Pathogenic variants in actionable MODY genes are associated with type 2 diabetes.

Genome-wide association studies have identified 240 independent loci associated with type 2 diabetes (T2D) risk, but this knowledge has not advanced precision medicine. In contrast, the genetic diagnosis of monogenic forms of diabetes (including maturity-onset diabetes of the young (MODY)) are textbook cases of genomic medicine. Recent studies trying to bridge the gap between monogenic diabetes and T2D have been inconclusive. Here, we show a significant burden of pathogenic variants in genes linked with monogenic diabetes among people with common T2D, particularly in actionable MODY genes, thus implying that there should be a substantial change in care for carriers with T2D. We show that, among 74,629 individuals, this burden is probably driven by the pathogenic variants found in GCK, and to a lesser extent in HNF4A, KCNJ11, HNF1B and ABCC8. The carriers with T2D are leaner, which evidences a functional metabolic effect of these mutations. Pathogenic variants in actionable MODY genes are more frequent than was previously expected in common T2D. These results open avenues for future interventions assessing the clinical interest of these pathogenic mutations in precision medicine.

Loss-of-function mutations in MRAP2 are pathogenic in hyperphagic obesity with hyperglycemia and hypertension.

The G-protein-coupled receptor accessory protein MRAP2 is implicated in energy control in rodents, notably via the melanocortin-4 receptor1. Although some MRAP2 mutations have been described in people with obesity1-3, their functional consequences on adiposity remain elusive. Using large-scale sequencing of MRAP2 in 9,418 people, we identified 23 rare heterozygous variants associated with increased obesity risk in both adults and children. Functional assessment of each variant shows that loss-of-function MRAP2 variants are pathogenic for monogenic hyperphagic obesity, hyperglycemia and hypertension. This contrasts with other monogenic forms of obesity characterized by excessive hunger, including melanocortin-4 receptor deficiency, that present with low blood pressure and normal glucose tolerance4. The pleiotropic metabolic effect of loss-of-function mutations in MRAP2 might be due to the failure of different MRAP2-regulated G-protein-coupled receptors in various tissues including pancreatic islets.

Nutriepigenomics and malnutrition.

Epigenetics is defined as the modulation of gene expression without changes to the underlying DNA sequence. Epigenetic alterations, as a consequence of in utero malnutrition, may play a role in susceptibility to develop adulthood diseases and inheritance. However, the mechanistic link between epigenetic modifications and abnormalities in nutrition remains elusive. This review provides an update on the association of suboptimal nutritional environment and the high propensity to produce adult-onset chronic illnesses with a particular focus on modifications in genome functions that occur without alterations to the DNA sequence. We will mention the drivers of the phenotype and pattern of epigenetic markers set down during the reprogramming along with novel preventative and therapeutic strategies. New knowledge of epigenetic alterations is opening a gate toward personalized medicine.

The Epigenetic Machinery in Vascular Dysfunction and Hypertension.

Hypertension (HT) is among the major components of the metabolic syndrome, i.e., obesity, dyslipidemia, and hyperglycemia/insulin resistance. It represents a significant health problem with foremost risks for chronic cardiovascular disease and a significant cause of morbidity and mortality worldwide. Therefore, it is not surprising that this disorder constitutes a serious public health concern. Although multiple studies have stressed the multifactorial nature of HT, the pathogenesis remains largely unknown. However, if we want to reduce the global prevalence of HT, restrain the number of deaths (currently 9.4 million/year in the world), and alleviate the socio-economic burden, a deeper insight into the mechanisms is urgently needed in order to define new meaningful therapeutic targets. Recently, the role of epigenetics in the development of various complex diseases has attracted much attention. In the present review, we provide a critical update on the available literature and ongoing research regarding the epigenetic modifications of genes involved in several pathways of elevated blood pressure, especially those linked to the vascular epithelium. This review also focuses on the role of microRNA (miRNA) in the regulation of gene expression associated with HT and of fetal programming mediating susceptibility to HT in adulthood.

Relationship between salivary/pancreatic amylase and body mass index: a systems biology approach.

