Left ventricular growth from age 8 to 18 and its anthropometric determinants: Longitudinal results from Project Heartbeat!

Left ventricular mass (LVM) is a strong predictor of cardiovascular disease (CVD) in adults. However, normal growth of LVM in healthy children is not well understood, and previous results on independent effects of body size and body fatness on LVM have been inconsistent. The purpose of this study was (1) to establish the normal growth curve of LVM from age 8 to age 18, and evaluate the determinants of change in LVM with age, and (2) to assess the independent effects of body size and body fatness on LVM.^ In Project HeartBeat!, 678 healthy children aged 8, 11 and 14 years at baseline were enrolled and examined at 4-monthly intervals for up to 4 years. A synthetic cohort with continuous observations from age 8 to 18 years was constructed. A total of 4608 LVM measurements was made from M-mode echocardiography. The multilevel linear model was used for analysis.^ Sex-specific trajectories of normal growth of LVM from age 8 to 18 was displayed. On average, LVM was 15 g higher in males than females. Average LVM increased linearly in males from 78 g at age 8 to 145 g at age 18. For females, the trajectory was curvilinear, nearly constant after age 14. No significant racial differences were found. After adjustment for the effects of body size and body fatness, average LVM decreased slightly from age 8 to 18, and sex differences in changes of LVM remained constant.^ The impact of body size on LVM was examined by adding to a basic LVM-sex-age model one of 9 body size indicators. The impact of body fatness was tested by further introducing into each of the 9 LVM models (with one or another of the body size indicators) one of 4 body fatness indicators, yielding 36 models with different body size and body fatness combinations. The results indicated that effects of body size on LVM can be distinguished between fat-free body mass and fat body mass, both being independent, positive predictors. The former is the stronger determinant. When a non-fat-free body size indicator is used as predictor, the estimated residual effect of body fatness on LVM becomes negative. ^

FEMALE SEXUAL MATURATION AND BLOOD PRESSURE (SECONDARY-SEX CHARACTERISTICS, GROWTH, DEVELOPMENT)

This study described the relationship of sexual maturation and blood pressure in a sample (n = 361) of white females, ages seven through 18, attending public schools in a defined area of Central Texas during October through December, 1984. Other correlates of blood pressure were also described for this sample.^ A survey was performed to obtain the data on height, weight, body mass, pulse rate, upper arm circumference and length, and blood pressure. Each subject self-assessed her secondary sex characteristics (breast and pubic hair) according to drawings of the Tanner stages of maturation. The subjects were interviewed to obtain data on personal health habits and menstrual status. Student age, ethnic group and place of residence were abstracted from school records. Parents or guardians of the subjects responded to a questionnaire pertaining to parental and subject health history and parents' occupation and educational attainment.^ In the simple linear regression analysis, sexual maturation and variables of body size were significantly (p < 0.001) and positively associated with systolic and fourth- and fifth-phase diastolic blood pressure. The demographic and socioeconomic variables were not sufficiently variant in this population to have differential effects on the relation between blood pressure and maturation. Stepwise multiple regression was used to assess the contribution of sexual maturation to the variance of blood pressure after accounting for the variables of body size. Sexual maturation (breast stage) along with weight, height and body mass remained in the multiple regression models for fourth- and fifth-phase diastolic blood pressure. Only height and body mass remained in the regression model for systolic blood pressure; sexual maturation did not contribute more to the explanation of the systolic blood pressure variance.^ The association of sexual maturation with blood pressure level was established in this sample of young white females. More research is needed first, to determine if this relationship prevails in other populations of young females, and second, to determine the relationship of sexual maturation sequence and change with the change of blood pressure during childhood and adolescence. ^

Linkage and association of candidate obesity genes in Mexican-Americans from Starr County, Texas

