Nonlinear Relationship between Birth Weight and Visceral Fat in Adolescents.

OBJECTIVE: To determine the association of birth weight with abdominal fat distribution and markers known to increase risk for cardiovascular disease and type 2 diabetes in adolescents. STUDY DESIGN: In 575 adolescents aged 14-18 years (52% female, 46% black), birth weight was obtained by parental recall. Fasting blood samples were measured for glucose, insulin, lipids, adiponectin, leptin, and C-reactive protein. Subcutaneous abdominal adipose tissue and visceral adipose tissue were assessed by magnetic resonance imaging. RESULTS: When we compared markers of cardiometabolic risk across tertiles of birth weight, adjusting for age, sex, race, Tanner stage, physical activity, socioeconomic status, and body mass index, there were significant U-shaped trends for homeostasis model assessment of insulin resistance, leptin, and visceral adipose tissue (all Pquadratic < .05). A significant linear downward trend across tertiles of birth weight was observed for triglycerides (Plinear = .03). There were no differences in fasting glucose, blood pressure, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, adiponectin, C-reactive protein, or subcutaneous abdominal adipose tissue across tertiles of birth weight. CONCLUSIONS: Our data suggest that both low and high birth weights are associated with greater visceral adiposity and biomarkers implicated in insulin resistance and inflammation in adolescents.

More physically active and leaner adolescents have higher energy intake.

OBJECTIVE: To test whether youths who engage in vigorous physical activity are more likely to have lean bodies while ingesting relatively large amounts of energy. For this purpose, we studied the associations of both physical activity and adiposity with energy intake in adolescents. STUDY DESIGN: The study subjects were adolescents who participated in 1 of 2 cross-sectional studies, the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study (n = 1450; mean age, 14.6 years) or the European Youth Heart Study (EYHS; n = 321; mean age, 15.6 years). Physical activity was measured by accelerometry, and energy intake was measured by 24-hour recall. In the HELENA study, body composition was assessed by 2 or more of the following methods: skinfold thickness, bioelectrical impedance analysis, plus dual-energy X-ray absorptiometry or air-displacement plethysmography in a subsample. In the EYHS, body composition was assessed by skinfold thickness. RESULTS: Fat mass was inversely associated with energy intake in both studies and using 4 different measurement methods (P ≤ .006). Overall, fat-free mass was positively associated with energy intake in both studies, yet the results were not consistent across measurement methods in the HELENA study. Vigorous physical activity in the HELENA study (P < .05) and moderate physical activity in the EYHS (P < .01) were positively associated with energy intake. Overall, results remained unchanged after adjustment for potential confounding factors, after mutual adjustment among the main exposures (physical activity and fat mass), and after the elimination of obese subjects, who might tend to underreport energy intake, from the analyses. CONCLUSION: Our data are consistent with the hypothesis that more physically active and leaner adolescents have higher energy intake than less active adolescents with larger amounts of fat mass.

A genome-wide methylation study of severe vitamin D deficiency in African American adolescents.

OBJECTIVES: To test the hypothesis that changes in DNA methylation are involved in vitamin D deficiency-related immune cell regulation using an unbiased genome-wide approach combined with a genomic and epigenomic integrative approach. STUDY DESIGN: We performed a genome-wide methylation scan using the Illumina HumanMethylation 27 BeadChip on leukocyte DNA of 11 cases of vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] ≤ 25 nmol/L) and 11 age-matched controls ([25(OH)D] > 75 nmol/L); the subjects were African American normal-weight (body mass index <85th percentile) males aged 14-19 years. The Limma package was used to analyze each CpG site for differential methylation between cases and controls. To correct for multiple testing, the set of raw P values were converted to false discovery rates (FDRs). We also compared our findings with the recent data from Genome-Wide Association Studies of circulating 25(OH)D levels and then performed a permutation test to examine whether the "double hit" genes were randomly enriched. RESULTS: A total of 79 CpG sites achieved raw P < .001. Of the 79 CpG sites, 2 CpG sites survived multiple testing: cg16317961 (raw P = 3.5 × 10(-6), FDR = 0.078, in MAPRE2) and cg04623955 (raw P = 5.9 × 10(-6), FDR = 0.078, in DIO3). Furthermore, 3 out of the 4 genes previously identified in the 2 Genome-Wide Association Studies were also significant at the methylation level (DHCR7: cg07487535, P = .015 and cg10763288, P = .017; CYP2R1: cg25454890, P = .040; CYP24A1: cg18956481, P = .022), reflecting significant enrichment (P = .0098). CONCLUSION: Severe vitamin D deficiency is associated with methylation changes in leukocyte DNA. The genomic and epigenomic approach reinforce the crucial roles played by the DHCR7, CYP2R1, and CYP24A1 genes in vitamin D metabolism.

