (baseline = 9.9%; 18 months = 7.2%) and improved tolerance to an oral glucose load. In addition, a striking amelioration in the patient's refractory, severe hypertriglyceridaemia was observed (baseline = 21.15 mmol/l; 18 months = 5.96 mmol/l). CONCLUSION: r-MetHuLeptin is effective in treating metabolic complications associated with PL due to PPARG mutations. In the context of previously published work, our findings suggest that the response to r-MetHuLeptin is independent of the aetiology in lipodystrophy.

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.

Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity.

In human obesity, white adipose tissue (WAT) is enriched in macrophages. How macrophage infiltration in WAT contributes to the complications of obesity is unknown. This study tested the hypothesis that recruitment of macrophages in omental WAT is associated with hepatic damage in obese patients. Paired biopsies of subcutaneous and omental WAT and a liver biopsy were collected during gastric surgery in 46 obese women and 9 obese men (BMI 47.9 +/- 0.93 kg/m(2)). The number of HAM56+ macrophages in WAT was quantified microscopically, and correlations with clinical and biological parameters and histological liver pathology were investigated. There were twice as many macrophages in omental as in subcutaneous WAT (P<0.0001). After adjustment for age, omental WAT macrophage infiltration was correlated to fasting glucose and insulin, quantitative insulin sensitivity check index, triglycerides, aspartate aminotransferase (AST), and gamma-glutamyltranspeptidase. We propose an easy equation to estimate the amount of macrophages in omental WAT. Increased macrophage accumulation specifically in omental WAT was associated with hepatic fibroinflammatory lesions (P=0.01). The best predictive model for the severity of hepatic damage includes adiponectinemia, AST, and omental WAT macrophages. These data suggest that the presence of macrophages in omental WAT participates in the cellular mechanisms favoring hepatic fibroinflammatory lesions in obese patients.