Dramatic impact of morbid obesity on child lung development.

OBJECTIVE: To assess the respiratory function and sleep characteristics of obese adults and children. METHODS: All patients with non-syndromic, severe obesity (BMI ≥3 z-scores for children and ≥40.00kg/m2 for adults), referred for pulmonary function tests at Lille University Hospital, were retrospectively included. RESULTS: A total of 69 children (mean±SD BMI 36.8±6.7 and mean BMI z-score 4.7±1.0) and 70 adults were included (mean BMI 45.7±6.2). Metabolic syndrome was diagnosed in 13 children (26%) and 40 adults (80%). Reduced lung volumes were observed in 34 children (50.0%) and 16 adults (24.0%) and both the mean functional residual capacity (FRC) and the mean residual volume (RV) were lower in children than in adults (FRC: -1.7±2.1 z-score in children vs. -1.0±1.1 in adults, P=0.026; and RV: -0.8±1.2 z-score in children vs. -0.1±1.1 in adults, P=0.002). The prevalence of severe obstructive sleep apnea syndrome was greater in adults (40.7% vs. 18.8%, P=0.007). Children had a higher average oxygen saturation (median of 96.0% [91.0-98.0] vs. 93.0% [76.0-97.0] in adults, P<0.0001). CONCLUSION: Obesity has consequences for lung volumes in children; however, a longitudinal study is needed to determine the impact on pulmonary expansion and growth.

Revisiting the evolutionary origins of obesity: lazy versus peppy-thrifty genotype hypothesis.

The recent global obesity epidemic is attributed to major societal and environmental changes, such as excessive energy intake and sedentary lifestyle. However, exposure to 'obesogenic' environments does not necessarily result in obesity at the individual level, as 40-75% of body mass index variation in population is attributed to genetic differences. The thrifty genotype theory posits that genetic variants promoting efficient food sequestering and optimal deposition of fat during periods of food abundance were evolutionarily advantageous for the early hunter-gatherer and were positively selected. However, the thrifty genotype is likely too simplistic and fails to provide a justification for the complex distribution of obesity predisposing gene variants and for the broad range of body mass index observed in diverse ethnic groups. This review proposes that gene pleiotropy may better account for the variability in the distribution of obesity susceptibility alleles across modern populations. We outline the lazy-thrifty versus peppy-thrifty genotype hypothesis and detail the body of evidence in the literature in support of this novel concept. Future population genetics and mathematical modelling studies that account for pleiotropy may further improve our understanding of the evolutionary origins of the current obesity epidemic.

Obesity genetics: insights from the Pakistani population.

The Pakistani population is extensively diverse, indicating a genetic admixture of European and Central/West Asian migrants with indigenous South Asian gene pools. Pakistanis are organized in different ethnicities/castes based on cultural, linguistic and geographical origin. While Pakistan is facing a rapid nutritional transition, the rising prevalence of obesity is driving a growing burden of health complications and mortality. This represents a unique opportunity for the research community to study the interplay between obesogenic environmental changes and obesity predisposing genes in the time frame of one generation. This review recapitulates the ancestral origins of Pakistani population, the societal determinants of the rise in obesity and its governmental management. We describe the contribution of syndromic, monogenic non-syndromic and polygenic obesity genes identified in the Pakistani population. We then discuss the utility of gene identification approaches based on large consanguineous families and original gene × environment interaction study designs in discovering new obesity genes and causal pathways. Elucidation of the genetic basis of obesity in the Pakistani population may result in improved methods of obesity prevention and treatment globally.

How obesity relates to socio-economic status: identification of eating behavior mediators.

BACKGROUND: Socio-economic status (SES) is a strong determinant of eating behavior and the obesity risk. OBJECTIVE: To determine which eating and lifestyle behaviors mediate the association between SES and obesity. METHODS: We performed a case-control study of 318 obese people and 371 non-obese people in northern France. Ten eating behavior traits were assessed using the Three-Factor Eating Questionnaire Revised 21-Item and an eating attitude questionnaire (on plate size, the number of servings, reasons for stopping eating and the frequency of eating standing up, eating in front of the television set (TV) and eating at night). The SES score (in three categories) was based on occupation, education and income categories. Mediation analysis was performed using the test of joint significance and the difference of coefficients test. RESULTS: The age- and gender-adjusted obesity risk was higher for individuals in the low-SES groups (odds ratio (OR) (95% confidence interval (CI)=1.82 (1.48-2.24), P<0.0001). Additional servings were associated with a higher obesity risk (OR=3.43, P<0.0001). Cognitive restraint (P<0.0001) and emotional eating (P<0.0001) scores were higher in obese participants than in non-obese participants but did not depend on SES. Of the 10 potential factors tested, eating off a large plate (P=0.01), eating at night (P=0.04) and uncontrolled eating (P=0.03) significantly mediated the relationship between SES and obesity. CONCLUSION: Our results highlighted a number of obesogenic behaviors among socially disadvantaged participants: large plate size, uncontrolled eating and eating at night were significant mediators of the relationship between SES and the obesity risk.