Adolescent obesity, bone mass, and cardiometabolic risk factors.

OBJECTIVE: To compare bone mass between overweight adolescents with and without cardiometabolic risk factors (CMR). Associations of bone mass with CMR and adiposity were also determined. STUDY DESIGN: Adolescents (aged 14 to 18 years) who were overweight were classified as healthy (n = 55), having one CMR (1CMR; n = 46), or having two or more CMR (≥2CMR; n = 42). CMRs were measured with standard methods and defined according to pediatric definitions of metabolic syndrome. Total body bone mass, fat mass, and fat-free soft tissue mass were measured with dual-energy X-ray absorptiometry. Visceral adipose tissue and subcutaneous abdominal adipose tissue were assessed with magnetic resonance imaging. RESULTS: After controlling for age, sex, race, height, and fat-free soft tissue mass, the healthy group had 5.4% and 6.3% greater bone mass than the 1CMR and ≥2CMR groups, respectively (both P values <.04). With multiple linear regression, adjusting for the same co-variates, visceral adipose tissue (ß = -0.22), waist circumference (ß = -0.23), homeostasis model assessment of insulin resistance (ß = -0.23), and high-density lipoprotein cholesterol level (ß = 0.22) were revealed to be associated with bone mass (all P values <.04). There was a trend toward a significant inverse association between bone mass and fasting glucose level (P = .056). No relations were found between bone mass and fat mass, subcutaneous abdominal adipose tissue, blood pressure, or triglyceride level. CONCLUSION: Being overweight with metabolic abnormalities, particularly insulin resistance, low high-density lipoprotein cholesterol level, and visceral adiposity, may adversely influence adolescent bone mass.

Leukocyte telomere length in healthy Caucasian and African-American adolescents: relationships with race, sex, adiposity, adipokines, and physical activity.

OBJECTIVE: To examine the relationships of race, sex, adiposity, adipokines, and physical activity to telomere length in adolescents. STUDY DESIGN: Leukocyte telomere length (T/S ratio) was assessed cross-sectionally in 667 adolescents (aged 14-18 years; 48% African-Americans; 51% girls) using a quantitative polymerase chain reaction method. Generalized estimating equations analyses were performed. RESULTS: Telomere length was greater in the African-American adolescents than in the Caucasian adolescents (age- and sex-adjusted T/S ratio ± SE, 1.32 ± 0.01 vs 1.27 ± 0.01: P = .014) and greater in girls than in boys (age- and race-adjusted T/S ratio ± SE, 1.31 ± 0.01 vs 1.27 ± 0.01; P = .007). None of the adiposity or adipokine measures explained a significant proportion of the variance in telomere length. Vigorous physical activity was positively associated with telomere length (adjusted R(2) = 0.019; P = .009) and accounted for 1.9% of the total variance only in girls. CONCLUSIONS: This study, conducted in a biracial adolescent cohort, demonstrated that (1) race and sex differences in telomere length have already emerged during adolescence; (2) adiposity and adipokines are not associated with telomere length at this age; and (3) the antiaging effect of vigorous physical activity may begin in youth, especially in girls.

Common variants near melanocortin 4 receptor are associated with general and visceral adiposity in European- and African-American youth.

