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.     

Comparison of body composition methods in overweight and obese children.

The objective of the present study was to investigate the accuracy of percent body fat (%fat) estimates from dual-energy X-ray absorptiometry, air-displacement plethysmography (ADP), and total body water (TBW) against a criterion four-compartment (4C) model in overweight and obese children. A volunteer sample of 30 children (18 male and 12 female), age of (mean +/- SD) 14.10 +/- 1.83 yr, body mass index of 31.6 +/- 5.5 kg/m, and %fat (4C model) of 41.2 +/- 8.2%, was assessed. Body density measurements were converted to %fat estimates by using the general equation of Siri (ADPSiri) (Siri WE. Techniques for Measuring Body Composition. 1961) and the age- and gender-specific constants of Lohman (ADPLoh) (Lohman TG. Exercise and Sport Sciences Reviews. 1986). TBW measurements were converted to %fat estimates by assuming that water accounts for 73% of fat-free mass (TBW73) and by utilizing the age- and gender-specific water contents of Lohman (TBWLoh). All estimates of %fat were highly correlated with those of the 4C model (r > or = 0.95, P < 0.001; SE < or = 2.14). For %fat, the total error and mean difference +/- 95% limits of agreement compared with the 4C model were 2.50, 1.8 +/- 3.5 (ADPSiri); 1.82, -0.04 +/- 3.6 (ADPLoh); 2.86, -2.0 +/- 4.1 (TBW73); 1.90, -0.3 +/- 3.8 (TBWLoh); and 2.74, 1.9 +/- 4.0 DXA (dual-energy X-ray absorptiometry), respectively. In conclusion, in overweight and obese children, ADPLoh and TBWLoh were the most accurate methods of measuring %fat compared with a 4C model. However, all methods under consideration produced similar limits of agreement.     

Incidence of low birth weight infants born to mothers with multiple risk factors

Low birth weight (LBW) is associated with a large number and variety of risk conditions during pregnancy. The number and types of risk conditions per pregnancy were determined in 1,864 white and 872 black mothers delivered at the University of Kansas Medical Center between 1975 and 1978. The incidence of LBW infants increased steadily among white and black mothers as the number of risk factors increased from none to three or four per pregnancy. Among pregnancies without spontaneous premature rupture of membranes (PROM), 51 percent of the LBW infants were born to mothers who had multiple risk factors associated with their pregnancies, even though only 18 percent of these pregnancies were associated with multiple risk factors. Among pregnancies with PROM, 72 percent were associated with multiple risk conditions, and 31 percent resulted in LBW infants. About 90 percent of LBW infants from PROM pregnancies had mothers with multiple risk factors. For all numbers of risk conditions, black mothers had a higher incidence of LBW infants than white mothers. Among black mothers without spontaneous premature rupture of membranes (PROM), the incidence of LBW infants increased from 3.2 percent (10/308) in low (zero)-risk condition pregnancies to 33 percent (16/49) among mothers with three or four risk conditions during the pregnancy. Among white mothers without PROM, the incidence of LBW infants increased from 1.7 percent (12/708) in low (zero)-risk condition pregnancies to 30 percent (19/64) in pregnancies with three or four risk conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reference values for height, weight and body mass index of German born Turkish children

Turkish children and adolescents born in Northern Europe grow different from native Northern European children, but reference values for height, weight and BMI for these children do not exist. With this study, we intend to provide growth standards for German born Turkish children. Data were obtained from 797 Turkish children and adolescents born in Germany age 0-25.8 years (males), respectively 0-18.3 years (females). We generated synthetic reference values for height, weight, and BMI. The results show that Turkish children and adolescents are heavier after the age of 6 years, and that they remain short after puberty. Eighteen year old Turkish men, and 15-year-old Turkish women are shorter (males 175.2 cm vs. 180.4 cm, p < 0.05; females 159.3 cm vs. 165.0 cm, p < 0.05), and heavier than Germans. Six out of 53 young Turkish men and 9 out of 100 young Turkish women were obese. Twelve out of 53 young Turkish men (23%) and 18 out of 100 young Turkish women (18%) have fallen below the 3rd centile for height. It can be concluded that growth of Turkish children and adolescents born in Germany significantly differs from native children. Reference LMS values for body height, weight and BMI of German born Turkish boys and girls are presented.     

