Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with low levels of insulin resistance among heart failure patients.

BACKGROUND AND AIMS: Heart failure (HF) patients are at risk of developing type 2 diabetes. This study examined the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and insulin resistance among U.S. adults with HF. METHODS AND RESULTS: Using data from National Health and Nutrition Examination Survey 1999-2016 cycles, we included 348 individuals aged 20+ years with HF and no history of diabetes. DASH diet adherence index quartile 1 indicated the lowest and quartile 4 indicated the highest adherence. The highest level of insulin resistance was defined by the upper tertile of the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Associations between level of insulin resistance and DASH diet adherence and its linear trends were examined using logistic regressions. Trend analyses showed that participants in upper DASH diet adherence index quartiles were more likely older, female, non-Hispanic White, of normal weight, and had lower levels of fasting insulin than those in lower quartiles. Median values of HOMA-IR from lowest to highest DASH diet adherence index quartiles were 3.1 (interquartile range, 1.8-5.5), 2.9 (1.7-5.6), 2.1 (1.1-3.7), and 2.1 (1.3-3.5). Multivariable logistic analyses indicated that participants with the highest compared to the lowest DASH adherence showed 77.1% lower odds of having the highest level of insulin resistance (0.229, 95% confidence interval: 0.073-0.716; p = 0.017 for linear trend). CONCLUSION: Good adherence to the DASH diet was associated with lower insulin resistance among community-dwelling HF patients. Heart healthy dietary patterns likely protect HF patients from developing type 2 diabetes.

Glycemic Control and Bone in Diabetes.

PURPOSE OF REVIEW: This review summarizes recent developments on the effects of glycemic control and diabetes on bone health. We discuss the foundational cellular mechanisms through which diabetes and impaired glucose control impact bone biology, and how these processes contribute to bone fragility in diabetes. RECENT FINDINGS: Glucose is important for osteoblast differentiation and energy consumption of mature osteoblasts. The role of insulin is less clear, but insulin receptor deletion in mouse osteoblasts reduces bone formation. Epidemiologically, type 1 (T1D) and type 2 diabetes (T2D) associate with increased fracture risk, which is greater among people with T1D. Accumulation of cortical bone micro-pores, micro-vascular complications, and AGEs likely contribute to diabetes-related bone fragility. The effects of youth-onset T2D on peak bone mass attainment and subsequent skeletal fragility are of particular concern. Further research is needed to understand the effects of hyperglycemia on skeletal health through the lifecycle, including the related factors of inflammation and microvascular damage.

Celiac Disease and Bone Health in Children and Adolescents: A Systematic Review and Meta-Analysis.

CONTEXT: Celiac disease is characterized by deficits in bone mineral accrual and longitudinal growth. OBJECTIVE: The purpose of this study was to determine the differences in bone health and stature among children and adolescents with celiac disease versus healthy controls. DATA SOURCES: Articles published before February 27, 2018 were located using searches of the Physical Education Index (n = 186), PubMed (n = 180), Scopus (n = 3), SPORTDiscus (n = 3), and Web of Science (n = 4). STUDY SELECTION: Bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed via dual-energy X-ray absorptiometry, and height was measured using a stadiometer. DATA EXTRACTION: Effect sizes (ES) were calculated as follows: the mean difference of the celiac disease group and healthy control group, divided by the pooled standard deviation. The inverse variance weight was used to calculate the overall mean ES. Random-effects models were used to aggregate a mean ES, 95% confidence intervals (CIs) and to identify potential moderators. RESULTS: The results of 30 effects gathered from 12 studies published between 1996 and 2017 indicated BMC (ES = -0.54, 95% CI: -0.69 to -0.40; p < 0.0001) and aBMD (ES = 0.72, 95% CI: -0.96 to -0.47; p < 0.0001) were lower in youth with celiac disease. LIMITATIONS: These results were limited to only cross-sectional and baseline data from longitudinal studies reporting BMC and BMD, however did not assess changes in bone health over time. CONCLUSION: Children and adolescents with celiac disease have suboptimal bone health and shorter stature.

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.

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.

Load-specific physical activity scores are related to tibia bone architecture.

