The Impact of Whole Egg Consumption on Bone Accrual in Healthy Children: A Randomized Controlled Trial.

Dietary interventions designed to examine the role of nutrition on childhood bone accrual have often focused on the role of individual micronutrients (eg, calcium, vitamin D, and zinc) and macronutrients (eg, protein). The osteogenic benefits of whole foods, such as eggs, are not well understood despite eggs being a source of high-quality nutrients and bioactive compounds known to positively influence bone. A significant positive cross-sectional association between whole egg consumption and tibia cortical bone mass has recently been shown in young children; however, randomized controlled trials (RCTs) have not been conducted. This study is a double-blind RCT in male and female children ages 9-13 years of different ancestries, designed to determine if consuming food products with whole eggs (equivalent to 8-10 eggs/wk) versus foods with milk or gelatin (placebo) over a 9-month period will improve measures of bone strength. Total body less head (TBLH) and lumbar spine bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed using dual-energy X-ray absorptiometry (DXA). DXA Z-scores were computed using published pediatric growth charts and were adjusted for height-for-age Z-score (HAZ). Mid-tibia cortical volumetric BMD, BMC, cortical area, total bone area, cortical thickness, and strength strain index were measured using peripheral quantitative computed tomography. Overall, there were no significant intervention effects for any bone outcomes. The increase in spine BMCHAZ Z-score in the egg group versus the gelatin group approached significance (p = 0.07). Significant time effects in TBLH aBMDHAZ Z-score occurred as all groups decreased over 9 months (p < 0.03). Most tibia cortical bone outcomes increased over time (all p < 0.02), but changes did not differ across intervention groups. Whole eggs provide important nutritional benefits for children, but the bone responses to consumption of 8-10 eggs/wk over a period of 9 months in children entering the early stages of puberty were small. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The effects of 9 months of formulated whole-egg or milk powder food products as meal or snack replacements on executive function in preadolescents: A randomized, placebo-controlled trial.

BACKGROUND: Elevated brain choline is associated with better executive functions in preadolescents. Manipulating dietary choline prospectively in preadolescents using egg supplementation could improve executive functions via effects on brain cellular and neurotransmitter functions. OBJECTIVES: We tested the 9-month impacts of egg supplementation on executive functions. It was hypothesized that preadolescents who consumed meal or snack replacement products containing powder made from whole eggs would have the largest improvements in executive functions after 9 months compared to those consuming similar products with either added milk powder or gelatin as a placebo. METHODS: A randomized, parallel-group, double-blinded, placebo-controlled trial design was used. The executive functions of 122 preadolescents (58 females) aged 9-13 were analyzed before and after the 9-month intervention. The primary outcomes were 3 NIH Toolbox-Cognitive Battery measures of executive function: mental flexibility, working memory, and selective attention and inhibitory control. Participants were randomized to consume food products with either: 1) whole egg powder; 2) milk powder; or 3) gelatin as a placebo, all matched on macronutrient content and used as replacements for commonly consumed foods (i.e., waffles, pancakes, macaroni and cheese, ice cream, and brownies). Hypothesis testing used mixed-effects models that included physical activity and sleep scores as covariates. RESULTS: A statistically significant group × time interaction for selective attention and inhibitory control was found (P = 0.049) for the milk group. This interaction resulted from no change for the placebo group and an improvement in selective attention and inhibitory control performance for the milk group by a T-score of 5.8; the effect size (d) was 0.44 SD units. Other comparisons were statistically insignificant. CONCLUSIONS: Consumption of foods with added milk powder as a replacement for snacks or meals for 9 months improves selective attention and inhibitory control in preadolescents. Replacement of foods with added whole egg powder does not impact 9-month changes in preadolescent executive functions. This trial was registered at clinicaltrials.gov as NCT03739424.

Prevalence and trends of type 2 diabetes mellitus and prediabetes among community-dwelling heart failure patients in the United States.