BACKGROUND: Salivary (AMY1) and pancreatic (AMY2) amylases hydrolyze starch. Copy number of AMY1A (encoding AMY1) was reported to be higher in populations with a high-starch diet and reduced in obese people. These results based on quantitative PCR have been challenged recently. We aimed to re-assess the relationship between amylase and adiposity using a systems biology approach. METHODS: We assessed the association between plasma enzymatic activity of AMY1 or AMY2, and several metabolic traits in almost 4000 French individuals from D.E.S.I.R. longitudinal study. The effect of the number of copies of AMY1A (encoding AMY1) or AMY2A (encoding AMY2) measured through droplet digital PCR was then analyzed on the same parameters in the same study. A Mendelian randomization analysis was also performed. We subsequently assessed the association between AMY1A copy number and obesity risk in two case-control studies (5000 samples in total). Finally, we assessed the association between body mass index (BMI)-related plasma metabolites and AMY1 or AMY2 activity. RESULTS: We evidenced strong associations between AMY1 or AMY2 activity and lower BMI. However, we found a modest contribution of AMY1A copy number to lower BMI. Mendelian randomization identified a causal negative effect of BMI on AMY1 and AMY2 activities. Yet, we also found a significant negative contribution of AMY1 activity at baseline to the change in BMI during the 9-year follow-up, and a significant contribution of AMY1A copy number to lower obesity risk in children, suggesting a bidirectional relationship between AMY1 activity and adiposity. Metabonomics identified a BMI-independent association between AMY1 activity and lactate, a product of complex carbohydrate fermentation. CONCLUSIONS: These findings provide new insights into the involvement of amylase in adiposity and starch metabolism.

Metabolic Syndrome as a Multifaceted Risk Factor for Oxidative Stress.

SIGNIFICANCE: Metabolic syndrome (MetS) is associated with a greater risk of diabetes and cardiovascular diseases. It is estimated that this multifactorial condition affects 20%-30% of the world's population. A detailed understanding of MetS mechanisms is crucial for the development of effective prevention strategies and adequate intervention tools that could curb its increasing prevalence and limit its comorbidities, particularly in younger age groups. With advances in basic redox biology, oxidative stress (OxS) involvement in the complex pathophysiology of MetS has become widely accepted. Nevertheless, its clear association with and causative effects on MetS require further elucidation. Recent Advances: Although a better understanding of the causes, risks, and effects of MetS is essential, studies suggest that oxidant/antioxidant imbalance is a key contributor to this condition. OxS is now understood to be a major underlying mechanism for mitochondrial dysfunction, ectopic lipid accumulation, and gut microbiota impairment. CRITICAL ISSUES: Further studies, particularly in the field of translational research, are clearly required to understand and control the production of reactive oxygen species (ROS) levels, especially in the mitochondria, since the various therapeutic trials conducted to date have not targeted this major ROS-generating system, aimed to delay MetS onset, or prevent its progression. FUTURE DIRECTIONS: Multiple relevant markers need to be identified to clarify the role of ROS in the etiology of MetS. Future clinical trials should provide important proof of concept for the effectiveness of antioxidants as useful therapeutic approaches to simultaneously counteract mitochondrial OxS, alleviate MetS symptoms, and prevent complications. Antioxid. Redox Signal. 26, 445-461.

Oxidative Stress as a Critical Factor in Nonalcoholic Fatty Liver Disease Pathogenesis.

