Previous studies estimated critical periods of childhood body mass index (BMI) growth and linked these events to adult adiposity and cardiovascular health. We expand upon both results to link childhood BMI growth patterns with adult blood pressure. Data from male and female participants in the Fels Longitudinal Study were used to estimate childhood BMI growth curves, from which we isolate ages of childhood BMI divergence based upon adult BMI and blood pressure measurements. Repeated measure analysis of variances models were used to estimate BMI growth curves from ages 2 to 17.5 based on both adult BMI (< 25 kg/m2 or ≥ 25 kg/m2) and adult blood pressure (< 120 mmHg or ≥ 120 mmHg for systolic blood pressure; < 80 mmHg or ≥ 80 mm Hg for diastolic blood pressure). Participants with lower bodyweight throughout childhood had lower systolic and diastolic blood pressures in early adulthood. Any relationships between childhood adiposity and adult bodyweight and blood pressure disappeared by age 60. These results were independent of adult BMI and were observed in both men and women. Increased adult blood pressure has its genesis in part from increased childhood BMI.

Meta-analysis of genome-wide association studies (GWAS) has become a useful tool to identify genetic variants that are associated with complex human diseases. To control spurious associations between genetic variants and disease that are caused by population stratification, double genomic control (GC) correction for population stratification in meta-analysis for GWAS has been implemented in the software METAL and GWAMA and is widely used by investigators. In this research, we conducted extensive simulation studies to evaluate the double GC correction method in meta-analysis and compared the performance of the double GC correction with that of a principal components analysis (PCA) correction method in meta-analysis. Results show that when the data consist of population stratification, using double GC correction method can have inflated type I error rates at a marker with significant allele frequency differentiation in the subpopulations (such as caused by recent strong selection). On the other hand, the PCA correction method can control type I error rates well and has much higher power in meta-analysis compared to the double GC correction method, even though in the situation that the casual marker does not have significant allele frequency difference between the subpopulations. We applied the double GC correction and PCA correction to meta-analysis of GWAS for two real datasets from the Atherosclerosis Risk in Communities (ARIC) project and the Multi-Ethnic Study of Atherosclerosis (MESA) project. The results also suggest that PCA correction is more effective than the double GC correction in meta-analysis.

Objective

The metabolic syndrome (MetS) is a cluster of clinical indices that signals increased risk for cardiovascular disease and Type 2 diabetes. The diagnosis of MetS is typically based on cut-off points for various components, e.g. waist circumference and blood pressure. Because current MetS criteria result in racial/ethnic discrepancies, our goal was to use confirmatory factor analysis to delineate differential contributions to MetS by sub-group.

Research Design and Methods

Using 1999–2010 data from the National Health and Nutrition Examination Survey (NHANES), we performed a confirmatory factor analysis of a single MetS factor that allowed differential loadings across sex and race/ethnicity, resulting in a continuous MetS risk score that is sex and race/ethnicity-specific.

Results

Loadings to the MetS score differed by racial/ethnic and gender subgroup with respect to triglycerides and HDL-cholesterol. ROC-curve analysis revealed high area-under-the-curve concordance with MetS by traditional criteria (0.96), and with elevations in MetS-associated risk markers, including high-sensitivity C-reactive protein (0.71), uric acid (0.75) and fasting insulin (0.82). Using a cut off for this score derived from ROC-curve analysis, the MetS risk score exhibited increased sensitivity for predicting elevations in ≥2 of these risk markers as compared with traditional pediatric MetS criteria.

Conclusions

The equations from this sex- and race/ethnicity-specific analysis provide a clinically-accessible and interpretable continuous measure of MetS that can be used to identify children at higher risk for developing adult diseases related to MetS, who could then be targeted for intervention. These equations also provide a powerful new outcome for use in childhood obesity and MetS research.