AIMS: This study estimated national prevalence and trends of diagnosed and undiagnosed type 2 diabetes mellitus (T2DM) and prediabetes among heart failure (HF) patients in the U.S. METHODS: This cross-sectional study included 527 participants aged 20+ years with a diagnosis of HF, using data from the National Health and Nutrition Examination Survey 2005-2016. We assessed prevalence estimates of diagnosed and undiagnosed T2DM and prediabetes stratified by age-standardized sociodemographic and health characteristics. Trends of T2DM and prediabetes prevalence were examined using logistic regressions. RESULTS: Prevalence rates of diagnosed and undiagnosed T2DM among HF patients were 34.7% (95% confidence interval (CI), 29.2-40.3%) and 12.8% (95% CI, 9.2-16.9%), respectively. Prediabetes affected 39.1% (95% CI, 33.6-44.9%) of HF patients. Prevalence estimates of diagnosed T2DM were significantly different between non-Hispanic White (20.1% [95% CI, 13.5-27.6%]) and Hispanic participants (52.1% [95% CI, 35.9-68.0%]) (P < 0.001). The prevalence of T2DM and prediabetes did not significantly change between 2005 and 2016. CONCLUSIONS: Prevalence rates of T2DM and prediabetes among community-dwelling HF patients in the U.S. remained high between 2005 and 2016. Prevention of and targeted intervention for T2DM among at-risk HF patients is needed, particularly among those of Hispanic origin.

Dietary Patterns and Pediatric Bone.

PURPOSE OF REVIEW: Much of what we know about dietary patterns (DPs) and bone is derived from cross-sectional studies in adults. Given, establishing healthy bones during childhood serves as a blueprint for adult bone, it is important to better understand the role of DPs on pediatric bone. The purpose of this review is to determine if DPs influence bone strength in children. RECENT FINDINGS: The majority of studies investigating the role of DPs on pediatric bone are cross-sectional in design and examine data-derived "a posterori" DPs. Overall, the DPs characterized by high intakes of fruits and vegetables demonstrated positive effects on pediatric bone. Results from both "a posteriori" and "a priori" DPs approaches in children suggests that DPs dominated by the intake of fruits and vegetables might be beneficial for pediatric bone. Future studies may consider "a priori" DPs interventions to better understand relationship between DPs and pediatric bone.

Sex-Specific Muscular Mediation of the Relationship Between Physical Activity and Cortical Bone in Young Adults.

Muscle mass is a commonly cited mediator of the relationship between physical activity (PA) and bone, representing the mechanical forces generated during PA. However, neuromuscular properties (eg, peak force) also account for unique portions of variance in skeletal outcomes. We used serial multiple mediation to explore the intermediary role of muscle mass and force in the relationships between cortical bone and moderate-to-vigorous intensity PA (MVPA). In a cross-sectional sample of young adults (n = 147, 19.7 ± 0.7 years old, 52.4% female) cortical diaphyseal bone was assessed via peripheral quantitative computed tomography at the mid-tibia. Peak isokinetic torque in knee extension was assessed via Biodex dynamometer. Thigh fat-free soft tissue (FFST) mass, assessed via dual-energy X-ray absorptiometry, represented the muscular aspect of tibial mechanical forces. Habitual MVPA was assessed objectively over 7 days using Actigraph GT3X+ accelerometers. Participants exceeded MVPA guidelines (89.14 ± 27.29 min/day), with males performing 44.5% more vigorous-intensity activity relative to females (p < 0.05). Males had greater knee extension torque and thigh FFST mass compared to females (55.3%, and 34.2%, respectively, all p < 0.05). In combined-sex models, controlling for tibia length and age, MVPA was associated with strength strain index (pSSI) through two indirect pathways: (i) thigh FFST mass (b = 1.11 ± 0.37; 95% CI, 0.47 to 1.93), and (i) thigh FFST mass and knee extensor torque in sequence (b = 0.30 ± 0.16; 95% CI, 0.09 to 0.73). However, in sex-specific models MVPA was associated with pSSI indirectly through its relationship with knee extensor torque in males (b = 0.78 ± 0.48; 95% CI, 0.04 to 2.02) and thigh FFST mass in females (b = 1.12 ± 0.50; 95% CI, 0.37 to 2.46). Bootstrapped CIs confirmed these mediation pathways. The relationship between MVPA and cortical structure appears to be mediated by muscle in young adults, with potential sex-differences in the muscular pathway. If confirmed, these findings may highlight novel avenues for the promotion of bone strength in young adults. © 2019 American Society for Bone and Mineral Research.