SIGNIFICANCE: Nonalcoholic fatty liver disease (NAFLD), characterized by liver triacylglycerol build-up, has been growing in the global world in concert with the raised prevalence of cardiometabolic disorders, including obesity, diabetes, and hyperlipemia. Redox imbalance has been suggested to be highly relevant to NAFLD pathogenesis. Recent Advances: As a major health problem, NAFLD progresses to the more severe nonalcoholic steatohepatitis (NASH) condition and predisposes susceptible individuals to liver and cardiovascular disease. Although NAFLD represents the predominant cause of chronic liver disorders, the mechanisms of its development and progression remain incompletely understood, even if various scientific groups ascribed them to the occurrence of insulin resistance, dyslipidemia, inflammation, and apoptosis. Nevertheless, oxidative stress (OxS) more and more appears as the most important pathological event during NAFLD development and the hallmark between simple steatosis and NASH manifestation. CRITICAL ISSUES: The purpose of this article is to summarize recent developments in the understanding of NAFLD, essentially focusing on OxS as a major pathogenetic mechanism. Various attempts to translate reactive oxygen species (ROS) scavenging by antioxidants into experimental and clinical studies have yielded mostly encouraging results. FUTURE DIRECTIONS: Although augmented concentrations of ROS and faulty antioxidant defense have been associated to NAFLD and related complications, mechanisms of action and proofs of principle should be highlighted to support the causative role of OxS and to translate its concept into the clinic. Antioxid. Redox Signal. 26, 519-541.

Inequalities in energy-balance related behaviours and family environmental determinants in European children: changes and sustainability within the EPHE evaluation study.

BACKGROUND: Increasing social inequalities in health across Europe are widening the gap between low and high socio-economic groups, notably in the prevalence of obesity. Public health interventions may result in differential effects across population groups. Therefore, the EPHE (EPODE for the Promotion of Health Equity) project analysed the added value of community-based programmes, based on the EPODE (Ensemble Prévenons l'Obésité Des Enfants-Together Let's Prevent Obesity) model, to reduce socio-economic inequalities in energy balance-related behaviours of children and their family-environmental related determinants in seven European communities. This study presents the changes between baseline and follow-up after the one-year interventions and their sustainability one year after. METHODS: This is a prospective study with a one school-year intervention, followed by one year of follow-up. In all, 1266 children (age 6-8 years) and their families from different socio-economic backgrounds were recruited at baseline. For 1062 children, information was available after one year (T1) and for 921 children after two years (T2). A self-reported questionnaire was completed by the parents to examine the children's energy balance-related behaviours and family- environmental determinants. Socio-economic status was defined by the educational level of the mother. The Wilcoxon signed-rank test for paired data was used to test the differences between baseline and intermediate, and between intermediate and final, measurements for each of the socio-economic status groups. RESULTS: Post-intervention effects in energy-balance related behaviours showed the following improvements among the low socio-economic status groups: increased fruit consumption (Netherlands), decreased fruit juices amount consumed (Romania) and decreased TV time on weekdays (Belgium). Whereas in only the latter case the behavioural change was accompanied with an improvement in a family-environmental determinant (monitoring the time the child watches TV), other improvements in parental rules and practices related to soft drinks/fruit juices and TV exposure were observed. A few of those effects were sustainable, notably in the case of Belgium. CONCLUSIONS: Inequalities in obesity-related behaviours could be potentially reduced when implementing community-based interventions, tailored to inequality gaps and using the EPODE methodology. Within-group changes varied widely, whereas monitoring of interventions and process evaluation are crucial to understand the observed results.

Tackling Health Inequities and Reducing Obesity Prevalence: The EPODE Community-Based Approach.

BACKGROUND: Tackling inequalities in overweight, obesity and related complications has become a top priority for European research and policy agendas. It is well-known that the health message often does not reach disadvantaged populations, a phenomenon that widens health inequalities. Ensemble Prévenons l'Obésité des Enfants (EPODE) methodology is an innovative approach to counteract obesity and improve health equity. EPODE for the Promotion of Health Equity (EPHE) has assessed the impact and sustainability of the EPODE methodology to diminish inequalities in childhood obesity prevention. The current data represent the results of the intermediate measurements that were obtained following EPHE interventions in 7 European communities across different countries. METHODS: A total of 1,062 children aged 6-8 years and their parents from different socioeconomic backgrounds were observed for 2 years. A self-administrated questionnaire was sent to parents to measure the children's energy balance-related behaviors and their determinants. The Wilcoxon signed-rank test was used to test differences between baseline and intermediate measurements for each socioeconomic group. RESULTS: We observed changes in behaviors (fruit and vegetable consumption, sugary sweetened beverage consumption, screen exposure) and their related determinants, within the low and high education groups, which were associated with identified inequity gaps at baseline. Although statistical significance was not reached in most of the cases, greater improvements in behaviors were evident within the low education groups. CONCLUSIONS: Our findings show that, after EPODE interventions, the low socioeconomic groups improved their behavior compared to the other socio-economic groups. This indicates that the EPODE methodology has the capacity not only to reduce obesity prevalence but also to decrease health inequities.