[Infertility: A key time to follow a medical nutritional management. Our experience on 78 patients]. / Infertilité : moment clé pour entreprendre une prise en charge nutritionnelle médicale. Expérience lilloise sur 78 patientes.

OBJECTIVES: The prevalence of female obesity is increasing. Obesity leads to increased infertility and difficulties in the management of Assisted Reproductive Technology (ART). A specialized nutritional consultation was created in 2008 at University Hospital of Lille, to support infertile obese and overweight patients and to achieve a BMI below 35kg/m(2) before pregnancy. The aim of this retrospective study was to evaluate our practice of nutritional support on weight and pregnancy rate. METHODS: Seventy-eight obese or overweight patients, followed in nutrition and ART for at least two years, were compared to a control group of 119 normal weight patients. The nutritional strategy was mainly based on lifestyle changes, to establish healthier food and higher physical activity. RESULTS: The mean initial BMI was 37.5kg/m(2) vs 35.6kg/m(2) after nutritional support (significant weight loss, [P<0.001]). Obese or overweight patients had more frequently metabolic syndrome (P<0.01). The chances of pregnancy, after weight loss, were similar to the control group both in IUI and IVF/ICSI. However, gonadotropin doses were increased in the obese and overweight group (P=0.007). The hypocaloric diet was the most effective nutritional strategy to achieve a weight loss greater than 5% of initial weight (P=0.017). Regular physical activity practice allowed also more frequently to achieve this goal (P=0.074). Even after weight loss, a significant number of gestational diabetes (25% of pregnancies in our population) occurred in the obese or overweight group. CONCLUSION: This nutritional consultation promotes weight loss in infertile obese or overweight patients. The maternity desire is a strong motivational lever to weight loss, which leads to satisfying pregnancy rate.

[Contraception and obesity]. / Contraception et obésité.

The prevalence of obesity is increasing massively over several decades in industrialized countries. Obese women are sexually active but they use fewer contraceptive methods and are at high risk of unintended pregnancy. In addition, obesity is an important risk factor for venous thromboembolism events and arterial thrombosis (myocardial infarction and ischemic stroke). All of these data are to be considered in choosing a contraceptive method for obese women. Except depot medroxyprogesterone acetate injection, the progestin-only contraceptives (progestin only pills and etonogestrel subdermal implant) and the intra-uterine devices are the preferred contraceptive methods in obese women. The combined estrogen-progestin contraceptives (pill, patch and vaginal ring) may be proposed in very strict conditions (no other associated vascular risk factor). Obesity does not increase the risk of failure of most contraceptive methods. Bariatric surgery is a complex situation. It requires to program a possible pregnancy and contraception is needed for several months. Some bariatric surgical techniques such as by-pass can induce gastrointestinal malabsorption. In this situation, all oral contraceptives are not recommended because of a higher risk of failure.

Severe scurvy: an underestimated disease.

Scurvy is one of the oldest diseases in human history. Nowadays, although scurvy tends to become a forgotten disease in developed country, rare cases still occur, especially in people undergoing extreme diet, old people or children with poor diet and patients with malabsorption. We describe three cases of scurvy. The first case is a patient diagnosed with Crohn's disease, the second one is in a context of anorexia nervosa and drug addiction, and the third case is in a context of social isolation. Early recognition of scurvy can be difficult because symptoms may appear nonspecific and can mimic more common conditions. In any patient with spontaneous hematoma and purpura, in the context of nutritional disorder, scurvy should be systematically considered. As this disease can lead to severe complications, such as bone pain, heart failure or gastrointestinal symptoms, nothing should delay vitamin C supplementation, which is a simple and rapidly effective treatment.

Anti-sRAGE autoimmunity in obesity: downturn after bariatric surgery is independent of previous diabetic status.

