Locally implemented prevention programs may reverse weight trajectories in half of children with overweight/obesity amid low child-staff ratios: results from a quasi-experimental study in France.

BACKGROUND: The aims of the present study were to assess changes in weight status between the first and last year of primary education among children with overweight/obesity in response to locally implemented school-based prevention programs, and to assess the influence of process indicators, expressed as child-staff ratios (CSRs), on these changes. METHODS: To meet the study objectives, a quasi-experimental design was used. Four municipalities that systematically monitored the weight status of schoolchildren and participated in the "Vivons en Forme" program agreed to provide the data available in their school medical service records. The local implementers involved in training sessions were mainly municipal staff in charge of serving midday school meals, which is compulsory in France, and those in charge of designing and facilitating creative, interactive activities at school between and after classes. CSRs were determined by occupation (school catering service/facilitator of extracurricular activities) and training session (healthy eating/physical activity) in each municipality program, and classified as low (1-5 children per adult) or moderate. RESULTS: During the 4 years of primary education, weight status improved in half of the children with overweight/obesity, and worsened in 6.6% of children with overweight/normal weight. In children who remained overweight, the BMI z-score diminished over time. Estimates of the positive 4-year weight changes were related to low CSRs in locally implemented variations of the program. Estimates increased with age and were significantly higher in low-to-moderate CSR multicomponent interventions than moderate CSR single-component intervention (reference). The moderate CSR multicomponent intervention had a similar effect as the reference. The estimated negative weight change decreased with age. CONCLUSIONS: Our findings suggest that training ancillary school staff in experiential-focused interventions for healthy eating and physical activity in locally implemented school-based programs contributed positively to reducing childhood obesity during the four years of primary education without interfering with educational activities. The results also provide preliminary evidence that low CSRs could be pivotal for optimal outcomes, especially in deprived areas.

Positional candidate gene analysis of Lim domain homeobox gene (Isl-1) on chromosome 5q11-q13 in a French morbidly obese population suggests indication for association with type 2 diabetes.

The Lim domain homeobox gene (Isl-1) is a positional candidate gene for obesity that maps on chromosome 5q11-q13, a locus linked to BMI and leptin levels in French Caucasians. Isl-1 might be involved in body weight regulation and glucose homeostasis via the activation of proglucagon gene expression, which encodes for glucagon and glucagon-like peptides. By mutation screening of 72 obese subjects, we identified three single-nucleotide polymorphisms (SNPs) in the Isl1 gene. The allele frequencies in the morbidly obese group did not differ from that of the control group. In the obese group, the -47G allele was associated with a decreased risk of type 2 diabetes (odds ratio 0.41, P = 0.019). The AG bearers displayed a higher maximal BMI than the AA bearers in the whole obese group (P = 0.026) as well as in the type 2 diabetic obese subgroup (P = 0.014). In obese families, this allele was not preferentially transmitted from heterozygous parents to their obese siblings, indicating that Isl-1 does not contribute to the linkage with obesity on 5cen-q. However, in French Caucasian morbidly obese subjects, the Isl1-47A-->G SNP may modulate the risk for type 2 diabetes and may increase body weight in diabetic morbidly obese subjects.

Genome-wide linkage analysis for severe obesity in french caucasians finds significant susceptibility locus on chromosome 19q.

To ascertain whether distinct chromosomal loci existed that were linked to severe obesity, as well as to utilize the increased heritability of this excessive phenotype, we performed a genome-wide scan in severely obese French Caucasians. The 109 selected pedigrees, totaling 447 individuals, required both the proband and a sibling to be severely obese (BMI >or=35 kg/m(2)), and 84.8% of the nuclear families possessed >or=1 morbidly obese sibling (BMI >or=40). Severe and morbid obesity are still relatively rare in France, with rates of 2.5 and 0.6%, respectively. The initial genome scan consisted of 395 evenly spaced microsatellite markers. Six regions were found to have suggestive linkage on 4q, 6cen-q, 17q, and 19q for a BMI >or=35 phenotypic subset, and 5q and 10q for an inclusive BMI >or=27 group. The highest peak on chromosome 19q (logarithm of odds [LOD] = 3.59) was significant by genome scan simulation testing (P = 0.042). These regions then underwent second-stage mapping with an additional set of 42 markers. BMI >or=35 analysis defined regions on 17q23.3-25.1 and 19q13.33-13.43 with an maximum likelihood score LOD of 3.16 and 3.21, respectively. Subsequent pooled data analysis with an additional previous population of 66 BMI >or=35 sib-pairs led to a significant LOD score of 3.8 at the 19q locus (empirical P = 0.023). For more moderate obesity and overweight susceptibility loci, BMI >or=27 analysis confirmed suggestive linkage to chromosome regions 5q14.3-q21.3 (LOD = 2.68) and 10q24.32-26.2 (LOD = 2.47). Plausible positional candidate genes include NR1H2 and TULP2.