Inequities in energy-balance related behaviours and family environmental determinants in European children: baseline results of the prospective EPHE evaluation study.

BACKGROUND: Tackling inequalities in overweight, obesity and related determinants has become a top priority for the European research and policy agendas. Although it has been established that such inequalities accumulate from early childhood onward, they have not been studied extensively in children. The current article discusses the results of an explorative analysis for the identification of inequalities in behaviours and their determinants between groups with high and low socio-economic status. METHODS: This study is part of the Epode for the Promotion of Health Equity (EPHE) evaluation study, the overall aim of which is to assess the impact and sustainability of EPODE methodology to diminish inequalities in childhood obesity and overweight. Seven community-based programmes from different European countries (Belgium, Bulgaria, France, Greece, Portugal, Romania, The Netherlands) participate in the EPHE study. In each of the communities, children aged 6-8 years participated, resulting in a total sample of 1266 children and their families. A parental self-administrated questionnaire was disseminated in order to assess the socio-economic status of the household, selected energy balance-related behaviours (1. fruit and vegetable consumption; 2. soft drink/ fruit juices and water consumption; 3. screen time and 4. sleep duration) of the children and associated family environmental determinants. The Mann-Whitney U test and Pearson's chi-square test were used to test differences between the low and high education groups. The country-specific median was chosen as the cut-off point to determine the educational level, given the different average educational level in every country. RESULTS: Children with mothers of relatively high educational level consumed fruits and vegetables more frequently than their peers of low socio-economic status. The latter group of children had a higher intake of fruit juices and/or soft drinks and had higher screen time. Parental rules and home availability were consistently different between the two socio-economic groups in our study in all countries. However we did not find a common pattern for all behaviours and the variability across the countries was large. CONCLUSIONS: Our findings are indicative of socio-economic inequalities in our samples, although the variability across the countries was large. The effectiveness of interventions aimed at chancing parental rules and behaviour on health inequalities should be studied.

Process evaluation outcomes from a global child obesity prevention intervention.

BACKGROUND: While it is acknowledged that child obesity interventions should cover multiple ecological levels (downstream, midstream and upstream) to maximize their effectiveness, there is a lack of evaluation data to guide the development and implementation of such efforts. To commence addressing this knowledge gap, the present study provides process evaluation data relating to the experiences of groups implementing the EPODE approach to child obesity prevention in various locations around the world. The aim of this exploratory study was to investigate the barriers and facilitators to program implementation in program sites around the world to assist in developing strategies to enhance program outcomes. METHODS: An online survey that included open-ended questions was distributed to the 25 EPODE programs in operation at the time of the survey (May 2012). The survey items asked respondents to comment on those aspects of program implementation that they found challenging and to suggest areas for future improvement. Eighteen programs representing 14 countries responded to the request to participate in the survey, yielding a 72% response rate. The responses were analyzed via the constant comparative method using NVivo qualitative data analysis software. RESULTS: The main concerns of the various EPODE programs were their ability to secure ongoing funding and their access to evidence-based intervention methods and policy advice relating to relationships with third parties. These issues were in turn impacted by other factors, including (i) access to user-friendly information relating to the range of intervention strategies available and appropriate evaluation measures; (ii) assistance with building and maintaining stakeholder relationships; and (iii) assurance of the quality, independence, and transparency of policies and practices. CONCLUSIONS: The findings are facilitating the ongoing refinement of the EPODE approach. In particular, standardized and tailored information packages are being made available to advise program members of (i) the various evaluation methods and tools at their disposal and (ii) methods of acquiring private partner support. Overall, the study results relating to the types of issues encountered by program members are likely to be useful in guiding the future design and implementation of multi-level initiatives seeking to address other complex and intractable health-related problems.

