Genetic markers of obesity risk: stronger associations with body composition in overweight compared to normal-weight children

Background

Genetic factors are important determinants of overweight. We examined whether there are differential effect sizes depending on children''s body composition.

Methods

We analysed data of n = 4,837 children recorded in the Avon Longitudinal Study of Parents and Children (ALSPAC), applying quantile regression with sex- and age-specific standard deviation scores (SDS) of body mass index (BMI) or with body fat mass index and fat-free mass index at 9 years as outcome variables and an “obesity-risk-allele score” based on eight genetic variants known to be associated with childhood BMI as the explanatory variable.

Results

The quantile regression coefficients increased with increasing child''s BMI-SDS and fat mass index percentiles, indicating larger effects of the genetic factors at higher percentiles. While the associations with BMI-SDS were of similar size in medium and high BMI quantiles (40th percentile and above), effect sizes with fat mass index increased over the whole fat mass index distribution. For example, the fat mass index of a normal-weight (50th percentile) child was increased by 0.13 kg/m² (95% confidence interval (CI): 0.09, 0.16) per additional allele, compared to 0.24 kg/m² per allele (95% CI: 0.15, 0.32) in children at the 90th percentile. The genetic associations with fat-free mass index were weaker and the quantile regression effects less pronounced than those on fat mass index.

Conclusions

Genetic risk factors for childhood overweight appear to have greater effects on fatter children. Interaction of known genetic factors with environmental or unknown genetic factors might provide a potential explanation of these findings.     

Relationship between overweight, obesity and socioeconomic factors of adolescents in Vojvodina, Serbia

Obesity is a very important issue in developed societies and depends on many factors. The aim of this paper was to determine a possible relationship between overweight, obesity and socioeconomic factors among adolescents in Vojvodina. A cross-sectional anthropometric study was carried out from 2001 to 2004 in towns of Vojvodina, northern Serbia. The research included height and body weight measurements as well as body mass index (BMI) of 1236 schoolboys and 1414 schoolgirls aged 15–18 years. The socioeconomic factors (SES) included parents’ level of education and monthly income per family member. The overweight prevalence of about 10% (85 < P < 95) and the prevalence of obesity of 5% (P > 95) were recorded in both male and female adolescents. A significant correlation (p < 0.01) between all socioeconomic factors was observed in male subjects, although there were no significant differences in the prevalence of overweight and obesity when different categories of subjects set by SES were compared. In females lower rates of the prevalence of overweight and obesity were detected in the subjects whose parents had a university education, but the difference was not significant. Regarding the prevalence of obesity, a significant difference was recorded between females with high and low incomes, those with a high income showing significantly greater prevalence of obesity than females coming from low income families. The results of the research indicate that in Vojvodina the family income is the only factor that significantly correlates with female obesity.     

Dietary behaviors as associated factors for overweight and obesity in a sample of adolescents from Aquitaine, France

This study aimed to identify dietary behaviors that might be considered as associated factors for overweight or obesity among French adolescents. Forty-nine of the 536 middle and high schools in Aquitaine (southwest of France) were invited to take part in the study. For each school, participating adolescents were selected using stratification by grade. A self-report questionnaire, including information about sex, age, dietary behaviors, physical and sedentary activities, and parental socioeconomic status (SES), was filled in by adolescents during class. Overweight and obesity were defined according to the age- and sex-specific body mass index cutoff points of the International Obesity Task Force. Multivariate analysis (logistic regression) was used to identify independent dietary factors associated with overweight including obesity and obesity alone (adjustment on sex, age, parental SES, and weight status and adolescents' sedentary activity). In addition to parental SES and weight status and adolescents' sedentary activity, some dietary behaviors are also independently and significantly associated with a higher prevalence of overweight including obesity: absence (OR 1.43, 0.91–2.23) or rare (OR 1.57, 1.23–2.01) breakfast intake (p?<?0.01) and absence (OR 5.03, 3.19–7.92) or rare (OR 1.90, 1.46–2.47) light afternoon meal intake (p?<?0.001). All variables were also significantly and independently associated with obesity alone. This study shows that socioeconomic factors and individual behaviors are associated with overweight or obesity. These results confirm the importance to carry out multifaceted educational actions among adolescents, by promoting physical activity and healthy food choices in order to prevent overweight and promote healthy lifestyle behaviors.     