OBJECTIVE: Recent genome-wide association studies found common variants near the melanocortin 4 receptor gene associated with obesity. This study aimed to assess the influence of the identified single nucleotide polymorphisms rs17782313 and rs17700633 on general and visceral adiposity in European- and African-American youth. STUDY DESIGN: In 1890 youth (49.1% European-American, 45.6% male, mean age 16.7 years), we examined the associations of the rs17782313 and rs17700633 with anthropometry, percent body fat, visceral adipose tissue, and subcutaneous abdominal adipose tissue. Interaction of the single nucleotide polymorphisms with ethnicity or sex was investigated and haplotype analyses conducted. RESULTS: Rs17782313 was significantly associated with weight (P = .02) and waist circumference (P = .03) in all subjects and with body mass index (P = .002) in females. In females rs17700633 was significantly associated with percent body fat (P = .001), visceral adipose tissue (P < .001), and subcutaneous abdominal adipose tissue (P < .001). Rs17700633 was significantly associated with fasting insulin and homeostasis model assessment, but the significance attenuated after adjustment for percent body fat. These findings were confirmed by haplotype analysis. No significant interactions of the variants with ethnicity were found for any of these phenotypes. CONCLUSIONS: The relatively large effect of these common variants near melanocortin 4 receptor on general and visceral adiposity in childhood, especially in girls, could prove helpful in elucidating the molecular mechanisms underlying the development of obesity in early life.

Evidence based physical activity for school-age youth.

OBJECTIVES: To review the effects of physical activity on health and behavior outcomes and develop evidence-based recommendations for physical activity in youth. STUDY DESIGN: A systematic literature review identified 850 articles; additional papers were identified by the expert panelists. Articles in the identified outcome areas were reviewed, evaluated and summarized by an expert panelist. The strength of the evidence, conclusions, key issues, and gaps in the evidence were abstracted in a standardized format and presented and discussed by panelists and organizational representatives. RESULTS: Most intervention studies used supervised programs of moderate to vigorous physical activity of 30 to 45 minutes duration 3 to 5 days per week. The panel believed that a greater amount of physical activity would be necessary to achieve similar beneficial effects on health and behavioral outcomes in ordinary daily circumstances (typically intermittent and unsupervised activity). CONCLUSION: School-age youth should participate daily in 60 minutes or more of moderate to vigorous physical activity that is developmentally appropriate, enjoyable, and involves a variety of activities.

Relations of fatness and fitness to fasting insulin in black and white adolescents.

OBJECTIVE: To determine in black and white youths the degree to which fatness and cardiovascular fitness (CVF) explained independent proportions of the variance in fasting insulin concentrations. STUDY DESIGN: Youths 14 to 18 years of age (n = 278) were studied. Insulin was measured after a 12-hour fast. Percent body fat (%BF) was measured with dual-energy x-ray absorptiometry. CVF was determined with a multistage treadmill test. RESULTS: Girls had higher %BF and lower CVF than boys. Whites were higher in CVF than blacks. There was a race by sex interaction for fasting insulin concentration, such that black girls had the highest and white girls had the lowest concentrations. When %BF and CVF was controlled statistically, this interaction was no longer significant. Multiple regression models that controlled for race, sex, and their interaction showed that (1) both higher %BF and lower CVF were significantly associated with higher insulin concentrations; (2) there were significant interactions with sex, such that the deleterious effects of low CVF and high %BF were greater in boys than in girls; (3) there was a significant CVF-%BF interaction, such that youths who were both fit and lean had especially low insulin concentrations; and (4) sex-specific regressions showed that both %BF and CVF explained significant independent proportion of the insulin variance for the boys but that only %BF did so for the girls. CONCLUSIONS: Interventions to prevent hyperinsulinemia in youths should be designed both to minimize fatness and maximize CVF.

Hemostatic and inflammatory markers in obese youths: effects of exercise and adiposity.

OBJECTIVES: To determine the relation of hemostatic markers to cardiovascular fitness and adiposity and the effect of physical training (PT) on these markers. STUDY DESIGN: Seventy-four obese teenagers were randomly assigned to 8 months of lifestyle education (LSE), LSE plus moderate-intensity PT, or LSE plus high-intensity PT. Measures included fibrinogen, plasminogen activator inhibitor-1 (PAI-1), D-dimer, C-reactive protein (CRP), fitness, percent body fat (%BF), and visceral adiposity (VAT). RESULTS: At baseline, fibrinogen and CRP were significantly correlated with %BF and VAT (0.27