Promoting health equity in European children: design and methodology of the prospective EPHE (Epode for the Promotion of Health Equity) evaluation study.

BACKGROUND: Reducing health inequalities is a top priority of the public health agendas in Europe. The EPHE project aims to analyse the added value of a community-based interventional programme based on EPODE methodology, adapted for the reduction of socio-economic inequalities in childhood obesity. The interventions that will be implemented by this project focus on four energy balance-related behaviours (fruit and vegetable consumption, tap water intake, physical inactivity, sleep duration) and their determinants. This article presents the design of the effect evaluation of the EPHE project. METHODS/DESIGN: This is a prospective two-year follow-up evaluation study, which will collect data on the energy balance-related behaviours and potential environmental determinants of 6-8 year olds, depending on the socio-economic status of the parents. For this purpose a parental self-reported questionnaire is constructed. This assesses the socio-economic status of the parents (5 items) and the dietary (12 items), sedentary (2 items) and sleeping (4 items) behaviour of the child. Alongside potential family-environmental determinants are assessed. The EPHE parental questionnaire will be disseminated in schools of a selected medium-sized city in seven European countries (Belgium, Bulgaria, France, Greece, Portugal, Romania, The Netherlands). DISCUSSION: This study will evaluate the effects of the EPHE community-based interventional programmes. Furthermore, it will provide evidence for children's specific energy balance-related behaviours and family environmental determinants related to socio-economic inequalities, in seven European countries.

Parent-offspring correlations in pedometer-assessed physical activity.

BACKGROUND: Physical activity is a major component of a healthy lifestyle in youth and adults. To identify determinants of this complex behavior is an important research objective in the process of designing interventions to promote physical activity at population level. In addition to individual determinants, there is evidence documenting familial influences on physical activity. However, the few studies that have addressed this issue with objective measures did not provide data on parent-offspring physical activity relationships throughout childhood and adolescence. The purpose of this study was to assess familial correlations in pedometer-assessed physical activity. METHODS: We measured ambulatory activity in 286 French nuclear families (283 mothers, 237 fathers, and 631 children aged 8-18 years) by pedometer recordings (Yamax Digiwalker DW 450) over a week. Correlations were computed with their 95% confidence intervals (CI) for spouse pairs, siblings, mother-offspring, and father-offspring. Data were expressed as steps per day and computed both for the full recording period and separately for weekdays and weekends. RESULTS: The correlations were the highest between siblings (r=0.28, 95%CI: 0.17-0.38). Parent-offspring correlations were significant in mothers (r=0.21, 95%CI: 0.12-0.30), especially between mothers and daughters (r=0.24, 95%CI: 0.12-0.36 vs. r=0.18, 95%CI: 0.05-0.31 for sons), but were almost nonexistent in fathers. Correlations were generally higher on weekend days compared to weekdays. Mother-offspring correlations did not decrease with increasing age of children (r=0.17, 95%CI: 0.00-0.34 in 8-11-year-olds, r=0.20, 95%CI: 0.07-0.33 in 12-15-year-olds, and r=0.25, 95%CI: 0.07-0.39 in ≥16-year-olds). Finally, between-spouse correlations were significant only during weekend days (r=0.14, 95%CI: 0.01-0.27). CONCLUSION: Ambulatory activity correlated within families, with a possible mother effect. Mother-offspring correlations remained significant through the transition from childhood to adolescence. Further studies are required to better understand the respective influences of shared activities, parental modeling and support as well as genetic factors on the familial aggregation of physical activity.

Parental body size and early weight and height growth velocities in their offspring.