Assessment of physical activity in clinical bone studies is essential. Two bone-specific physical activity scoring methods, the Bone Loading History Questionnaire (BLHQ) and Bone-Specific Physical Activity Questionnaire (BPAQ), have shown correlations with bone density and geometry, but not architecture. The purpose of this study was to determine relationships between physical activity scoring methods and bone architecture in non-Hispanic white adolescent females (N = 24; 18-19 years of age). Bone loading scores (BLHQ [hip and spine] and past BPAQ) and energy expenditure (7-day physical activity recall) were determined from respective questionnaires. Estimates of trabecular and cortical bone architecture at the nondominant radius and tibia were assessed via magnetic resonance imaging. Total body and regional areal bone mineral density (aBMD), as well as total body fat mass and fat-free soft tissue (FFST) mass were assessed via dual energy X-ray absorptiometry. Pearson's correlations and partial correlations adjusting for height, total body fat mass, and FFST were performed. Hip BLHQ scores were correlated with midtibia cortical volume (r = .43; p = .03). Adjusted hip and spine BLHQ scores were correlated with all midtibia cortical measures (r = .50-0.58; p < .05) and distal radius apparent trabecular number (r = .46-0.53; p < .05). BPAQ scores were correlated with all midtibia cortical (r = .41-0.51; p < .05) and most aBMD (r = .47-0.53; p < .05) measures. Energy expenditure was inversely associated with femoral neck aBMD only after statistical adjustment (r = .49, p < .05). These data show that greater load-specific physical activity scores, but not energy expenditure, are indicative of greater midtibia cortical bone quality, thus supporting the utility of these instruments in musculoskeletal research.

Nutritional practices associated with low energy availability in Division I female soccer players.

The purpose of this study was to examine macronutrient intake, energy density and energy intake distribution that may be associated with low energy availability (EA) in Division I female soccer players. The energy intake, exercise energy expenditure and EA of 19 participants (18-21 years) was assessed during the pre-, mid- and postseasons. Repeated measures analysis of variance was performed to examine the changes across the season. Chi-square analysis was performed to examine the distribution of participants meeting the American College of Sports Medicine recommendations for carbohydrate and protein consumption. Independent t-tests were used to compare differences between groups. The proportion of athletes who did not meet the American College of Sports Medicine recommendations for carbohydrate intake (6-10 g . kg(-1) BW) was significantly greater in the low (<30 kcal . kg(-1) LBM) than higher (≥ 30 kcal . kg(-1) LBM) EA group (χ(2) (1) = 7.5; P = 0.006). Participants with low compared to higher EA consumed a lower energy dense dinner (0.8 ± 0.1 vs. 1.4 ± 0.1 kcal . g(-1); P = 0.004) after a soccer match during midseason. No differences in the percentage (%) of kilocalories from food (84.5 ± 2.0% vs. 84.7 ± 2.6%), sports drinks (7.3 ± 1.4% vs. 6.0 ± 3.2%), other drinks (7.6 ± 1.5 % vs. 6.0 ± 1.5%) or bars/gels/beans (1.7 ± 0.6 vs. 3.0 ± 1.5) were observed in participants with low compared to higher EA (P > 0.05) during the pre- and midseasons. Identifying inadequate carbohydrate intake and the practice of consuming lower energy dense meals may be important in preventing low EA conditions and consequently the Female Athlete Triad.

Bone mass accrual in children.

PURPOSE OF REVIEW: Bone accrual during childhood and adolescence is critical for the attainment of peak bone mass and is a major contributing factor towards osteoporosis in later life. Bone mass accrual is influenced by nonmodifiable factors, such as genetics, sex, race, ethnicity, and puberty, as well as modifiable factors, such as physical activity and diet. Recent progress in bone imaging has allowed clinicians and researchers to better measure the morphology, density, and strength of the growing skeleton, thereby encompassing key characteristics of peak bone strength. In this review, the patterning of bone accrual and contributors to these changes will be described, as well as new techniques assessing bone mass and strength in pediatric research and clinical settings. RECENT FINDINGS: This review discusses factors influencing peak bone mass attainment and techniques used to assess the human skeleton. SUMMARY: The rate of bone accrual and the magnitude of peak bone mass attainment occurs in specific patterns varying by sex, race, ethnicity, longitudinal growth, and body composition. Physical activity, diet, and nutritional status impact these processes. There is a need for longitudinal studies utilizing novel imaging modalities to unveil factors involved in the attainment and maintenance of peak bone strength.