Pentosidine Is Associated With Cortical Bone Geometry and Insulin Resistance in Otherwise Healthy Children.

Pentosidine is an advanced glycation end product (AGE) associated with fracture in adults with diabetes. AGE accumulation in bone collagen contributes to bone fragility but might also adversely influence bone turnover and, consequently, bone geometry. The relationships between AGEs and bone health have yet to be studied in children. Thus, the objective of this study was to assess relationships between pentosidine and cortical bone volumetric density, geometry, and estimated strength in children. Participants were otherwise healthy black and white boys and girls, ages 9 to 13 years, who were at sexual maturation stage 2 or 3 (N = 160). Tibia and radius cortical bone and muscle area (66% site) were assessed via pQCT. In fasting sera, insulin, glucose, and pentosidine were measured. The Quantitative Insulin Sensitivity Check Index (QUICKI), a measure of insulin sensitivity, was calculated. While controlling for race, sex, maturation, and height, pentosidine negatively correlated with QUICKI (P < 0.05). In unadjusted analyses, pentosidine was associated with lower radius and tibia cortical volumetric bone mineral density, bone mineral content (Ct.BMC), area (Ct.Ar), and thickness (Ct.Th); a larger radius endosteal circumference (Endo.Circ); and lower tibia polar strength strain index (all P < 0.05). While controlling for race, sex, maturation, height, and muscle area, pentosidine was negatively associated with tibia Ct.BMC, Ct.Ar, and Ct.Th but positively associated with Endo.Circ (all P < 0.05). Linear regression revealed a significant interaction between pentosidine and QUICKI in relation to tibia Ct.Th (pinteraction = 0.049), indicating that the negative relationship between pentosidine and Ct.Th was stronger in those with lower QUICKI (ie, greater insulin resistance). This is the first study to report evidence of a potentially adverse influence of AGEs on bone strength in otherwise healthy children. This relationship was strongest in children with the greatest insulin resistance, supporting further work in youth with chronic metabolic health conditions. © 2019 American Society for Bone and Mineral Research.

Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone Influence Muscle Outcomes in Children and Adolescents.

Increases in 25-hydroxyvitamin D concentrations are shown to improve strength in adults; however, data in pediatric populations are scant and equivocal. In this ancillary study of a larger-scale, multi-sited, double-blind, randomized, placebo-controlled vitamin D intervention in US children and adolescents, we examined the associations between changes in vitamin D metabolites and changes in muscle mass, strength, and composition after 12 weeks of vitamin D3 supplementation. Healthy male and female, black and white children and adolescents between the ages of 9 and 13 years from two US states (Georgia 34°N and Indiana 40°N) were enrolled in the study and randomly assigned to receive an oral vitamin D3 dose of 0, 400, 1000, 2000, or 4000 IU/d for 12 weeks between the winter months of 2009 to 2011 (N = 324). Analyses of covariance, partial correlations, and regression analyses of baseline and 12-week changes (post-baseline) in vitamin D metabolites (serum 25(OH)D, 1,25(OH)2 D, intact parathyroid hormone [iPTH]), and outcomes of muscle mass, strength, and composition (total body fat-free soft tissue [FFST], handgrip strength, forearm and calf muscle cross-sectional area [MCSA], muscle density, and intermuscular adipose tissue [IMAT]) were assessed. Serum 25(OH)D and 1,25(OH)2 D, but not iPTH, increased over time, as did fat mass, FFST, forearm and calf MCSA, forearm IMAT, and handgrip strength (p < 0.05). Vitamin D metabolites were not associated with muscle strength at baseline nor after the 12-week intervention. Changes in serum 25(OH)D correlated with decreases in forearm IMAT, whereas changes in serum iPTH predicted increases in forearm and calf MCSA and IMAT (p < 0.05). Overall, increases in 25(OH)D did not influence muscle mass or strength in vitamin D-sufficient children and adolescents; however, the role of iPTH on muscle composition in this population is unknown and warrants further investigation. © 2018 American Society for Bone and Mineral Research.