One-year changes in energy expenditure and serum leptin following adjustable gastric banding in obese women.

BACKGROUND: Weight loss is associated with a decrease in both energy expenditure and circulating leptin levels. Whether this holds true when the influence of body composition on energy expenditure and leptin is taken into account remains controversial. The aim of the study was to assess changes in resting metabolic rate (RMR) and serum leptin adjusted for body composition during surgically induced weight loss. METHODS: In 36 women (age 42.7+/-8.7 years; BMI 47.2+/-8.5 kg/m(2); mean+/-SD) undergoing laparoscopic adjustable gastric banding (LAGB) for morbid obesity, we measured RMR (by indirect calorimetry), body composition (by dual-energy X-ray absorptiometry) and serum leptin (by immunoradiometry), immediately before and 1 year after surgery. RESULTS: 1 year after LAGB, there were significant decreases in body weight (-23.7+/-11.6 kg, P<0.001), fat mass (FM: -20.9+/-11.3 kg, P<0.0001), lean body mass (LBM: -3+/-5.3 kg, P=0.005), RMR (-298+/-309 kcal/day, P<0.0001), serum leptin (-24.0+/-18.4 ng/ml, P<0.0001), RMR/LBM ratio (-3.9+/-5.8 kcal/kg LBM/day, P<0.01) and leptin/FM ratio (-0.21+/-0.29 ng/kg FM/ml, P<0.001). RMR values after surgery were correctly predicted by the regression equation relating RMR to LBM and FM at baseline, whereas this was not the case for serum leptin (in relation to FM). CONCLUSIONS: Changes in RMR 1 year after LAGB were explained by changes in body composition whereas changes in serum leptin were not. The data provide no evidence for a metabolic adaptation of RMR with weight loss, but suggest that serum leptin is decreased beyond expected values based on body composition, a factor that may favor weight regain after surgically induced weight loss.

Comparison of two physical activity questionnaires in obese subjects: the NUGENOB study.

PURPOSE: Simple instruments are needed to assess habitual physical activity (PA) in obese subjects. In a multicenter European obesity project, we tested whether PA assessments by two questionnaires were correlated and similarly associated to selected obesity-related variables. METHODS: A total of 757 obese subjects (75% female; age 37.1 [7.9] yr, BMI 35.5 [4.9] kg.m(-2), mean [SD]) completed the Baecke questionnaire (assessing work, sport, and nonsport leisure activity) and the short last 7-d version of the International Physical Activity Questionnaire (IPAQ; assessing vigorous, moderate-intensity, walking activity, and sitting). We assessed percent body fat (bioimpedance), waist circumference, and fasting plasma concentrations of glucose, insulin, leptin, and FFA. Insulin sensitivity was assessed by the HOMA index for insulin resistance (HOMAIR). RESULTS: Using the IPAQ, only about one third of men and women were classified as insufficiently active. Total habitual PA assessments by the Baecke and IPAQ were significantly related (Spearman rho = 0.51 in total sample, P < or = 0.0001, with adjustment for age, gender, and center). Using principal component analysis, we built two uncorrelated indices corresponding to general obesity (determined by high body fat and leptin) and abdominal obesity (determined by high waist circumference and HOMAIR). PA scores from both questionnaires were negatively related to general and abdominal obesity indices, except for abdominal obesity with the IPAQ in men. CONCLUSIONS: Total PA assessments by the two questionnaires were found to correlate significantly, and the general pattern of associations of PA with general obesity was similar for the two questionnaires. However, the IPAQ may capture less of the relationships between PA and abdominal obesity than the Baecke, especially in men. Reporting of habitual PA in obese subjects with the IPAQ warrants further evaluation against objective assessment methods.

Adiponectin gene expression in subcutaneous adipose tissue of obese women in response to short-term very low calorie diet and refeeding.