Obesity and related chronic diseases represent a tremendous public health burden among Mexican Americans, a young and rapidly-expanding population. This study investigated the impact of variation within eight candidate obesity genes, which include leptin (LEP), leptin receptor (LEPR), neuropeptide Y (NPY), NPYY1 receptor (NPYY1), glucagon-like peptide-1 (GLP-1), GLP-1 receptor (GLP1R), beta-3 adrenergic receptor (β3AR), and uncoupling protein (UCP1), on variation in human obesity status and/or quantitative traits related to obesity in Mexican Americans from Starr County, Texas. The Trp64Arg polymorphism within β3AR was typed in 820 random individuals and 240 pedigrees (N = 2,044). The Arg allele frequency was significantly greater in obese versus non-obese individuals (0.20 versus 0. 15, respectively). In addition, within the random sample, the Arg allele was associated with significantly greater body weight (p = 0.031) and body mass index (BMI, p = 0.008) than the Trp allele. In the family sample, the Trp64Arg locus was also linked to percent fat (p = 0.045) but not to body weight or BMI. No linkage between obesity, diabetes, hypertension, or gallbladder disease and the Trp64Arg mutation was observed in families using affected sib pair linkage analysis or the transmission disequilibrium test. Microsatellite markers proximate to the remaining seven genes were typed in 302 individuals from 59 families. Sib pair linkage analysis provided evidence for linkage between obesity and NPY within affected sibling pairs (p = 0.042; n = 170 pairs). NPY was also linked to weight (p = 0.020), abdominal circumference (p = 0.031), hip circumference (p = 0.012), DBP (p ≤ 0.005), and a composite measure of body mass/fat (p ≤ 0.048) in all sibling pairs (n = 545 pairs). Additionally, LEP was linked to waist/hip ratio (p ≤ 0.009), total cholesterol (p ≤ 0.030), and HDL cholesterol (p ≤ 0.026), and LEPR was linked to fasting blood glucose (p ≤ 0.018) and DBP (p ≤ 0.003). Subsequent to the linkage analyses, the NPY gene was sequenced and eight variant sites identified. Two variant sites (-880I/D and 69I/D) were typed in a random sample of 914 individuals. The 880I/D variant was significantly associated with waist/hip ratio (p = 0.035) in the entire sample (N = 914) and with BMI (p = 0. 031), abdominal circumference (p = 0.044), and waist/hip ratio (p = 0.041) in a non-obese subsample (BW < 30 kg/m2, n = 594). The 69I/D variant was a rare mutation observed in only one pedigree and was not associated with obesity or body size/mass within this pedigree. Results of this study indicate that variation at or near β3AR, LEP, LEPR, and NPY may exert effects which increase obesity susceptibility and influence obesity-related measures in this population. ^

The effect of exposure to antibiotics on incidence and spontaneous clearance of childhood Helicobacter pylori infection

It is claimed often in the H. pylori literature that spontaneous clearance (infection loss without attempts to treat) is uncommon, though little evidence supports this claim. Emerging evidence suggests that spontaneous clearance may be frequent in young children; however, factors that determine persistence of untreated H. pylori infection in childhood are not well understood. The author hypothesized that antibiotics taken for common infections cause spontaneous clearance of H. pylori infection in children. The Pasitos Cohort Study (19982005) investigated predictors of acquisition and persistence of H. pylori infection in children from El Paso, Texas, and Juarez, Mexico, enrolled prenatally at maternal-child clinics. Children were screened for infection at target intervals of 6 months from 6-84 months of age by the 13C-urea breath test corrected for body-size-dependent variation in CO2 production. This dissertation aimed to estimate the risk of spontaneous clearance at the next test following an initial detected H. pylori infection (first detected clearance), estimate the effect of antibiotic exposure on the risk of first detected clearance (risk difference), and estimate the effect of antibiotic exposure on the rate of first detected infection (rate ratio). Data on infection status and medication history were available for 608 children followed for a mean of 3.5 years. Among 265 subjects with a first detected infection, 218 had a subsequent test, and among them, the risk of first detected clearance was 68% (95% CI: 61-74%). Children who took antibiotics during the interval between first detected infection and next test had an increased probability (risk difference of 10 percentage points) of a first detected clearance. However, there was also a similar effect of average antibiotic use >0 courses across all intervals preceding the next test. Average antibiotic exposure across all intervals preceding the first detected infection appeared to have a much stronger protective effect than interval/specific exposure when estimating incidence rate ratios (0.45 vs. 1.0). Incidental antibiotic exposure appears to influence the acquisition and duration of childhood H. pylori infection, however, given that many exposed children acquired the infection and many unexposed children cleared the infection, antibiotic exposure does not explain all infection events. ^