Epidemiological survey for the prevalence of overweight and abdominal obesity in Greek adolescents

This study was designed to provide estimates of overweight (OW), obesity (OB), and abdominal OB (AO) in a representative sample of adolescents throughout the whole of Greece. A total of 14,456 adolescents aged 13-19 years (6,677 boys and 7,779 girls) had direct measurements (height, weight, waist circumference (WC)) taken at school during 2003. The overall prevalence of OW including OB in the population studied was 29.4% in boys and 16.7% in girls. OB prevalence was also higher in boys than in girls (6.1% vs. 2.7%), whereas prevalence of AO was higher in girls than in boys (21.7% vs. 13.5%). Rates of OW, OB, and AO were significantly more prevalent in the Greek than in the foreign male population (immigrants). OW% in adolescent girls was independently associated with smoking and alcohol consumption. The prevalence of OW and OB in Greek adolescents is high, particularly in boys, comparable with that reported for most Mediterranean European countries. AO, mainly in adolescent girls, also appears high. Preventive and treatment strategies are urgently needed to combat this OB epidemic in Greece.     

SDCCAG8 obesity alleles and reduced weight loss after a lifestyle intervention in overweight children and adolescents

Genome-wide association analyses (GWAS) contributed to the detection of a number of single-nucleotide polymorphisms (SNPs) associated with obesity. However, little is known about the impact of the obesity-risk alleles on weight loss-related phenotypes after lifestyle interventions. A recent meta-analysis of GWAS reported five genomic loci near or in the genes FTO, MC4R, TMEM18, SDCCAG8, TNKS/MSRA that were associated with obesity in children and adolescents. Here, we analyzed the effect of the 10 SNPs representative of the five loci on measures of weight loss and cardiometabolic risk after a 1-year lifestyle intervention in 401 children and adolescents (mean age 10.74 years; 55.4% female; mean BMI 27.42 kg/m(2), mean BMI-standard deviation score (SDS) 2.37). For confirmation of one locus genotyping of three intronic SNPs in SDCCAG8 was performed in 626 obese adults who completed the 10-week hypoenergetic diet program. Intronic variants of SDCCAG8, which are associated with early onset obesity, are associated with reduced weight loss after a 1-year lifestyle intervention in overweight children and adolescents even after adjusting for age, sex, baseline measurement, or multiple testing (all P < 10(-6)). However, our results could not be confirmed in 626 obese adults undertaking a hypoenergetic diet intervention.     

The relationships between serum copper levels and overweight/total obesity and central obesity in children and adolescents aged 6-18 years

ObjectiveTo explore the relationships between serum copper levels and overweight/total obesity and central obesity in children and adolescents.MethodsWe included 2,000 children and adolescents from the 2011-2016 US National Health and Nutrition Examination Surveys. The multivariable linear model, logistic model and restricted cubic splines were adopted to assess the relationships. Models were adjusted for data release cycle, age, sex, race/ethnicity, ratio of family income to poverty, and dietary intakes of protein, total sugars, total fat, fiber, energy, calcium, vitamin D, vitamin C, and hours watch television or videos.ResultsThe prevalences of overweight/total obesity and central obesity were 37.38% and 33.40%, respectively. For per-quintile increment in serum copper levels, body mass index increased by 1.06 (0.79-1.33) (kg/m²) and waist circumference increased by 2.43 (1.58-3.27) (cm). The odds ratios (95% confidence intervals) for overweight/total obesity and central obesity among participants with the highest quintile compared with those with the lowest quintile of serum copper levels were 5.46 (3.31-8.98) and 5.64 (3.31-9.58), respectively. The above-mentioned associations were not modified by age (children: 6-12 years, adolescents: 13-18 years) and sex. Dose-response analysis showed that the odds of overweight/total obesity and central obesity increased with increasing serum copper levels to a level of approximate 140 ug/dL where the association seemed to reach a plateau, respectively.ConclusionsSerum copper levels were positively associated with body mass index and waist circumference, and elevated serum copper levels were associated with higher odds of overweight/total obesity and central obesity in children and adolescents.     