Adiponectin is an adipocyte-derived protein suggested to be involved in energy homeostasis and in lipid and glucose metabolism. Little is known regarding the consequence of acute changes in energy balance on adiponectin mRNA expression in human adipose tissue. Using a real-time RT-PCR assay, we investigated the effects of 2-d very low calorie diet (VLCD) and subsequent refeeding on adiponectin mRNA expression in sc adipose tissue of morbidly obese women. Basal adiponectin mRNA abundance of the obese women showed a wide distribution (2.6-14.3 mRNA/18S rRNA; coefficient of variation, 51.2%) and was significantly lower than that of lean controls (P < 0.001). In the obese group, the VLCD caused a 33% rise (P < 0.01) in the average level of mRNA, whereas refeeding caused a 32.8% fall (P < 0.05). In contrast, the change in leptin mRNA expression with either VLCD or refeeding was not statistically significant. The obese subjects who showed an acute adiponectin mRNA response to the changes in energy intake had a higher basal level of adiponectin mRNA (P = 0.02) and a borderline-significantly lower body mass index compared with the subjects who showed no or weak adiponectin mRNA response. Insulin sensitivity of the responder subgroup significantly increased by 89% (P = 0.008) after the VLCD, whereas insulin sensitivity of the nonresponder subgroup only increased by 24% (P = 1.56). This study indicates that adiponectin mRNA in sc adipose tissue can acutely respond to short-term energy changes in some obese subjects. Both the levels of adiposity and insulin sensitivity may contribute to the variation in adiponectin gene expression in response to acute energy changes.

Anthropometric estimates of muscle and fat mass in relation to cardiac and cancer mortality in men: the Paris Prospective Study.

BACKGROUND: The associations of different components of body mass with disease outcomes are not well defined. OBJECTIVE: We investigated the effects of body composition on risk of death from cardiac causes and cancer in adult men. DESIGN: Middle-aged men (n = 7608) in the Paris Prospective Study were followed up for 15 y. At study entry, the following measurements were obtained: sagittal diameter, sum of midarm and midthigh circumferences, sum of 3 trunk skinfold thicknesses (estimate of trunk subcutaneous fat), and sum of 3 extremity skinfold thicknesses (estimate of extremity subcutaneous fat). To assess their relative contributions to cardiac and cancer mortality, we used multivariate Cox models in which the sagittal diameter adjusted for trunk skinfold thicknesses was used as an estimate of intraabdominal fat and the sum of midarm and midthigh circumferences adjusted for extremity skinfold thicknesses was used as an estimate of muscle mass. RESULTS: In multivariate analyses in both smokers and nonsmokers, the sagittal diameter was the only significant predictor of cardiac death. The sum of midarm and midthigh circumferences was negatively associated and sagittal diameter was positively associated with cancer death, whereas extremity skinfold thicknesses exhibited a U-shape relation. Exclusion of subjects who died from cancer in the first 5 y of follow-up did not change these results. CONCLUSIONS: Intraabdominal fat appears to be the main body compartment involved in risk of cardiac death, whereas increased risk of cancer death is associated with lower muscle mass and lower subcutaneous fat, independent of smoking and after the exclusion of early mortality. Increased central fat distribution may confer additional risk of death from cancer.

Topiramate: long-term maintenance of weight loss induced by a low-calorie diet in obese subjects.

OBJECTIVE: To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low-calorie diet. RESEARCH METHODS AND PROCEDURES: Obese subjects (30 < or = BMI < 50 kg/m(2)) 18 to 75 years old received a low-calorie diet for 8 weeks. Those who lost > or =8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled-release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination. RESULTS: Of the 701 subjects enrolled, 80% lost > or =8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run-in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system. DISCUSSION: During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low-calorie diet-and produced additional clinically significant weight loss beyond that achieved by a low-calorie diet.

Lipoprotein oxidation and plasma vitamin E in nondiabetic normotensive obese patients.

OBJECTIVE: To correlate the susceptibility of low-(LDL) and very-low-density lipoprotein to oxidation in vitro and the concentrations of serum antibodies against malondialdehyde-modified LDL and plasma vitamin E with the anthropometric and laboratory characteristics of obesity. RESEARCH METHODS AND PROCEDURES: A total of 75 nondiabetic, normotensive obese patients were assigned to one of four groups according to their body mass index (BMI): moderately obese (30 50 kg/m(2), n = 15). RESULTS: The oxidation lag time for LDL from patients with a BMI >or=35 kg/m(2) was shorter than that for LDL from non-obese controls (n = 13), whereas very-low-density lipoprotein oxidation lag times were not significantly different. The serum antibodies against modified LDL were similar in all groups, whereas the plasma vitamin E concentrations of obese patients were decreased (p

Adipose angiotensinogen secretion, blood pressure, and AGT M235T polymorphism in obese patients.