The relationship between food preparation time, time spent grocery shopping, and BMI

Recent data have shown that the percentage of time spent preparing food has decreased during the past few years, and little information is know about how much time people spend grocery shopping. Food that is pre-prepared is often higher in calories and fat compared to foods prepared at home from scratch. It has been suggested that, because of the higher energy and total fat levels, increased consumption of pre-prepared foods compared to home-cooked meals can lead to weight gain, which in turn can lead to obesity. Nevertheless, to date no study has examined this relationship. The purpose of this study is to determine (i) the association between adult body mass index (BMI) and the time spent preparing meals, and (ii) the association between adult BMI and time spent shopping for food. Data on food habits and body size were collected with a self-report survey of ethnically diverse adults between the ages of 17 and 70 at a large university. The survey was used to recruit people to participate in nutrition or appetite studies. Among other data, the survey collected demographic data (gender, race/ethnicity), minutes per week spent in preparing meals and minutes per week spent grocery shopping. Height and weight were self-reported and used to calculate BMI. The study population consisted of 689 subjects, of which 276 were male and 413 were female. The mean age was 23.5 years, with a median age of 21 years. The fraction of subjects with BMI less than 24.9 was 65%, between 25 and 29.9 was 26%, and 30 or greater was 9%. Analysis of variation was used to examine associations between food preparation time and BMI. ^ The results of the study showed that there were no significant statistical association between adult healthy weight, overweight and obesity with either food preparation time and grocery shopping time. Of those in the sample who reported preparing food, the mean food preparation time per week for the healthy weight, overweight, and obese groups were 12.8 minutes, 12.3 minutes, and 11.6 minutes respectively. Similarly, the mean weekly grocery shopping for healthy, overweight, and obese groups were 60.3 minutes per week (8.6min./day), 61.4 minutes (8.8min./day), and 57.3 minutes (8.2min./day), respectively. Since this study was conducted through a University campus, it is assumed that most of the sample was students, and a percentage might have been utilizing meal plans on campus, and thus, would have reported little meal preparation or grocery shopping time. Further research should examine the relationships between meal preparation time and time spent shopping for food in a sample that is more representative of the general public. In addition, most people spent very little time preparing food, and thus, health promotion programs for this population need to focus on strategies for preparing quick meals or eating in restaurants/cafeterias. ^