The relationship between food selectivity and stature in pediatric patients with avoidant-restrictive food intake disorder - an electronic medical record review.

BACKGROUND: We aimed to characterize stature in pediatric patients with avoidant/restrictive food intake disorder (ARFID), including associations between body size and nutrient intake and height. METHODS: We conducted a secondary analysis of pre-treatment data from 60 patients diagnosed with ARFID that were collected from the electronic medical record. Anthropometric measurements were converted to age- and sex-specific Z-scores using pediatric CDC growth charts. Spearman correlations were performed to test the relationship between height and weight/BMI Z-scores as well as height Z-score and diet variables. RESULTS: On average, height (-0.35 ± 1.38), weight (-0.58 ± 1.56), and BMI (-0.56 ± 1.48) Z-scores tended to be lower than what would be expected in a generally healthy pediatric population. Percent of individuals with height, weight, or BMI Z-score < -2.0 was 8%, 20%, and 17%, respectively. BMI (P < 0.05) and weight (P < 0.05) were positively associated with height Z-score. Further, intake of some nutrients (e.g., calcium, vitamin D) correlated positively with height Z-score (all P < 0.05). CONCLUSIONS: The cross-sectional relationships reported in this study suggest that in children with ARFID, body weight and consumption of bone-augmenting nutrients such as calcium and vitamin D correlated with height. A thorough understanding of the clinical manifestations of malnutrition and longitudinal effects of restrictive eating in patients with ARFID is critical.

We examined data on growth and height for a sample of 60 children with highly selective eating consistent with an eating/feeding disorder termed avoidant/restrictive food intake disorder (ARFID). These children received treatment in an intensive multidisciplinary intervention program. We found that children had significantly lower weight and body mass index (BMI) compared to same sex and age peers, with a trend toward lower height. Greater body size and intake of specific nutrients was related to taller stature in this sample. Children with ARFID may be at greater risk of impaired growth secondary to highly restricted food intake, a health outcome which should be studied to inform screening and intervention practices.

Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes.

BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern.

Cardiometabolic Risk and Its Relationship With Visceral Adiposity in Children With Cerebral Palsy.

Context: Adults with cerebral palsy (CP) display a higher prevalence of cardiometabolic disease compared with the general population. Studies examining cardiometabolic disease risk in children with CP are limited. Objective: The purpose of this study was to determine if children with CP exhibit higher cardiometabolic risk than typically developing children, and to examine its relationship with visceral adiposity and physical activity. Methods: Thirty ambulatory children with CP and 30 age-, sex-, and race-matched typically developing control children were tested for blood lipids, glucose, and the homeostatic model assessment of insulin resistance (HOMA-IR). Visceral fat was assessed using dual-energy x-ray absorptiometry. Physical activity was assessed using accelerometer-based monitors. Results: Children with CP had higher total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol (non-HDL-C), glucose, prevalence of dyslipidemia, prevalence of prediabetes, and visceral fat mass index (VFMI) and lower physical activity than controls (all P < .05). In the groups combined, non-HDL-C and glucose were positively related to VFMI (r = 0.337 and 0.313, respectively, P < .05), and non-HDL-C and HOMA-IR were negatively related to physical activity (r = -0.411 and -0.368, respectively, P < .05). HOMA-IR was positively related to VFMI in children with CP (r = 0.698, P < .05), but not in controls. Glucose was not related to physical activity in children with CP, but it was negatively related in controls (r = -0.454, P < .05). Conclusion: Children with CP demonstrate early signs of cardiometabolic disease, which are more closely related to increased visceral adiposity than decreased physical activity.

Bone resorption and incretin hormones following glucose ingestion in healthy emerging adults.