Evidence suggests that when carefully implemented, health information technologies (HIT) have a positive impact on behavior, as well as operational, process, and clinical outcomes. Recent economic stimulus initiatives have prompted unprecedented federal investment in HIT. Despite strong interest from the healthcare delivery community to achieve ‘meaningful use’ of HIT within a relatively short time frame, few best-practice implementation methodologies have been described. Herein we outline HIT implementation strategies at an academic health center with an office of clinical transformation. Seven percent of the medical center's information technology budget was dedicated to the Office of Clinical Transformation, and successful conversion of 1491 physicians to electronic-based documentation was accomplished. This paper outlines the process re-design, end-user adoption, and practice transformation strategies that resulted in a 99.7% adoption rate within 6 months of the introduction of digital documentation.

Objectives

Several studies have shown that causes of adult hypertension arise in childhood, and obesity may be a potential cause or at least a mitigating factor in this development. Body mass index is a well studied obesity metric, yet other potential adiposity measures such as percent body fat and waist circumference have been somewhat less considered. The purpose of this study is to determine associations between these alternative serial childhood adiposity measures and adulthood blood pressure.

Methods

Measurements from participants in the Fels Longitudinal Study were used to summarize childhood adiposity, represented by childhood measurements of percent body fat and height-adjusted waist circumference. These subjects also provided systolic and diastolic blood pressure as adults. Childhood adiposity levels were categorized as high or low as compared to the respective upper quartile, and associations with adult blood pressure were measured using Poisson regression to estimate the number of expected occurrences of elevated adiposity during childhood. Adult lifestyle covariates and adiposity were accounted for using multiple linear regression.

Results

Summary indices of the childhood adiposity measures were significantly associated with both adult blood pressure metrics in men and women, though some of these associations were altered or reduced in the presence of adult lifestyle characteristics and adult adiposity measures.

Conclusions

Childhood measures of percent body fat and height-adjusted waist circumference have an effect on adult blood pressure, though the effect can be mitigated by adult lifestyles.

Objectives

To ascertain the influence of such a prolonged juvenile state on delaying the onset of the metabolic syndrome, cardiovascular disease (CVD), and type 2 diabetes mellitus (T2DM) later in life.

Study design

We define prolongation of a juvenile state as a retarded tempo of growth, determined by the timing of peak height velocity in each subject and relate the retarded tempo of growth to metabolic syndrome, cardiovascular disease (CVD), and type 2 diabetes mellitus (T2DM) later in life using serial data of 237 study participants (119 men and 118 women) participants enrolled in the Fels Longitudinal study.

Results

Children who matured early tended to have greater BMI, waist circumference, percent of body fat and were more likely to have adverse cardiovascular risk profiles than children who matured late. The differences in these risk factors between early and late maturers were significant for percent body fat, fasting plasma triglycerides, and fasting plasma insulin.

Conclusions

The analyses disclosed a clear separation between early and late maturers in the appearance of these risk factors in young adulthood.

Objective

We tested sex, race, and age differences in the patterning of visceral adipose tissue (VAT) and subcutaneous adipose tissue.

Research Methods and Procedures

Contiguous 1-cm-thick magnetic resonance (MR) images of the abdomen were collected from 820 African-American and white adults. Repeated-measures ANOVA was used to examine the effects of image location, sex, race, and age (≥50 vs. <50 years) on adipose tissue areas. Maximum VAT area was identified for each subject from the raw data.

Results

Compared to women, men had greater total VAT volume (p < 0.0001), and their maximum VAT area occurred higher in the abdomen (p < 0.0001). Among white men, maximim VAT area most frequently occurred 5 to 10 cm above L4-L5, whereas in the other groups, maximim VAT area most frequently occurred 1 to 4 cm above L4-L5 (p < 0.0001). African-American men had greater total VAT volume than African-American women (p < 0.01), but this sex difference was only significant using single images cranial to L4-L5 + 2 cm. Age-related increases in VAT tended to be greatest 5 to 10 cm above L4-L5 in men and near L4-L5 in women.

Discussion

A single MR image 5 to 10 cm above L4-L5 may allow more accurate conclusions than the L4-L5 image regarding group differences in visceral adiposity.