CD4+ and CD8+ T-Cell-Specific DNA Cytosine Methylation Differences Associated With Obesity.

OBJECTIVE: Lifestyle factors associated with obesity may alter epigenome-regulated gene expression. Most studies examining epigenetic changes in obesity have analyzed DNA 5´-methylcytosine (5mC) in whole blood, representing a weighted average of several distantly related and regulated leukocyte classes. To examine leukocyte-specific differences associated with obesity, a pilot study examining 5mC in three distinct leukocyte types isolated from peripheral blood of women with normal weight and obesity was conducted. METHODS: CD4+ T cells, CD8+ T cells, and CD16+ neutrophils were reiteratively isolated from blood, and 5mC levels were measured across >450,000 CG sites. RESULTS: Nineteen CG sites were differentially methylated between women with obesity and with normal weight in CD4+ cells, 16 CG sites in CD8+ cells, and 0 CG sites in CD16+ neutrophils (q < 0.05). There were no common differentially methylated sites between the T-cell types. The amount of visceral adipose tissue was strongly associated with the methylation level of 79 CG sites in CD4+ cells, including 4 CG sites in CLSTN1's promoter, which, this study shows, may regulate its expression. CONCLUSIONS: The methylomes of various leukocytes respond differently to obesity and levels of visceral adipose tissue. Highly significant differentially methylated sites in CD4+ and CD8+ cells in women with obesity that have apparent biological relevance to obesity were identified.

New Concepts in Vitamin D Requirements for Children and Adolescents: A Controversy Revisited.

North American and European authorities have identified thresholds up to 50 nmol/L serum 25-hydroxyvitamin D (25[OH]D) as optimal for pediatric vitamin D status. These recommendations are relative to skeletal endpoints, as vitamin D plays a pivotal role in bone mineral content (BMC) accretion. Suboptimal vitamin D consumption during youth may therefore hinder BMC acquisition, and contribute to an increased fracture risk. Though vitamin D requirements range between 400 and 800 IU/day, not all children achieve this. To encourage adequate vitamin D consumption, strategies such as supplementation, food labeling, and fortification, are currently being investigated. There is moderate support for the role of vitamin D supplementation on adolescent BMC accrual; however, factors such as age, maturation, population ancestry, and latitude, are not consistently accounted for across studies. Vitamin D is also linked with extraskeletal endpoints (e.g., muscle mass/function, adiposity, and metabolic health) in children, but the cross-sectional data do not necessarily align with results from experimental trials. Based on the evidence currently available, there is no need for a revision of the pediatric vitamin D recommendations at this time. Additional trials are required, however, to build upon the hypothesis-generating observational data, and to provide evidence for future vitamin D requirements across the globe.

Predicting Diaphyseal Cortical Bone Status Using Measures of Muscle Force Capacity.

PURPOSE: Muscle cross-sectional area (MCSA) is often used as a surrogate for the forces applied to bones during physical activity. Although MCSA is a strong predictor of cortical bone status, its use makes assumptions about the relationship between muscle size and force that are inaccurate. Furthermore, to measure MCSA and other muscle force surrogates typically requires expensive and/or radiative laboratory equipment. Thus, this study aimed to determine whether clinical laboratory- and field-based methodologies for measuring muscular force capacity accounted for similar variance in diaphyseal cortical bone status as a commonly used muscular force surrogate, MCSA, at the midtibia in young men and women. METHODS: Healthy young adults (n = 142, 19.7 ± 0.7 yr old, 52.8% female) were assessed via peripheral quantitative computed tomography at the midtibia for cortical bone status and MCSA. Muscle force capacity was measured via Biodex dynamometer, Nottingham leg extensor power rig, and Vertec vertical jump. Regression analysis compared the independent variance predicted by each muscle force measure with that of MCSA, accounting for relevant confounders. RESULTS: MCSA, knee extension peak torque, and peak anaerobic power from vertical jump were independent predictors of select cortical structural outcomes (cortical thickness and area, periosteal and endosteal circumference, and estimated strength) accounting for up to 78.4% of the variance explained (all P < 0.05). However, cortical volumetric bone mineral density was unrelated to any measure or surrogate of muscle force capacity. CONCLUSIONS: MCSA is a strong independent predictor of cortical bone structure; however, both laboratory- and field-based measures of peak torque and/or peak anaerobic power are promising alternatives, explaining similar and sometimes greater variance than MCSA.