Body mass index, prevalence of overweight and obesity in Lithuanian children and adolescents, 1985-2002

The study provides the body mass index (BMI), the prevalence of overweight (OW) and obesity (OB) in Lithuanian children and adolescents, 1985-2002. In the 2000-2002 more than 9000 schoolchildren of 7-18 years old were investigated in the 5 biggest towns and surrounding settlements of Lithuania. These data were compared with the 1985 data. The prevalence of OW and OB was estimated using the International Obesity Task Force (IOTF) cut-off points. The prevalence of OW in Lithuanian children and adolescents was higher among younger schoolchildren in comparison with older adolescents. OW was lower among the older girls in comparison with the older boys: 4.60%-11.50%/4.80%0-13.62% in the 7-13 years girls/boys, versus 1.50%-6.60%/3.90%-9.50% in the 14-18 years old girls/boys. The prevalence of OW among younger Lithuanian adolescents did not change significantly in the last 15 years, but it slightly decreased in older boys and demonstrably diminished in older adolescent girls. In generally, the prevalence of OW among Lithuanian adolescents is low in comparison with the prevalence of OW in children from the other countries.     

Prevalence of overweight and obesity in 2- to 6-year-old Italian children

Objective: To assess the prevalence of overweight and obesity in 2‐ to 6‐year‐old Italian children and to compare the prevalence between the north and the south of the country. Research Methods and Procedures: This was a cross‐sectional study of 2150 subjects (M/F: 1137/1013), 5.36 ± 0.83 years of age. The sampling areas were Verona (north Italy) and Messina (south Italy). We used definitions of overweight and obesity using BMI values, with cut‐off values proposed by the International Obesity Task Force. Results: The prevalence of overweight was 16.6% (males: 13.9%, females: 19.6%), and it was higher in the south (males: 17.8%, females: 22.4%) than in the north (males: 11.3%, females: 17.9%). The prevalence of obesity was 8.0% (males: 8.3%, females: 7.7%), and it was higher in the south (males: 12.3%, females: 10.7%) than in the north (males: 5.7%, females: 5.8%). Using the Centers for Disease Control reference charts, the prevalence of overweight and obesity of Italian children was close to that reported in children living in the United States (32% vs. 32.7%, respectively). Discussion: The prevalence of overweight and obesity in young Italian children is very high, and it is rapidly growing. In the south of the country, the prevalence is higher than in the north.     

Headaches in overweight children and adolescents referred to a tertiary-care center in Israel

Objective: To assess the association between obesity and primary headaches in children and adolescents. Methods and Procedures: In a prospective study, the short‐questionnaire version based on existing International Headache Society diagnostic criteria was administered. Two hundred and seventy‐three children and adolescents (61% females) aged 9–17 years were assessed. One hundred and sixteen (42.5%) subjects were of normal weight, 45 (16.5%) were at risk for overweight (BMI >85th and <95th percentile for age and gender) and 112 (41%) were overweight (BMI ≥95th percentile). The outcome measures were prevalence of headaches, type of headaches, association between headaches and elevated blood pressure in overweight subjects. Results: Headache was reported in 39 (14.3%) subjects, with a similar rate in females (14.5%) and males (14%). Among 39 subjects with headaches, 20 (17.9%) were overweight, 7 (15.6%) were at risk for overweight and 12 (10.3%) were normal‐weight children. Among females, 7.7% of normal‐weight group suffered from headaches, compared with 14.8% of the at risk for overweight group and 20.3% of the overweight group (P for trend 0.04). Among males, the occurrence of headaches was similar in all three weight groups (P = 0.96). The occurrence of headaches increased from 10.6% among children aged 9–11 years to 21.8% in the 15–18 years age group (P < 0.05). In multivariate analysis, a significant independent risk for headaches was present in overweight females (odds ratio (OR) = 3.93, 95% confidence interval (CI) 1.28–12.1) and in adolescents aged 15–18 years (OR = 2.62, 95% CI 1.07–6.45). Elevated blood pressure was not independently associated with headaches. Of the 15 children with migraine, 12 were either at risk for overweight or overweight. Discussion: Overweight females had an almost fourfold excess risk of headaches when compared with normal‐weight girls.     