BACKGROUND: Whereas weight or height at a given age are the results of the cumulative growth experience, growth velocities allows the study of factors affecting growth at given ages. AIM: To study the relationships between parental height and body mass index (BMI) and offspring's height and weight growth during infancy and childhood. STUDY DESIGN: From the FLVSII population-based study, 235 parent-child trios belonging to 162 families examined in 1999. OUTCOME MEASURES: From medical records and previous FLVS examinations, child's height and weight history were reconstructed. Weight and height growth velocities from birth to seven years were estimated from a modelling of individual growth curve and correlated with parent's body size in 1999. RESULTS: Ponderal index and length at birth were significantly associated with maternal but not paternal BMI and height. In the first six months, height growth velocity was significantly associated with maternal stature (at three months: 0.12+/-0.05 and 0.02+/-0.05 cm/month for a 10 cm difference in maternal and paternal height respectively) and weight growth velocity with paternal BMI (at three months: 5.7+/-2.8 and 1.9+/-2.3g/month for a difference of 1 kg/m(2) in paternal and maternal BMI respectively). Between two and five years, height growth velocity was more significantly associated with paternal height whereas weight growth velocity was more closely associated with maternal BMI. CONCLUSIONS: Early childhood growth is characterised by alternate periods associated specifically with maternal or paternal BMI and height. This novel finding should trigger the search for specific genetic, epigenetic or environmentally shared factors from the mothers and fathers.

Relationships of self-reported physical activity domains with accelerometry recordings in French adults.

The objective was to examine the relationships of self-reported physical activity (PA) by domain (leisure, occupational, other) with PA and sedentary time as measured objectively by accelerometry. Subjects were adults with low habitual PA levels from a community in northern France. Among subjects in the lowest tertile of a PA score from a screening questionnaire, 160 (37% males, age: 41.0 +/- 10.8 years, BMI: 25.1 +/- 4.1 kg/m(2), mean +/- SD) completed a detailed instrument (Modifiable Activity Questionnaire), and wore an accelerometer (Actigraph) for seven consecutive days. Relationships between questionnaire domains (occupational, leisure, and "non-occupational non-leisure") and accelerometry measures (total activity and sedentary time) were assessed using Spearman correlation coefficients. In this population, the highest contributor to total reported PA (h/week) was occupational PA. Time spent in non-occupational non-leisure PA ranked second in women and third in men. The most frequent non-occupational non-leisure PA were shopping and household chores. In women, non-occupational non-leisure PA contributed more than occupational or leisure-time PA to total PA energy expenditure (median: 18.0, 9.1, and 4.9 MET-h/week, respectively). Total PA by accelerometry (count/day) was correlated to leisure-time PA in women (r = 0.22, P < 0.05) and to occupational (r = 0.43, P < 0.01) and total reported PA (r = 0.39, P < 0.01) in men (all in MET-h/week). There was an inverse relationship between accelerometry sedentary time (h/day) and non-occupational non-leisure PA (MET-h/week, r = -0.30, P < 0.001). These findings indicate the importance of assessing non-occupational non-leisure PA for a better understanding of how individuals partition their time between active or sedentary occupations.

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.

Cardiovascular risk factor levels and their relationships with overweight and fat distribution in children: the Fleurbaix Laventie Ville Santé II study.

This study aimed to document for the first time in a general population of French children the prevalence and levels of cardiovascular risk factors and to assess separately in boys and girls whether these risk factors were associated with fat mass distribution independently of subcutaneous overall adiposity. A cross-sectional analysis of baseline data from 452 children (235 boys and 217 girls) aged 8 to 17 years included in a 1999 population-based epidemiologic study (the Fleurbaix Laventie Ville Santé II study) was made. Overweight was defined according to the International Obesity Task Force references and the 90th percentiles of the French body mass index curves. The thresholds of parameters defining cardiovascular and metabolic risks were the 95th percentile of the Task Force Report on High Blood Pressure in Children and Adolescents for blood pressure and those of the American Academy of Pediatrics for lipids. Anthropometric and biological parameters were described by sex and according to overweight status. Partial correlations between cardiovascular risk factors and anthropometric measures of adiposity (body mass index, sum of 4 skinfold thicknesses, waist circumference, waist-to-height ratio) were calculated. Then, these correlations were additionally adjusted for the sum of 4 skinfold thicknesses. High plasma triglycerides, high insulin concentration, and low plasma high-density lipoprotein cholesterol (HDL-C) concentration were associated with all measures of adiposity (|r| > or = 0.20, P < .002). When obese children were excluded, overweight children already had high triglycerides and low HDL-C levels, respectively, 2 and 20 times more frequently than normal-weight children did. Among overweight children, 7.7% had at least 2 risk factors among high blood pressure, high plasma triglycerides or glucose, and low HDL-C concentration vs 0.25% among normal-weight children (P = .002). After adjusting for the sum of skinfolds, an independent association between the risk factors and waist circumference was found in girls. In conclusion, (a) modest excess weight is associated with increased levels of cardiovascular risk factors. (b) In girls, abdominal fat distribution is associated with cardiovascular risk factors, independently of overall adiposity. (c) International definition of abdominal obesity in children is required to standardize studies and to progress in the evaluation of childhood obesity and its consequences.