A Twelve-Week Lifestyle Program to Improve Cardiometabolic, Behavioral, and Psychological Health in Hispanic Children and Adolescents.

OBJECTIVES: To examine the effectiveness of a 12-week lifestyle program on cardiometabolic, behavioral, and psychological outcomes among overweight Hispanic children and adolescents. DESIGN: A case series study with pre- and post-test analyses. Subjects/Settings/Location: A convenience sample of high-risk pediatric primary care patients (n = 22; 6 girls, 16 boys; M age = 11.73 ± 1.39 years) and their guardians in the Southeast United States. INTERVENTION: Twice per week 60 min (total of 24 h) of moderate-to-vigorous intensity boxing exercise training, 12 h of nutrition education for guardians, and a 30-min pediatrician appointment. OUTCOME MEASURES: Cardiometabolic (height [m], weight [kg], waist circumference [cm], body-mass index [BMI], BMI-z, BMI%, cholesterol [mg/dL], triglycerides [mg/dL], glucose [mg/dL], and low-density lipoprotein and high-density lipoprotein cholesterol [mg/dL]), behavioral (objective free time physical activity [PA] and sedentary time [min/day]), and psychological (self-determined exercise motivation) outcomes were measured/calculated, and paired-samples t-tests were conducted. RESULTS: A significant reduction was observed in waist circumference t(17) = -2.57, p = 0.020, d = 0.64; BMI% t(15) = -2.53, p = 0.023, d = 0.20; fasting glucose t(15) = -6.43, p < 0.001, d = 1.67; and amotivation (-) t(17) = -2.29, p = 0.036, d = 0.64; whereas a significant increase was identified in moderate t(10) = 4.01, p = 0.002, d = 1.23 and vigorous t(10) = 3.41, p = 0.007, d = 1.07 intensity PA; intrinsic motivation t(17) = 2.71, p = 0.015, d = 0.38; and introjected regulation t(17) = 2.74, p = 0.014, d = 0.64. CONCLUSIONS: A 12-week lifestyle program can be effective in improving selected health markers among overweight Hispanic children and adolescents. The positive changes in fasting glucose, BMI, and waist suggest that the participants are currently at lower risk for both type 2 diabetes and cardiovascular disease as a result of the Confidence, Ownership, Responsibility, and Exercise program.

Obese Versus Normal-Weight Late-Adolescent Females have Inferior Trabecular Bone Microarchitecture: A Pilot Case-Control Study.

Though still a topic of debate, the position that skeletal health is compromised with obesity has received support in the pediatric and adult literature. The limited data relating specifically to trabecular bone microarchitecture, however, have been relatively inconsistent. The aim of this pilot cross-sectional case-control study was to compare trabecular bone microarchitecture between obese (OB) and normal-weight (NW) late-adolescent females. A secondary aim was to compare diaphyseal cortical bone outcomes between these two groups. Twenty-four non-Hispanic white females, ages 18-19 years, were recruited into OB (n = 12) or NW (n = 12) groups based on pre-specified criteria for percent body fat (≥32 vs. <30, respectively), body mass index (>90th vs. 20th-79th, respectively), and waist circumference (≥90th vs. 25th-75th, respectively). Participants were also individually matched on age, height, and oral contraceptive use. Using magnetic resonance imaging, trabecular bone microarchitecture was assessed at the distal radius and proximal tibia metaphysis, and cortical bone architecture was assessed at the mid-radius and mid-tibia diaphysis. OB versus NW had lower apparent trabecular thickness (radius and tibia), higher apparent trabecular separation (radius), and lower apparent bone volume to total volume (radius; all P < 0.050). Some differences in radius and tibia trabecular bone microarchitecture were retained after adjusting for insulin resistance or age at menarche. Mid-radius and mid-tibia cortical bone volume and estimated strength were lower in the OB compared to NW after adjusting for fat-free soft tissue mass (all P < 0.050). These trabecular and cortical bone deficits might contribute to the increased fracture risk in obese youth.