AIM: Morbid obesity increases the risk of cardiovascular disease (CVD). The receptor for advanced glycation end-products (RAGE) is implicated in proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were described and found to be increased in diseases where RAGE is overexpressed. This study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly obese patients. METHODS: After exclusion based on specific criteria, 150 subjects (50 normoglycemics, 50 glucose-intolerants and 50 diabetics) were randomly recruited from a cohort of 750 obese patients (ABOS). Serum sRAGE and anti-sRAGE autoantibodies were measured before bariatric surgery. Sixty-nine patients were followed for up to 1year after gastric bypass, and their levels of sRAGE and anti-sRAGE autoantibodies measured. The control group consisted of healthy blood donors. RESULTS: Compared with controls, baseline levels of sRAGE and anti-sRAGE autoantibodies were significantly higher in all obese patients independently of glucose regulation (P<0.001). At 1year after gastric bypass, sRAGE and anti-sRAGE were decreased (P<0.001). The decrease in anti-sRAGE autoantibodies was correlated with an increase in high-density lipoprotein (HDL; P=0.02). CONCLUSION: Independently of previous diabetic status, morbid obesity increases sRAGE and anti-sRAGE levels. Weight loss after gastric bypass is followed by a decrease in both titres. The decrease in anti-sRAGE correlates with an increase in HDL.

Body distortions after massive weight loss: lack of updating of the body schema hypothesis.

Behavioural therapy and bariatric surgery often produce rapid, massive body weight loss that may impact a patient's ability to gauge his/her new body shape. Although the patient is aware of the weight loss, he/she continues to feel obese, as if there was a conflict between the previous body schema and the new one. Here, we report the case of a 40-year-old woman who developed major body distortions after massive weight loss. Psychometric and behavioural assessments revealed strong disturbances in several tasks involving body representation. In particular, we observed abnormal behaviour in a body-scaled action task. Our findings suggest that the rapidity of our patient's weight loss prevented her central nervous system from correctly updating the body schema.

[Impact of bariatric surgery on obstetric prognosis]. / Impact de la chirurgie bariatrique sur le pronostic obstétrical.

OBJECTIVES: Assessment of pregnancy outcomes after bariatric surgery and analysis of follow-up particularities of such pregnancies. PATIENTS AND METHODS: A retrospective study of 63 post-bariatric surgery pregnancies compared to 259 pregnancies of obese un-operated patients. Pregnancy outcomes, neonatal datas, delay influence between surgery and pregnancy beginning, bariatric surgery type and gastric banding (GB) loosening consequences were analysed. RESULTS: In the surgical brand were developed less gestational diabetes (DG) (P=0,05), deliveries were more often normal (P=0,004) and births shown less macrosomias and small for gestational age newborns (P=0,04). Neonatal state was improved among operated patients: less Apgar scores less than 7 at 1 minute (P=0,05) and less cord blood pH less than 7,2 (P=0,03). They gained more weight during the pregnancy (P=0,0003) and only 53% had a nutritional management and assessment. Patients with GB loosening gained more weight (P=0,0003). Lastly, there were no difference due to the different bariatric surgery techniques or nutritional follow-up in the pregnancy course and neonatal state. DISCUSSION AND CONCLUSION: Bariatric surgery improves obstetric and neonatal prognosis. Improvements have to be developed in the multidisciplinary follow-up in order to avoid nutritional deficiencies or important weight gain pregnancy in case of GB.

Long-term metabolic outcome and quality of life after laparoscopic adjustable gastric banding in obese patients with type 2 diabetes mellitus or impaired fasting glucose.

BACKGROUND: The long-term outcome of type 2 diabetes mellitus after laparoscopic adjustable gastric banding (LAGB) is unknown. METHODS: A longitudinal cohort study was undertaken of patients with grade 3 obesity and type 2 diabetes or impaired fasting glucose (IFG) undergoing LAGB. Metabolic outcomes and quality of life (QoL) were assessed before and 5 years after LAGB. RESULTS: At 5 years, data for 22 out of 23 patients with type 2 diabetes and 51 out of 53 with IFG were available. Mean(s.d.) excess weight loss was 41(25) and 41(27) per cent in patients with type 2 diabetes and IFG respectively, and was associated with a significant decrease in haemoglobin (Hb) A1c, fasting and postprandial blood glucose, insulin and triglyceride levels, and in liver steatosis. There were significant increases in insulin sensitivity, beta-cell function, disposition index, high-density lipoprotein-cholesterol and QoL (Nottingham Health Profile). Good metabolic control (HbA1c 7 per cent or less) was obtained in 13 diabetic patients, but complete diabetes remission was maintained in only four. Longer duration of diabetes, and poor preoperative glucose control and beta-cell function at baseline were associated with a less favourable outcome. CONCLUSION: LAGB improved metabolic outcomes and QoL in patients with grade 3 obesity with IFG or type 2 diabetes but rarely led to prolonged remission in long-standing diabetes.

Influence of maternal educational level on the association between the rs3809508 neuromedin B gene polymorphism and the risk of obesity in the HELENA study.