Birth weight and body composition in overweight Latino youth: a longitudinal analysis

To examine the associations between birth weight and BMI, and total body composition, in overweight Latino adolescents. Two hundred and forty-two overweight Latino children (baseline age = 11.1 +/- 1.7 years; BMI >or= 85th percentile) were measured annually for up to 6 years (2.6 +/- 1.4 observations/child, total 848 visits). Birth weight and history of gestational diabetes were obtained by parental interview. Visceral fat and subcutaneous abdominal fat were assessed by magnetic resonance imaging, while total body fat, total lean tissue mass (LTM), trunk fat, and lean tissue trunk mass were measured by dual-energy X-ray absorptiometry. BMI and BMI percentile were calculated using the Centers for Disease Control and Prevention age appropriate cutoffs. Longitudinal linear mixed effects (LME) modeling was used to evaluate the influence of birth weight on subsequent changes in body composition and distribution of fat across puberty. Birth weight significantly predicted BMI (P < 0.001), total trunk fat (P < 0.001), total trunk LTM (P < 0.001), total fat mass (FM) (P < 0.001), and total LTM (P < 0.001), but not subcutaneous (P = 0.534) or visceral fat (P = 0.593) at age 11 years. Longitudinally, as participants transitioned into puberty, birth weight did not significantly predict any of the body composition or fat distribution measures (P > 0.05). Birth weight is significantly associated with increased adiposity and LTM and negatively associated with trunk fat mass and trunk lean mass at baseline; however these relationships did not predict rate of change of any of the variables as the children progress through adolescence.     

Meal-related changes in ghrelin, peptide YY, and appetite in normal weight and overweight children

Objective: Ghrelin and peptide YY (PYY) are two gut hormones that have effects on appetite. Our objectives were to characterize the patterns of secretion of these hormones in response to feeding in school‐age children and determine whether there were differences between normal weight (NW) and overweight (OW) subjects. Methods and Procedures: This was a cross‐sectional study at one tertiary care center. Subjects were 7‐ to 11‐year‐old healthy NW and OW volunteers recruited from local advertisements. Following an overnight fast, the subjects were given a standardized breakfast and lunch and had nine hourly blood samples for total ghrelin and total PYY. We assessed whether ghrelin and PYY levels changed from the preprandial to postprandial state and corresponded to reported hunger/satiety. Results: Hunger ratings were similar between the two groups throughout the study period. Ghrelin was not suppressed after eating, did not rise prior to the next meal, and did not correspond to hunger ratings in either group. PYY increased postprandially and decreased preprandially in the NW group, but OW children exhibited this pattern for only part of the day. PYY levels incompletely corresponded to reported satiety in the OW group. Discussion: Mixed meal consumption had little effect on ghrelin secretion and a variable effect on PYY secretion in young children in our study. Differences that were observed between the groups do not suggest that an abnormality in their secretion contributes to the development of obesity.     

Follow-up of children born of bromocriptine-treated mothers

A survey carried out in France at the beginning of 1984 concerning development of children born of mothers treated with bromocriptine (BC) during part or all of the pregnancy showed the absence of any adverse effects of BC in 64 children born from 53 mothers. In 60 cases, BC was prescribed (2.5-7.5 mg/day) for hyperprolactinemia; 23 mothers were treated with BC for 4 weeks or less, and 23 others for 30 weeks or more. After a follow-up of between 6 months and 9 years, all children are normal. Psychological development in the 23 children born to mothers treated with BC during more than 30 weeks of pregnancy actually appears more precocious, with excellent scholastic performance in the oldest.     