Distinctions in gene-specific changes in DNA methylation in response to folic acid supplementation between women with normal weight and obesity.

BACKGROUND/OBJECTIVES: Obesity and maternal folate deficiency are associated with increased risk for neural tube defects (NTDs). Limited knowledge exists on the impact of folate status or obesity on DNA methylation of genes related to NTD risk and folate metabolism. SUBJECTS/METHODS: Women (18-35y) with normal weight (NW; BMI 18.5-24.9kg/m2; n=12) and obesity (OB; BMI >30kg/m2; n=6) were provided FA (800µg/d) for 8-weeks. Serum folate concentration and changes in DNA methylation across 2098 CpG sites in 91 genes related to NTD risk and folate metabolism were examined. RESULTS: Serum folate concentration increased in both groups following FA supplementation, but OB maintained a relative lower concentration (NW; 38.36±2.50-71.41±3.02nmol/L and OB; 27.12±3.09-56.85±3.90nmol/L). Methylation of 56 and 99 CpG sites changed in response to supplementation in NW and OB, respectively, and majority of these sites decreased in methylation in both groups. Only 4 CpG sites responded to supplementation in both groups. Gene ontology analysis revealed a response to supplementation in 61 biological processes (BPs) from the selected genes. Five of the 61 BPs were identified only in NW, including neural tube closure, while 13 of the 61 BPs were enriched only in OB, including folate metabolism, vitamin B12 metabolism and methylation related processes. CONCLUSIONS: Changes in DNA methylation in genes related to NTD risk and folate metabolism in response to FA supplementation were different in NW and OB. Increased NTD risk and abnormal folate metabolism in obesity may be due to a distinctive epigenetic response to folate status in these genes.

Zinc Supplementation Does Not Alter Indicators of Insulin Secretion and Sensitivity in Black and White Female Adolescents.

Background: Zinc is a micronutrient involved in the production of, and peripheral sensitivity to, pancreatic ß cell-derived insulin. To our knowledge, the effect of zinc supplementation on insulin outcomes, and potential risk of diabetes, in otherwise healthy children in the United States has not been investigated.Objective: The objective of this study was to determine the influence of zinc supplementation on insulin outcomes in black and white girls in the early stages of adolescence. A secondary objective was to determine relations between baseline zinc concentrations and insulin outcomes.Methods: Healthy black and white girls aged 9-11 y were randomly assigned to daily supplementation of zinc (9 mg elemental Zn/d; n = 75; blacks: n = 35) or placebo (n = 72; blacks: n = 32) for 4 wk. Fasting serum insulin, glucose, and C-peptide were assessed at baseline and at 4 wk. C-peptide and glucose values were used to calculate the computer model-derived homeostatic model assessment of insulin resistance (HOMA2-IR). Changes in outcome measures were compared by using repeated-measures, mixed-model ANOVA.Results: Baseline plasma zinc was not correlated with C-peptide (r = -0.07), insulin (r = -0.06), or HOMA2-IR (r = -0.09) (all P > 0.05) after controlling for race and age. Treatment × time interactions for C-peptide and HOMA2-IR were not significant (both P > 0.05). Although the treatment × race × time interactions for C-peptide and HOMA2-IR were not significant (both P = 0.08), black girls who received the placebo experienced slight increases in C-peptide (15.7%) and HOMA2-IR (17.7%) (P = 0.06).Conclusions: Four weeks of zinc supplementation had no effect on insulin outcomes in healthy black and white early-adolescent girls, although C-peptide and HOMA2-IR tended to increase in black girls who received placebo. Additional trials that are appropriately powered should further explore the effect of zinc on markers of diabetes risk, and whether race affects this relation. This trial was registered at clinicaltrials.gov as NCT01892098.

Associations among osteocalcin, leptin and metabolic health in children ages 9-13 years in the United States.