Genetic variability and the hypothalamic control of energy balance

Background. Obesity is a major health problem throughout the industrialized world. Despite numerous attempts to curtail the rapid growth of obesity, its incidence continues to rise. Therefore, it is crucial to better understand the etiology of obesity beyond the concept of energy balance.^ Aims. The first aim of this study was to first investigate the relationship between eating behaviors and body size. The second goal was to identify genetic variation associated with eating behaviors. Thirdly, this study aimed to examine the joint relationships between eating behavior, body size and genetic variation.^ Methods. This study utilized baseline data ascertained in young adults from the Training Interventions and Genetics of Exercise (TIGER) Study. Variables assessed included eating behavior (Emotional Eating Scale, Eating Attitudes Test-26, and the Block98 Food Frequency Questionnaire), body size (body mass index, waist and hip circumference, waist/hip ratio, and percent body fat), genetic variation in genes implicated related to the hypothalamic control of energy balance, and appropriate covariates (age, gender, race/ethnicity, smoking status, and physical activity. For the genetic association analyses, genotypes were collapsed by minor allele frequency, and haplotypes were estimated for each gene. Additionally, Bayesian networks were constructed in order to determine the relationships between genetic variation, eating behavior and body size.^ Results. We report that the EAT-26 score, Caloric intake, percent fat, fiber intake, HEAT index, and daily servings of vegetables, meats, grains, and fats were significantly associated with at least one body size measure. Multiple SNPs in 17 genes and haplotypes from 12 genes were tested for their association with body size. Variation within both DRD4 and HTR2A was found to be associated with EAT-26 score. In addition, variation in the ghrelin gene (GHRL) was significantly associated with daily Caloric intake. A significant interaction between daily servings of grains and the HEAT index and variation within the leptin receptor gene (LEPR) was shown to influence body size.^ Conclusion. This study has shown that there is a substantial genetic component to eating behavior and that genetic variation interacts with eating behavior to influence body size.^

Concordance between medical records and personal interview in ascertaining breast cancer and diabetes status: Analysis of the south Texas women's health project

Accurate ascertainment of risk factors and disease status is vital in public health research for proper classification of research subjects. The two most common ways of obtaining this data is by self-report and review of medical records (MRs). South Texas Women’s Health Project was a case-control study looking at interrelationships between hormones, diet, and body size and breast cancer among Hispanic women 30-79 years of age. History of breast cancer, diabetes mellitus (DM) and use of DM medications was ascertained from a personal interview. At the time of interview, the subject identified her major health care providers and signed the medical records release form, which was sent to the designated providers. The MRs were reviewed to confirm information obtained from the interview.^ Aim of this study was to determine the sensitivity and specificity between MRs and personal interview in diagnosis of breast cancer, DM and DM treatment. We also wanted to assess how successful our low-cost approach was in obtaining pertinent MRs and what factors influenced the quality of MR or interview data. Study sample was 721 women with both self-report and MR data available by June 2007. Overall response rate for MR requests was 74.5%. MRs were 80.9% sensitive and 100% specific in confirming breast cancer status. Prevalence of DM was 22.7% from the interviews and 16% from MRs. MRs did not provide definite information about DM status of 53.6% subjects. Sensitivity and specificity of MRs for DM status was 88.9% and 90.4% respectively. Disagreement on DM status from the two sources was seen in 15.9% subjects. This discordance was more common among older subjects, those who were married and were predominantly Spanish speaking. Income and level of education did not have a statistically significantly association with this disagreement.^ Both self-report and MRs underestimate the prevalence of DM. Relying solely on MRs leads to greater misclassification than relying on self-report data. MRs have good to excellent specificity and thus serve as a good tool to confirm information obtained from self-report. Self-report and MRs should be used in a complementary manner for accurate assessment of DM and breast cancer status.^

The Choosing Healthy Options of Starches (CHOOS) diet and dietary intake self-monitoring for weight loss among adolescent females