OBJECTIVE: To investigate AGT secretion in cultured adipocytes from obese patients and its relationship with obesity-related phenotypes, blood pressure, and the M235T polymorphism in the AGT gene. RESEARCH METHODS AND PROCEDURES: Measurements, including anthropometry, body composition (DXA), and blood pressure, were performed in 61 overweight or obese women (BMI: 28 to 68 kg/m(2)). A subcutaneous abdominal adipose tissue biopsy was used for adipocyte size determination and quantification of AGT secretion in the medium of cultured adipocytes. AGT M235T genotype was determined using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Adipose secretion of the AGT protein (range, 140 to 2575 ng/10(6) cells/24 h) was not significantly correlated with BMI, body fat, or blood pressure and did not vary according to the M235T polymorphism in the AGT gene. However, the AGT M235T polymorphism was associated with adipocyte size (111.6 +/- 2.8, 108.8 +/- 1.9, 118.2 +/- 2.6 micro m in MM, MT, and TT genotypes, respectively; p < 0.01) after adjustment for age and fat mass. An association between the AGT M235T polymorphism and adipocyte size (p < 0.02 adjusted for sex, age, and BMI) was found in another independent sample of 106 obese subjects (sex ratio, M/F 16/90; BMI, 29 to 70 kg/m(2)). DISCUSSION: In cultured adipocytes from obese subjects, AGT secretion was not associated with body fat phenotypes, blood pressure, or fat cell size. However, results from two independent studies suggest an association between the AGT M235T polymorphism and adipocyte size.

The Eating Inventory and body adiposity from leanness to massive obesity: a study of 2509 adults.

OBJECTIVE: To examine how chronic dietary restraint, disinhibition, and hunger, as assessed by the Eating Inventory, vary over a broad range of BMI values from leanness to massive obesity, in subjects with family obesity. Eating Inventory factors were also studied as a function of personal weight history. RESEARCH METHODS AND PROCEDURES: Subjects were 2509 participants in a genetic study of obesity. BMIs ranged from 15 to 87 kg/m2. Six BMI groups were formed (<27, 27 to 30, 30 to 35, 35 to 40, 40 to 45, and >45). RESULTS: Multivariate analyses showed that restraint and disinhibition were significantly associated with BMI in men, whereas only disinhibition was in women. Disinhibition scores correlated strongly with hunger scores in both genders in all BMI categories; dietary restraint tended to correlate with the other two factors positively in leaner subjects and negatively in the highest BMI categories. Highly restrained normal-weight subjects were likely to exhibit disinhibition and hunger, whereas massively obese persons with very high disinhibition scores showed high hunger but little restraint. The highest restraint scores were observed in nonobese adult women with previous obesity in childhood and/or adolescence. DISCUSSION: The factor most strongly associated with BMI in this large population was disinhibition, suggesting that obesity treatment should target behaviors associated with disinhibition, especially in individuals showing a low level of dietary restraint. High restraint scores in formerly obese normal-weight women suggest that dietary restraint may exert a beneficial influence on body weight control under conditions that deserve further investigation.

Role of the DGAT gene C79T single-nucleotide polymorphism in French obese subjects.

Acyl-coenzyme A, diacylglycerol acyltransferase (DGAT), is a key enzyme involved in adipose-cell triglyceride storage. A 79-bp T-to-C single-nucleotide polymorphism (SNP) on the 3' region of the DGAT transcriptional site has been reported to increase promoter activity and is associated with higher BMI in Turkish women. To validate the possible role of this genetic variant in obesity, as well as the variant's possible cellular-functional significance, we performed an association study between the T79C change and several obesity-related phenotypes in 1357 obese French adults and children. The prevalence of the T79C SNP was similar between obese adults and children when each group was compared with the controls. (CC genotype carrier frequencies were 0.25 to 0.29 in the obese groups and 0.21 in controls; p > 0.05.) In each of the obese adult and child groups studied, the T79C variant was not found to be associated with any of the obesity-related phenotypes tested. Although the T79C SNP of the DGAT gene was studied in several groups of white subjects, the association between this SNP and obesity-related phenotypes, previously described, was not confirmed in our population.