BACKGROUND: This study aimed to investigate the relationships among osteocalcin, leptin and metabolic health outcomes in children ages 9-13 years. METHODS: This was a cross-sectional analysis of baseline data from 161 boys and 157 girls (ages 9-13 years) who previously participated in a double-blinded randomized placebo controlled trial of vitamin D supplementation. Relationships among fasting serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), leptin, and metabolic health outcomes were analyzed. RESULTS: Approximately 52% of study participants were obese based on percent body fat cutoffs (>25% for boys and >32% for girls) and about 5% had fasting serum glucose within the prediabetic range (i.e. 100 to 125 mg/dL). Serum tOC was not correlated with leptin, glucose, insulin, HOMA-IR, or HOMA-ß after adjusting for percent body fat. However, serum ucOC negatively correlated with leptin (partial r = -0.16; p = 0.04) and glucose (partial r = -0.16; p = 0.04) after adjustment for percent body fat. Leptin was a positive predictor of insulin, glucose, HOMA-IR, and HOMA-ß after adjusting for age, sex and percent body fat (all p < 0.001). CONCLUSIONS: These data depict an inverse relationship between leptin and various metabolic health outcomes in children. However, the notion that tOC or ucOC link fat with energy metabolism in healthy children was not supported. CLINICAL TRIAL REGISTRATION NUMBER: NCT00931580.

Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years.

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (ßIndirect Effect = 0.321, p < 0.001). However, this relationship was moderated in the children with high (ßIndirect Effect = 0.200, p < 0.001) versus normal (ßIndirect Effect = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research.

DNA Methylation Changes in Whole Blood and CD16+ Neutrophils in Response to Chronic Folic Acid Supplementation in Women of Childbearing Age.

Folate, a water-soluble vitamin, is a key source of one-carbon groups for DNA methylation, but studies of the DNA methylation response to supplemental folic acid yield inconsistent results. These studies are commonly conducted using whole blood, which contains a mixed population of white blood cells that have been shown to confound results. The objective of this study was to determine if CD16+ neutrophils may provide more specific data than whole blood for identifying DNA methylation response to chronic folic acid supplementation. The study was performed in normal weight (BMI 18.5 - 24.9 kg/m2) women (18 - 35 y; n = 12), with blood samples taken before and after 8 weeks of folic acid supplementation at 800 µg/day. DNA methylation patterns from whole blood and isolated CD16+ neutrophils were measured across >485,000 CpG sites throughout the genome using the Infinium HumanMethylation450 BeadChip. Over the course of the 8-week supplementation, 6746 and 7513 CpG sites changed (p < 0.05) in whole blood and CD16+ neutrophils, respectively. DNA methylation decreased in 68.4% (whole blood) and 71.8% (CD16+ neutrophils) of these sites. There were only 182 CpG sites that changed in both the whole blood and CD16+ neutrophils, 139 of which changed in the same direction. These results suggest that the genome-wide DNA methylation response to chronic folic acid supplementation is different between whole blood and CD16+ neutrophils and that a single white blood cell type may function as a more specific epigenetic reporter of folate status than whole blood.

Vitamin D Supplementation Does Not Impact Insulin Resistance in Black and White Children.

CONTEXT: Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings. OBJECTIVE: The objective of this study was to determine the dose-response of vitamin D supplementation on fasting glucose, insulin, and a surrogate measure of insulin resistance in white and black children aged 9­13 years, who participated in the Georgia, Purdue, and Indiana University (or GAPI) trial: a 12-week multisite, randomized, triple-masked, dose-response, placebo-controlled vitamin D trial. DESIGN: Black and white children in the early stages of puberty (N = 323, 50% male, 51% black) were equally randomized to receive vitamin D3 (0, 400, 1000, 2000, or 4000 IU/day) for 12 weeks. Fasting serum 25-hydroxyvitamin D (25(OH)D), glucose and insulin were assessed at baseline and weeks 6 and 12. Homeostasis model assessment of insulin resistance was used as a surrogate measure of insulin resistance. Statistical analyses were conducted as intent-to-treat using a mixed effects model. RESULTS: Baseline serum 25(OH)D was inversely associated with insulin (r = −0.140, P = 0.017) and homeostasis model assessment of insulin resistance (r = −0.146, P = 0.012) after adjusting for race, sex, age, pubertal maturation, fat mass, and body mass index. Glucose, insulin, and insulin resistance increased (F > 5.79, P < .003) over the 12 weeks, despite vitamin D dose-dependent increases in serum 25(OH)D. CONCLUSIONS: Despite significant baseline inverse relationships between serum 25(OH)D and measures of insulin resistance, vitamin D supplementation had no impact on fasting glucose, insulin, or a surrogate measure of insulin resistance over 12 weeks in apparently healthy children.