Hyperuricemia and metabolic syndrome in children with overweight and obesity

ObjectiveTo study the prevalence of hyperuricemia in children with overweight or obesity and analyze the relation with metabolic syndrome and the diseases that define it.Materials and methodsThis is a cross-sectional prevalence study in 148 children recruited from pediatric endocrinology consultation, with overweight or obesity (12 ± 3 years, 48% boys, BMI 31.8 ± 6.1). We measured BMI, waist-height, waist circumference, blood pressure with standard instrumentation and glucose (fasting and after overload with 75 g), insulin resistance, cholesterol HDL, triglycerides and uric acid.ResultsThe prevalence of hyperuricemia was 53%. Patients with hyperuricemia had greater BMI (33.9 vs 30.6, p = 0.003), plus waist circumference (101.4 vs 91.1 cm, p < 0.001), higher blood pressure: systolic (123.4 vs 111.9 mm Hg, p < 0.001), diastolic (78.2 vs 68.7 mm Hg, p < 0.001). They presented greater blood glucose after overload oral glucose (107.5 vs 100.7 mg/dl, p = 0.03), insulin was higher (29.2 vs 20.7 mg/dl, p = 0.001) as well as HOMA IR (6.5 vs 4.4, p < 0.001) and HDL levels were lower (49.5 vs 54.4 mg/dl, p = 0.02).Uric acid's level which most is the likely diagnosis of metabolic syndrome corresponds to 5.4 mg/dl in our sample (sensitivity: 64% and specificity 62%).ConclusionThe prevalence of hyperuricemia in children with overweight and obesity is high. In the group of patients with obesity and hyperuricemia, we found out that the parameters measured to diagnose with metabolic syndrome were less favorable. Uric acid's level from where there is a higher possibility to see metabolic syndrome is 5.4 mg/dl.     

Trends in body mass index, prevalence of overweight and obesity in preschool Lithuanian children, 1986-2006

The study provides the body mass index (BMI), the prevalence of overweight and obesity in preschool Lithuanian children, 1986-2006. In the 2003-2006 more than 1000 preschool 3-6 year old children from Vilnius (the capital of Lithuania) were investigated according to the standard anthropometric methods. The prevalence of overweight (OW) and obesity (OB) was estimated according to the cut-off points recommended by the International Obesity Task Force (IOTF). Recent data were compared with the data of preschool children from the 1986 Vilnius study and with the data from the other countries. The BMI of preschool children did not change significantly during the last 20 years, except for the statistically significant BMI increment in 6 years old girls. The prevalence of OB among preschool Lithuanian children was low (0.8%-3.7% in boys, and 0-1.9% in girls) and did not change significantly during 1986-2006. The prevalence of OW was higher in preschool girls (10.7%-18.2%) in comparison with preschool boys (6.5%-12.4%). The significant increment of the prevalence of OW was observed among the 6-year-old girls from the 2006 study in comparison with the 1986 study. The possible socio-economic reasons of the defined trend in the BMI and prevalence of OW and OB among preschool Lithuanian children are discussed in the paper.     

Longitudinal changes in energy expenditure and body composition in obese women with normal and impaired glucose tolerance

Our primary objective was to evaluate changes in energy expenditure and body composition in women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM). A secondary objective was to examine the relationship between maternal leptin and nutrient metabolism. Fifteen obese women, eight with NGT and seven with GDM, were evaluated before conception (P), at 12-14 wk (E), and at 34-36 wk (L). Energy expenditure and glucose and fat metabolism were measured using indirect calorimetry. Basal hepatic glucose production was measured using [6,6-2H2]glucose and insulin sensitivity by euglycemic clamp. There was a significant increase (6.6 kg, P = 0.0001) in fat mass from P to L. There was a 30% (P = 0.0001) increase in basal O2 consumption (VO2, ml/min). There were no significant changes in carbohydrate oxidation during fasting or storage from P to L. There was, however, a significant (P = 0.0001) 150% increase in basal fat oxidation (mg/min) from P to L. Under hyperinsulinemic conditions, there were similar 25% increases in VO2 (P = 0.0001) from P to L in both groups. Because of the significant increases in insulin resistance from P to L, there was a significant (P = 0.0001) decrease in carbohydrate oxidation and storage. There was a net change from lipogenesis to lipolysis, i.e., fat oxidation (30-40 mg/min, P = 0.0001) from P to L. Serum leptin concentrations had a significant positive correlation with fat oxidation at E (r = 0.76, P = 0.005) and L (r = 0.72, P = 0.009). Pregnancy in obese women is associated with significant increases in fat mass and basal metabolic rate and an increased reliance on lipids both in the basal state and during the clamp. These modifications are similar in women with NGT and GDM. The increased reliance on fat metabolism is accompanied by a concomitant decrease in carbohydrate metabolism during hyperinsulinemia. The increase in fat oxidation may be related to increased maternal serum leptin.     