Long term pharmacotherapy for obesity and overweight: updated meta-analysis

Objective To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.Design Updated meta-analysis of randomised trials.Data sources Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles. All data sources were searched from December 2002 (end date of last search) to December 2006.Studies reviewed Double blind randomised placebo controlled trials of approved anti-obesity dugs used in adults (age over 18) for one year or longer.Results 30 trials of one to four years’ duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365). Of these, 14 trials were new and 16 had previously been identified. Attrition rates averaged 30-40%. Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg). Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds. Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein. Sibutramine lowered concentrations of high density lipoprotein cholesterol and triglycerides but raised blood pressure and pulse rate. Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.Conclusions Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.     

The lifetime medical cost burden of overweight and obesity: implications for obesity prevention

This study quantifies age-specific and lifetime costs for overweight (BMI: 25-29.9), obese I (BMI: 30-34.9), and obese II/III (BMI: >35) adults separately by race/gender strata. We use these results to demonstrate why private sector firms are likely to underinvest in obesity prevention efforts. Not only does the existence of Medicare reduce the economic burden that obesity imposes on private payers, but, from the perspective of a 20-year-old obese adult, the short-term costs of obesity are small. This suggests that legislation that subsidizes wellness programs and/or mandates coverage for obesity treatments might make all firms better off. Ironically, Medicare has a greater incentive to prevent obesity because when an obese 65 year old enters the program, his/her costs are immediate and higher than costs for normal weight individuals.     

Plasma androgens in children and adolescents. Part I: control subjects

In this cross-sectional study, plasma levels of dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), delta 4-androstenedione (delta 4) and testosterone (T) were measured by RIA in 232 normal subjects of both sexes, aged 2 weeks to 20 years. The results were analyzed in relation to chronological age, body surface and pubertal stage. High levels of plasma androgens were found in newborn infants of both sexes. After 3 months of age, androgen levels were uniformly low and rose with increasing chronological age and body surface. The first significant increase in mean androgen levels was found for DHEA-S. It occurred after 6 years of age in girls and after 8 years in boys. DHEA and T rose in both sexes after 8 years of age. delta 4 increased steadily with chronological age and body surface in both sexes. When androgen levels were related to body surface, a first significant increase was observed above 1.00 m2 for the four androgens, in both boys and girls. Above 1.20 m2 and 12 years of age, girls had higher mean levels of DHEA-S, DHEA and delta 4, but lower mean T levels than boys of the same body surface and chronological age. Before puberty, a positive correlation was found in both sexes between the plasma androgen levels on the one hand, and both chronological age and body surface on the other. Plasma androgen levels markedly increased at stage P2 in both sexes, and further increased with pubertal development. During puberty, girls had higher plasma delta 4, but lower plasma T levels than boys of the same pubertal stage. Plasma DHEA-S and DHEA levels were similar in both sexes. In contrast to the plasma androgens, plasma cortisol levels did not show any change in relation either to chronological age or to body surface or pubertal development. Body surface appears to be as good a discriminating factor as chronological age, at least in young children. It also appears from this study that DHEA-S is a good guide for the clinical evaluation of adrenal maturation and may be very useful in evaluating patients with growth or pubertal disturbances.     

Changes in BMI and the prevalence of overweight and obesity in children and adolescents in Cracow, Poland, 1971-2000.

The aim of this study is to examine changes in prevalence of overweight and obesity, using International Obesity Task Force criteria, in three cohorts of children and youth living in Cracow, Poland, in 1971, 1983 and 2000. Rates of overweight and obesity doubled among boys and girls, from 7.5% and 6.5% in 1971, to 15.2% and 11.8% in the year 2000. The greatest increases in prevalence occurred in the youngest age groups (7-12 years for boys and 7-10 years for girls), increases being less extensive among adolescents, and lowest of all in the oldest age groups (16-18 years in boys and 14-18 years in girls). The absence of a positive secular trend in BMI among adolescent females relative to males may be due to sociocultural pressures associated with transition to a free market economy in Poland. The extent to which girls attempt to achieve the ideal body, as portrayed by media and society more generally, increases across adolescence.     