OBJECTIVE: Neuromedin B (NMB) is a bombesin-like peptide, which inhibits food intake and modulates stress-related behaviour. An NMB gene polymorphism (P73T) has been earlier associated with obesity and abnormal eating behaviour in adults. METHODS: The association between four NMB polymorphisms and obesity-related phenotypes was investigated in the Healthy Lifestyle in Europe by Nutrition in Adolescence cross-sectional study (n=1144, 12-17-year-old European adolescents). This population was genotyped for the NMB rs1107179, rs17598561, rs3809508 and rs1051168 (P73T) polymorphisms. Obesity was defined according to Cole et al. (BMJ 2000; 320:1240-1243) criteria; eating behaviour was assessed by the Eating Behaviour and Weight Problems Inventory for Children (EWI-C) and the food choices and preferences questionnaires. Familial socioeconomic status (SES) was assessed through the parents' educational level. RESULTS: Only the genotype distribution of rs3809508 differed according to obesity status, as the TT genotype was more frequent in obese than in non-obese adolescents (8.6% vs 3.1%, P=0.05; adjusted odds ratio for obesity (95% confidence interval): 2.85 (1.11-7.31), P=0.03). Moreover, TT subjects had higher body mass index (22.8+/-4.4 kg m(-2) vs 21.3+/-3.7 kg m(-2), P=0.02), waist circumference (75.8+/-9.7 cm vs 72.2+/-9.3 cm, P=0.006), waist-to-hip ratio (0.84+/-0.14 vs 0.79+/-0.07, P<0.0001) and waist-to-height ratio (0.47+/-0.06 vs 0.44+/-0.55, P=0.002) than C allele carriers. The effects of this single nucleotide polymorphism on all anthropometric values were influenced by the maternal SES, in that a low maternal educational level aggravated the phenotype of adolescents carrying the TT genotype (interactions: P<0.02). No association with EWI-C scores was found, although sweet craving was a more frequent cause of between-meal food intake in TT subjects than in C allele carriers (24.3% vs 9.2%, P=0.01). CONCLUSION: In European adolescents, the TT genotype of the NMB rs3809508 polymorphism was associated with a higher risk of obesity. Moreover, the effects of this polymorphism on anthropometric values were influenced by the maternal educational level.

Common genetic variation near MC4R is associated with eating behaviour patterns in European populations.

Both rs17782313 (near MC4R) and rs1421085 (FTO) polymorphisms have been consistently associated with increased risk of obesity and with body mass index (BMI) variation. An effect of both polymorphisms on satiety has recently been suggested. We genotyped rs17782313 and rs1421085 in 5764 relatives from 1109 French pedigrees with familial obesity, 1274 Swiss class III obese adults as well as in 4877 French adults and 5612 Finnish teenagers from two randomly selected population cohorts. In all subjects, eating behaviour traits were documented through questionnaires. We first assessed the association of both single nucleotide polymorphisms with BMI and then studied eating behaviour. Under an additive model, the rs17782313-C MC4R allele showed a trend towards higher percentages of snacking in both French obese children (P=0.01) and Swiss obese adults (P=0.04) as well as in adolescents from the Finnish general population (P=0.04). In French adults with familial obesity, this allele tended to be also associated with a higher Stunkard hunger score (P=0.02) and in obese children with a higher prevalence of eating large amounts of food (P=0.04). However, no consistent association of the FTO rs1421085-C allele and available eating behaviour trait was found in our studied populations. The rs17782313-C allele nearby MC4R may modulate eating behaviour-related phenotypes in European obese and randomly selected populations, in both children and adults, supporting a regulatory role of this genetic variant on eating behaviour, as previously shown for MC4R non-synonymous loss-of-function mutations. The potential effect of the obesity-associated FTO gene on eating behaviour deserves additional investigation.

Laparoscopic gastric bypass complicated by portal venous thrombosis and severe neurological complications.

The laparoscopic Roux-en-Y gastric bypass (LRYGBP) is increasingly popular for the treatment of morbid obesity, although its postsurgical complications are often underestimated. We report the case of a 22-year-old morbidly obese woman who underwent a LRYGBP, which was rapidly complicated by portal venous thrombosis and severe neurological complications due to vitamin deficiencies. She presented rapid body weight loss with optic and peripheral neuropathy. Clinical chemistry results showed low transthyretin and micronutrient levels. Intravenous micronutrient infusion and cyclic nocturnal enteral tube feeding were needed to slowly improve gait and visual acuity. We then discuss (1) factors that could have contributed to the nutritional deficiencies and (2) the preventive management of these types of nutritional complications. Gastric bypass procedures can cause multivitamin deficiencies. In the case presented here, complications occurred very soon after surgery. The increasing incidence of obesity and bariatric surgery warrants better patient education concerning strict adherence to vitamin supplementation.