Longitudinal study of body weight changes in children: who is gaining and who is losing weight

Cross-sectional studies have reported significant temporal increases in prevalence of childhood obesity in both genders and various racial groups, but recently the rise has subsided. Childhood obesity prevention trials suggest that, on average, overweight/obese children lose body weight and nonoverweight children gain weight. This investigation tested the hypothesis that overweight children lose body weight/fat and nonoverweight children gain body weight/fat using a longitudinal research design that did not include an obesity prevention program. The participants were 451 children in 4th to 6th grades at baseline. Height, weight, and body fat were measured at month 0 and month 28. Each child's BMI percentile score was calculated specific for their age, gender and height. Higher BMI percentile scores and percent body fat at baseline were associated with larger decreases in BMI and percent body fat after 28 months. The BMI percentile mean for African-American girls increased whereas BMI percentile means for white boys and girls and African-American boys were stable over the 28-month study period. Estimates of obesity and overweight prevalence were stable because incidence and remission were similar. These findings support the hypothesis that overweight children tend to lose body weight and nonoverweight children tend to gain body weight.     

Developmental evaluation of children born to mothers occupationally exposed to waste anesthetic gases

BACKGROUND: The etiology of developmental delay in children is frequently unknown. Increasing evidence supports the possibility that environmental and occupational factors might be part of the basis for such delays. This study focuses on the development of children born to mothers who were exposed during their pregnancy to waste anesthetic gases. METHODS: The study population included 40 children aged 5-13 years born to female anesthesiologists and nurses working in operating rooms (OpRs) exposed to waste anesthetic gases, and 40 unexposed children born to female nurses and physicians who worked in hospitals during their pregnancy but did not work in OpRs. The unexposed group was matched for children's age and gender and maternal occupation (nurses vs. doctors). By means of standardized developmental tests, the present study population was evaluated for their medical and neurodevelopmental state. Questionnaires were given for the detection of attention and activity levels as perceived by the parents. Additional questionnaires dealt with information concerning developmental milestones, maternal and fetal morbidity, and gynecological history. RESULTS: No differences were noted between the groups as newborns or in developmental milestones at the age of 5-13 years; however, the mean score of gross motor ability was significantly lower in the exposed versus the unexposed group. Additionally, the mean score of the DSM-III-R Parent-Teacher Questionnaire (PTQ) (i.e., measure of inattention/hyperactivity) was higher in the exposed group. The level of exposure, as measured by the number of weekly hours in the OpRs, was significantly and negatively correlated with fine motor ability and the score of IQ performance. CONCLUSIONS: Our study supports the hypothesis that occupational exposure to anesthetic gases might be a risk factor for minor neurological deficits of children born to mothers who work in OpRs and therefore indicates the need for more studies in this area and perhaps more caution among OpR pregnant women and employers.     

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 influence of body composition, fat distribution, and sustained weight loss on left ventricular mass and geometry in obesity

Alterations in left ventricular mass and geometry vary along with the degree of obesity, but mechanisms underlying such covariation are not clear. In a case–control study, we examined how body composition and fat distribution relate to left ventricular structure and examine how sustained weight loss affects left ventricular mass and geometry. At the 10‐year follow‐up of the Swedish obese subjects (SOS) study cohort, we identified 44 patients with sustained weight losses after bariatric surgery (surgery group) and 44 matched obese control patients who remained weight stable (obese group). We also recruited 44 matched normal weight subjects (lean group). Dual‐energy X‐ray absorptiometry, computed tomography, and echocardiography were performed to evaluate body composition, fat distribution, and left ventricular structure. BMI was 42.5 kg/m², 31.5 kg/m², and 24.4 kg/m² for the obese, surgery, and lean groups, respectively. Corresponding values for left ventricular mass were 201.4 g, 157.7 g, and 133.9 g (P < 0.001). In multivariate analyses, left ventricular diastolic dimension was predicted by lean body mass (β = 0.03, P < 0.001); left ventricular wall thickness by visceral adipose tissue (β = 0.11, P < 0.001) and systolic blood pressure (β = 0.02, P = 0.019); left ventricular mass by lean body mass (β = 1.23, P < 0.001), total body fat (β = 1.15, P < 0.001) and systolic blood pressure (β = 2.72, P = 0.047); and relative wall thickness by visceral adipose tissue (β = 0.02, P < 0.001). Left ventricular adjustment to body size is dependent on body composition and fat distribution, regardless of blood pressure levels. Obesity is associated with concentric left ventricular remodeling and sustained 10‐year weight loss results in lower cavity size, wall thickness and mass.