Assessment of obesity stigmatization in children and adolescents: modernizing a standard measure

Objective: Stigmatization of overweight children is highly prevalent. However, the measurement of stigma has varied widely across studies. An up‐to‐date version of a commonly used measure of weight‐related stigma is needed. Research Methods and Procedures: Poser 5 (DAZ software) was used to develop 12 modernized figures, using three‐dimensional models rendered as high‐resolution images. They depicted one overweight, one non‐overweight, and four disabled children of each sex. Children recruited from public and private schools (N = 261; mean age, 11.3 years; median BMI z‐score = 0.33; 77.0% white, 11.5% Asian, and 7.7% Maori) ranked these figures in order of liking. Participants also ranked traditionally used line drawings depicting comparable images. Participants rated each new figure on measures of liking and stereotypical attributes on 100‐mm visual analog scales (VASs). Results: Rankings of liking of the new figures were highly correlated with rankings of corresponding old figures, especially for overweight figures [boys: ρ (77) = 0.72, p < 0.001; girls: ρ (153) = 0.68, p < 0.001]. Rankings of overweight and other figures were also highly correlated with VAS assessment of liking and with a composite, internally consistent VAS measure of liking and stereotypical attributes. Only negative stereotypes about the intelligence of overweight boys and girls contributed significantly to the variance in liking. Discussion: An updated and modernized tool for assessing children's weight stigma was developed and its construct validity supported. The present findings suggest that stereotypes about low intelligence may contribute to weight stigma among children. More research is needed on the causes and components of weight stigma so that it can be effectively reduced.     

Utility of the modified ATP III defined metabolic syndrome and severe obesity as predictors of insulin resistance in overweight children and adolescents: a cross-sectional study

Background

Inhibition of vascular smooth muscle cell (vSMC) proliferation by oral anti-hyperglycemic agents may have a role to play in the amelioration of vascular disease in diabetes. Thiazolidinediones (TZDs) inhibit vSMC proliferation but it has been reported that they anomalously stimulate [³H]-thymidine incorporation. We investigated three TZDs, two biguanides and two sulfonylureas for their ability of inhibit vSMC proliferation. People with diabetes obviously have fluctuating blood glucose levels thus we determined the effect of media glucose concentration on the inhibitory activity of TZDs in a vSMC preparation that grew considerably more rapidly under high glucose conditions. We further explored the mechanisms by which TZDs increase [³H]-thymidine incorporation.

Methods

VSMC proliferation was investigated by [³H]-thymidine incorporation into DNA and cell counting. Activation and inhibition of thymidine kinase utilized short term [³H]-thymidine uptake. Cell cycle events were analyzed by FACS.

Results

VSMC cells grown for 3 days in DMEM with 5% fetal calf serum under low (5 mM glucose) and high (25 mM glucose) increased in number by 2.5 and 4.7 fold, respectively. Rosiglitazone and pioglitazone showed modest but statistically significantly greater inhibitory activity under high versus low glucose conditions (P < 0.05 and P < 0.001, respectively). We confirmed an earlier report that troglitazone (at low concentrations) causes enhanced incorporation of [³H]-thymidine into DNA but did not increase cell numbers. Troglitazone inhibited serum mediated thymidine kinase induction in a concentration dependent manner. FACS analysis showed that troglitazone and rosiglitazone but not pioglitazone placed a slightly higher percentage of cells in the S phase of a growing culture. Of the biguanides, metformin had no effect on proliferation assessed as [³H]-thymidine incorporation or cell numbers whereas phenformin was inhibitory in both assays albeit at high concentrations. The sulfonylureas chlorpropamide and gliclazide had no inhibitory effect on vSMC proliferation assessed by either [³H]-thymidine incorporation or cell numbers.

Conclusion

TZDs but not sulfonylureas nor biguanides (except phenformin at high concentrations) show favorable vascular actions assessed as inhibition of vSMC proliferation. The activity of rosiglitazone and pioglitazone is enhanced under high glucose conditions. These data provide further in vitro evidence for the potential efficacy of TZDs in preventing multiple cardiovascular diseases. However, the plethora of potentially beneficial actions of TZDs in cell and animal models have not been reflected in the results of major clinical trials and a greater understanding of these complex drugs is required to delineate their ultimate clinical utility in preventing macrovascular disease in diabetes.