Previous research has shown dietary intake self-monitoring, and culturally tailored weight loss interventions to be effective tools for weight loss. Technology can be used to tailor weight loss interventions to better suit adolescents. There is a lack of research to date on the use of personal digital assistants (PDAs) to self-monitor dietary intake among adolescents. The objective of this study was to determine the difference in dietary intake self-monitoring frequency between using a Personal Digital Assistant (PDA) or paper logs as a diet diary in obese adolescent females; and to describe differences in diet adherence, as well as changes in body size and self-efficacy to resist eating. We hypothesized dietary intake self-monitoring frequency would be greater during PDA use than during paper log use. This study was a randomized crossover trial. Participants recorded their diet for 4 weeks: 2 weeks on a PDA and 2 weeks on paper logs. Thirty-four obese females ages 12-20 were recruited for participation. Thirty were included in analyses. Participants recorded more entries/day while using the paper logs (4.10 entries/day ± 0.63) than while using the PDA (3.01 entries/day ±0.75) (p<0.001). Significantly more meals and snacks were skipped during paper log use (0.81/day ± 0.65) than during PDA use (0.23/day ± 0.22) (p=0.011). Changes in body size (BMI, weight, and waist circumference) and self-efficacy to resist eating did not differ significantly between PDA and paper log use. When compared to paper logs, participants felt the PDA was more convenient (p=0.020), looked forward to using the PDA more (p=0.008), and would rather continue using the PDA than the paper logs (p=0.020). The findings of this study indicate use of a PDA as a dietary intake self-monitoring tool among adolescents would not result in increased dietary intake self-monitoring to aid in weight loss. Use of paper logs would result in greater data returned to clinicians, though use of PDAs would likely get adolescents more excited about adhering to recommendations to record their diet. Future research should look at updated communication devices, such as cell phones and other PDAs with additional features, and the role they can play in increasing dietary intake self-monitoring among adolescents.^

Targeted Deletion Of Functionally Validated Enhancers Defines Their Role in Mouse Limb Development

Transcriptional enhancers are genomic DNA sequences that contain clustered transcription factor (TF) binding sites. When combinations of TFs bind to enhancer sequences they act together with basal transcriptional machinery to regulate the timing, location and quantity of gene transcription. Elucidating the genetic mechanisms responsible for differential gene expression, including the role of enhancers, during embryological and postnatal development is essential to an understanding of evolutionary processes and disease etiology. Numerous methods are in use to identify and characterize enhancers. Several high-throughput methods generate large datasets of enhancer sequences with putative roles in embryonic development. However, few enhancers have been deleted from the genome to determine their roles in the development of specific structures, such as the limb. Manipulation of enhancers at their endogenous loci, such as the deletion of such elements, leads to a better understanding of the regulatory interactions, rules and complexities that contribute to faithful and variant gene transcription – the molecular genetic substrate of evolution and disease. To understand the endogenous roles of two distinct enhancers known to be active in the mouse embryo limb bud we deleted them from the mouse genome. I hypothesized that deletion of these enhancers would lead to aberrant limb development. The enhancers were selected because of their association with p300, a protein associated with active transcription, and because the human enhancer sequences drive distinct lacZ expression patterns in limb buds of embryonic day (E) 11.5 transgenic mice. To confirm that the orthologous mouse enhancers, mouse 280 and 1442 (M280 and M1442, respectively), regulate expression in the developing limb we generated stable transgenic lines, and examined lacZ expression. In M280-lacZ mice, expression was detected in E11.5 fore- and hindlimbs in a region that corresponds to digits II-IV. M1442-lacZ mice exhibited lacZ expression in posterior and anterior margins of the fore- and hindlimbs that overlapped with digits I and V and several wrist bones. We generated mice lacking the M280 and M1442 enhancers by gene targeting. Intercrosses between M280 -/+ and M1442 -/+, respectively, generated M280 and M1442 null mice, which are born at expected Mendelian ratios and manifest no gross limb malformations. Quantitative real-time PCR of mutant E11.5 limb buds indicated that significant changes in transcriptional output of enhancer-proximal genes accompanied the deletion of both M280 and M1442. In neonatal null mice we observed that all limb bones are present in their expected positions, an observation also confirmed by histology of E18.5 distal limbs. Fine-scale measurement of E18.5 digit bone lengths found no differences between mutant and control embryos. Furthermore, when the developmental progression of cartilaginous elements was analyzed in M280 and M1442 embryos from E13.5-E15.5, transient development defects were not detected. These results demonstrate that M280 and M1442 are not required for mouse limb development. Though M280 is not required for embryonic limb development it is required for the development and/or maintenance of body size – adult M280 mice are significantly smaller than control littermates. These studies highlight the importance of experiments that manipulate enhancers in situ to understand their contribution to development.