Beneficial effects of propylthiouracil plus L-thyroxine treatment in a patient with a mutation in MCT8.

CONTEXT: Mutations of the monocarboxylate transporter 8 (MCT8) gene determine a distinct X-linked phenotype of severe psychomotor retardation and consistently elevated T(3) levels. Lack of MCT8 transport of T(3) in neurons could explain the neurological phenotype. OBJECTIVE: Our objective was to determine whether the high T(3) levels could also contribute to some critical features observed in these patients. RESULTS: A 16-yr-old boy with severe psychomotor retardation and hypotonia was hospitalized for malnutrition (body weight = 25 kg) and delayed puberty. He had tachycardia (104 beats/min), high SHBG level (261 nmol/liter), and elevated serum free T(3) (FT(3)) level (11.3 pmol/liter), without FT(4) and TSH abnormalities. A missense mutation of the MCT8 gene was present. Oral overfeeding was unsuccessful. The therapeutic effect of propylthiouracil (PTU) and then PTU plus levothyroxine (LT(4)) was tested. After PTU (200 mg/d), serum FT(4) was undetectable, FT(3) was reduced (3.1 pmol/liter) with high TSH levels (50.1 mU/liter). Serum SHBG levels were reduced (72 nmol/liter). While PTU prescription was continued, high LT(4) doses (100 microg/d) were needed to normalize serum TSH levels (3.18 mU/liter). At that time, serum FT(4) was normal (16.4 pmol/liter), and FT(3) was slightly high (6.6 pmol/liter). Tachycardia was abated (84 beats/min), weight gain was 3 kg in 1 yr, and SHBG was 102 nmol/liter. CONCLUSIONS: 1) When thyroid hormone production was reduced by PTU, high doses of LT(4) (3.7 microg/kg.d) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone. 2) High T(3) levels might exhibit some deleterious effects on adipose, hepatic, and cardiac levels. 3) PTU plus LT(4) could be an effective therapy to reduce general adverse features, unfortunately without benefit on the psychomotor retardation.

[Genetic obesities]. / Obésités génétiques.

Obesity has become an increasingly prevalent public health problem and results of the complex interaction of genetic and environmental factors. The study of rare syndromic forms of obesity enables progress in identifying molecular and physiological mechanisms, underlying the development of adiposity, food intake and energy expenditure. The identified role of the hypothalamic leptin-melanocortin pathway as major in monogenic forms of obesity, has led to the recognition of new genes controlling energy homeostasis and new pharmacological targets.

Effect of weight loss on the postprandial response to high-fat and high-carbohydrate meals in obese women.

OBJECTIVE: To assess the effect of weight loss on the plasma lipid and remnant-like lipoprotein cholesterol (RLPc) response to a high-fat or a high-carbohydrate meal in a population of obese women. DESIGN: Nutritional intervention study. SUBJECTS: Sixteen obese women (mean body mass index (BMI): 37.6+/-5 kg/m(2)). METHODS: Subjects were asked to follow an energy-restricted diet (800 kcal/day) for 7 weeks, followed by a 1-week maintenance diet. Before and after weight loss, each participant was given (in random order) two iso-energetic meals containing either 80% fat and 20% protein (the high-fat meal) or 80% carbohydrate and 20% protein (the high-carbohydrate meal). Blood samples were collected over the following 10-h period. A two-way analysis of variance with repeated measures was used to assess the effect of the meal and postprandial time on biological variables and postprandial responses (notably RLPc levels). RESULTS: Weight loss was associated with a significant decrease in fasting triglyceride (P=0.0102), cholesterol (P<0.0001), low-density lipoprotein cholesterol (P=0.0003), high-density lipoprotein-cholesterol (P=0.0009) and RLPc (P=0.0015) levels. The triglyceride response to the high-fat meal was less intense after weight reduction than before (interaction P<0.002). This effect persisted after adjustment on baseline triglyceride levels. The triglyceride response to the high-carbohydrate meal was biphasic (i.e. with two peaks, 1 and 6 h after carbohydrate intake). After adjustment on baseline values, weight reduction was associated with a trend towards a reduction in the magnitude of the second triglyceride peak (interaction P<0.054). In contrast, there was no difference in postprandial RLPc responses before and after weight loss, again after adjustment on baseline levels. CONCLUSION: Our data suggest that weight loss preferentially affects postprandial triglyceride metabolism.