Background

Despite the recognition that central obesity plays a critical role in chronic disease, few large-scale imaging studies have documented human variation in abdominal adipose tissue patterning.

Objective

We aimed to compare the associations between abdominal subcutaneous adipose tissue (ASAT) and visceral abdominal tissue (VAT), which were measured at different locations across the abdomen, and the presence of the metabolic syndrome (MS; National Cholesterol Education Program Adult Treatment Panel III definition) and individual cardiometabolic risk factors.

Design

This study included 713 non-Hispanic whites aged 18–86 y, in whom VAT and ASAT were assessed by using multiple-image magnetic resonance imaging. The anatomical position of the magnetic resonance image containing the maximum VAT area for each subject was used as a measure of VAT patterning. Multivariate linear and logistic regression analyses were used to examine the relation of VAT, ASAT, and VAT patterning to cardiometabolic risk.

Results

VAT mass was a stronger predictor of the MS than was ASAT mass, but ASAT mass (and other measures of subcutaneous adiposity) had signification interactions with VAT mass, whereby elevated ASAT reduced the probability of MS among men with high VAT (P = 0.0008). There was variation across image locations in the association of VAT area with the MS in men, and magnetic resonance images located 4–8 cm above L4–L5 provided the strongest correlations between VAT area and cardiometabolic risk factors. Subjects whose maximum VAT area was higher in the abdomen had higher LDL-cholesterol concentrations (R2 = 0.07, P = 0.0001), independent of age and adiposity.

Conclusion

Further studies are needed to confirm the effects of VAT patterning on cardiometabolic risk.

Despite significant progress in understanding the mechanisms by which the prenatal/maternal environment can alter development and adult health, genetic influences on normal variation in growth are little understood. This work examines genetic and nongenetic contributions to body weight and weight change during infancy and the relationships between weight change and adult body composition. The dataset included 501 white infants in 164 nuclear and extended families in the Fels Longitudinal Study, each with 10 serial measures of weight from birth to age 3 years and 232 with body composition data in mid-adulthood. Herit-ability and covariate effects on weight and weight z-score change from birth to 2 years of age were estimated using a maximum likelihood variance decomposition method. Additive genetic effects explained a high proportion of the variance in infant weight status (h2 = 0.61–0.95), and change in weight z-score (h2 = 0.56–0.82). Covariate effects explained 27% of the phenotypic variance at 0–1 month of age and declined in effect to 6.9% of phenotypic variance by 36 months. Significant sex, gestational age, birth order, birth year, and maternal body mass index effects were also identified. For both sexes, a significant increase in weight z-score (>2 SD units) (upward centile crossing) was associated with greater adulthood stature, fat mass, and percent body fat than decrease or stability in weight z-score. Understanding genetic influences on growth rate in a well-nourished, nutritionally stable population may help us interpret the causes and consequences of centile crossing in nutritionally compromised contexts.

The genetic influences on bone mass likely change throughout the life span, but most genetic studies of bone mass regulation have focused on adults. There is, however, a growing awareness of the importance of genes influencing the acquisition of bone mass during childhood on lifelong bone health. The present investigation examines genetic influences on childhood bone mass by estimating the residual heritabilities of different measures of second metacarpal bone mass in a sample of 600 10-year-old participants from 144 families in the Fels Longitudinal Study. Bivariate quantitative genetic analyses were conducted to estimate genetic correlations between cortical bone mass measures, and measures of bone growth and development. Using a maximum likelihood-based variance components method for pedigree data, we found a residual heritability estimate of 0.71 for second metacarpal cortical index. Residual heritability estimates for individual measures of cortical bone (e.g., lateral cortical thickness, medial cortical thickness) ranged from 0.47 to 0.58, at this pre-pubertal childhood age. Low genetic correlations were found between cortical bone measures and both bone length and skeletal age. However, after Bonferonni adjustment for multiple testing, ρG was not significantly different from 0 for any of these pairs of traits. Results of this investigation provide evidence of significant genetic control over bone mass largely independent of maturation while bones are actively growing and before rapid accrual of bone that typically occurs during puberty.