The Effects of Preexercise Caffeinated Coffee Ingestion on Endurance Performance: An Evidence-Based Review.

Endurance athletes commonly ingest caffeine as a means to enhance training intensity and competitive performance. A widely-used source of caffeine is coffee, however conflicting evidence exists regarding the efficacy of coffee in improving endurance performance. In this context, the aims of this evidence-based review were threefold: 1) to evaluate the effects of preexercise coffee on endurance performance, 2) to evaluate the effects of coffee on perceived exertion during endurance performance, and 3) to translate the research into usable information for athletes to make an informed decision regarding the intake of caffeine via coffee as a potential ergogenic aid. Searches of three major databases were performed using terms caffeine and coffee, or coffee-caffeine, and endurance, or aerobic. Included studies (n = 9) evaluated the effects of caffeinated coffee on human subjects, provided the caffeine dose administered, administered caffeine ≥ 45 min before testing, and included a measure of endurance performance (e.g., time trial). Significant improvements in endurance performance were observed in five of nine studies, which were on average 24.2% over controls for time to exhaustion trials, and 3.1% for time to completion trials. Three of six studies found that coffee reduced perceived exertion during performance measures significantly more than control conditions (p < .05). Based on the reviewed studies there is moderate evidence supporting the use of coffee as an ergogenic aid to improve performance in endurance cycling and running. Coffee providing 3-8.1 mg/kg (1.36-3.68 mg/lb) of caffeine may be used as a safe alternative to anhydrous caffeine to improve endurance performance.

Zinc Supplementation Increases Procollagen Type 1 Amino-Terminal Propeptide in Premenarcheal Girls: A Randomized Controlled Trial.

BACKGROUND: Data have shown that healthy children and adolescents have an inadequate intake of zinc, an essential nutrient for growth. It is unclear whether zinc supplementation can enhance bone health during this rapid period of growth and development. OBJECTIVE: The primary aim of this study was to determine the effect of zinc supplementation on biochemical markers of bone turnover and growth in girls entering the early stages of puberty. The secondary aim was to test moderation by race, body mass index (BMI) classification, and plasma zinc status at baseline. METHODS: One hundred forty seven girls aged 9-11 y (46% black) were randomly assigned to a daily oral zinc tablet (9 mg elemental zinc; n = 75) or an identical placebo (n = 72) for 4 wk. Fasting plasma zinc, procollagen type 1 amino-terminal propeptide (P1NP; a bone formation marker), carboxy-terminal telopeptide region of type 1 collagen (ICTP; a bone resorption marker), and insulin-like growth factor I (IGF-I) were assessed at baseline and post-test. Additional markers of bone formation (osteocalcin) and resorption (urinary pyridinoline and deoxypyridinoline) were also measured. RESULTS: Four weeks of zinc supplementation increased plasma zinc concentrations compared with placebo [mean change, 1.8 µmol/L (95% CI: 1.0, 2.6) compared with 0.2 µmol/L (95% CI: -0.3, 0.7); P < 0.01]. Zinc supplementation also increased serum P1NP concentrations compared with placebo [mean change, 23.8 µmol/L (95% CI: -14.9, 62.5) compared with -31.0 µmol/L (95% CI: -66.4, 4.2); P = 0.04). There was no effect from zinc supplementation on osteocalcin, ICTP, pyridinoline, deoxypyridinoline, or IGF-I. There was no moderation by race, BMI classification, or plasma zinc status at baseline. CONCLUSIONS: Our data suggest that 4 wk of zinc supplementation increases bone formation in premenarcheal girls. Further studies are needed to determine whether supplemental zinc can improve childhood bone strength. This trial was registered at clinicaltrials.gov as NCT01892098.