Serum adiponectin is related to plasma high-density lipoprotein cholesterol but not to plasma insulin-concentration in healthy children: the FLVS II study.

Although low levels of plasma adiponectin were associated with an increase in cardiovascular risk in adults, few data investigated that relationship in children. The aim of this study was to investigate the relationship between plasma adiponectin and cardiovascular risk factors in healthy children. This cross-sectional population-based study was conducted in Fleurbaix and Laventie, 2 cities in the north of France. The main outcome measure was the correlations between plasma adiponectin and adiposity variables (the body mass index, the sum of 4 skinfolds, waist circumference [WC], and percent body fat [bioimpedance]), blood pressure, plasma glucose, triglycerides, high-density lipoprotein (HDL) cholesterol and insulin. In 398 children of both sexes, adiponectin was not significantly related to age and pubertal stage. In boys only, adiponectin correlated with WC (r = -0.19; P = .008) and body mass index (r = -0.15; P = .04) but not with other adiposity variables. After taking into account WC, adiponectin was positively correlated with HDL-cholesterol in boys (r = 0.14; P = .05) and girls (r = 0.25; P = .0004), but was not correlated with insulin and homeostasis model assessment index for insulin resistance in both sexes. These results suggest that, in apparently healthy children, adiponectin is related to the level of HDL-cholesterol independently of fat mass. The relationship between adiponectin and insulin resistance previously reported in obese or diabetic children was not apparent in these subjects and may therefore occur only at later age with fat accumulation.

Is restrained eating a risk factor for weight gain in a general population?

BACKGROUND: In modern societies characterized by abundant and accessible foods, restrained eating may become an adaptive behavior to limit weight gain. OBJECTIVE: We assessed the relations between eating behavior (EB) and adiposity in a general population over a 2-y period. DESIGN: We recruited 466 adults and 271 adolescents in 1999 on a geographical basis to participate in a longitudinal study. At the initial examination and 2 y later, they answered an EB questionnaire, the Three-Factor Eating Questionnaire-R18, which measured cognitive restraint (CR), uncontrolled eating, and emotional eating. On the same occasions, several measures of adiposity were also obtained: body mass index (BMI; in kg/m2), waist circumference, the sum of 4 skinfold thicknesses, and percentage body fat. Relations between EB and adiposity were tested separately in adults and adolescents by using mixed linear regressions after adjustment for age, sex, and (in adolescents) Tanner pubertal stage. RESULTS: At baseline, CR was positively associated with BMI in normal-weight subjects (mean BMI: 21.4 in the lowest to 23.3 in the highest CR quintile; P < 0.001) but not in overweight adults (P = 0.25). Initial CR did not predict change in adiposity variables (BMI change: P = 0.79 in adults, P = 0.57 in adolescents and young adults). Conversely, a high initial BMI was associated with a larger increase in CR (beta = 20.1, P < 0.0001 in adults; beta = 21.7, P = 0.003 in adolescents and young adults). CONCLUSIONS: Restrained eating is strongly associated with adiposity in normal-weight subjects but not in overweight subjects. However, restrained eating does not promote weight gain.