Background: Studies in adults indicate that macronutrient ingestion yields an acute anti-resorptive effect on bone, reflected by decreases in C-terminal telopeptide (CTX), a biomarker of bone resorption, and that gut-derived incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), facilitate this response. There remain knowledge gaps relating to other biomarkers of bone turnover, and whether gut-bone cross-talk is operative during the years surrounding peak bone strength attainment. This study first, describes changes in bone resorption during oral glucose tolerance testing (OGTT), and second, tests relationships between changes in incretins and bone biomarkers during OGTT and bone micro-structure. Methods: We conducted a cross-sectional study in 10 healthy emerging adults ages 18-25 years. During a multi-sample 2-hour 75 g OGTT, glucose, insulin, GIP, GLP-1, CTX, bone-specific alkaline phosphatase (BSAP), osteocalcin, osteoprotegerin (OPG), receptor activator of nuclear factor kappa-ß ligand (RANKL), sclerostin, and parathyroid hormone (PTH) were assayed at mins 0, 30, 60, and 120. Incremental areas under the curve (iAUC) were computed from mins 0-30 and mins 0-120. Tibia bone micro-structure was assessed using second generation high resolution peripheral quantitative computed tomography. Results: During OGTT, glucose, insulin, GIP, and GLP-1 increased significantly. CTX at min 30, 60, and 120 was significantly lower than min 0, with a maximum decrease of about 53 % by min 120. Glucose-iAUC0-30 inversely correlated with CTX-iAUC0-120 (rho = -0.91, P < 0.001), and GLP-1-iAUC0-30 positively correlated with BSAP-iAUC0-120 (rho = 0.83, P = 0.005), RANKL-iAUC0-120 (rho = 0.86, P = 0.007), and cortical volumetric bone mineral density (rho = 0.93, P < 0.001). Conclusions: Glucose ingestion yields an anti-resorptive effect on bone metabolism during the years surrounding peak bone strength. Cross-talk between the gut and bone during this pivotal life stage requires further attention.

Bone health in avoidant/restrictive food intake disorder: a narrative review.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) is an eating/feeding disturbance characterized by severe food avoidance or restriction that results in faltering growth, nutritional deficiencies, dependence on formula supplementation, and/or significant psychosocial impairment. Compared to other eating disorders, ARFID is observed to have an earlier childhood onset and chronic course without intervention. Childhood represents a sensitive period for longitudinal growth and bone accrual, setting the stage for long-term health outcomes associated with longevity and quality of life, including risk for fracture and osteoporosis. RESULTS: This narrative review discusses published scientific literature on bone health in individuals with ARFID by describing the current understanding of ARFID's effect on bone health, how common dietary constraints characteristic of ARFID may present unique risks to bone health, and the current clinical recommendations for bone health assessment. Reviewing what is known of clinical data from anorexia nervosa (AN) and similar cohorts, the chronicity and etiology of dietary restriction observed in ARFID are hypothesized to compromise bone health significantly. Although limited, examination of bone health in ARFID patients suggests children with ARFID tend to have shorter stature compared to healthy reference datasets and have lower bone density compared to healthy individuals, similar to those with AN. There remains a substantial knowledge gap in how ARFID may interrupt bone accrual during childhood and adolescence, and subsequent impact on attainment of peak bone mass and peak bone strength. The longitudinal effects of ARFID may be subtle and overlooked clinically in the absence of severe weight loss or growth stunting. Early identification and remediation of threats to bone mass accrual have significant personal and population-level implications. CONCLUSION: For patients with ARFID, delayed identification and intervention to address feeding disturbances may have a long-lasting impact on various body systems and processes, including those relating to longitudinal growth and bone mass accrual. Further research employing rigorous prospective observational and/or randomized study designs are required to clearly define effects of ARFID, as well as clinical interventions aimed at addressing ARFID-related feeding disturbances, on bone accrual.

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).

Insulin resistance and skeletal health.

PURPOSE OF REVIEW: Bone fragility is a complication of type 2 diabetes (T2D), and insulin resistance is suspected to contribute to diabetes-related bone deficits. This article provides an overview of emerging clinical research involving insulin resistance and bone health by summarizing recent publications, identifying existing knowledge gaps, and suggesting 'next steps' for this evolving field of research. RECENT FINDINGS: Clinical studies in children and adults report greater bone density in people with increased insulin resistance, but these associations are often attenuated when adjusting for body size. Advancements in bone imaging methods allow for assessment of nuanced characteristics of bone quality and strength that extend beyond standard bone mineral density assessment methods. For example, several recent studies focusing on lumbar spine trabecular bone score, a relatively new measure of trabecular bone quality from dual-energy X-ray absorptiometry, have reported generally consistent inverse associations with insulin resistance. Longitudinal studies using advanced imaging methods capable of evaluating trabecular bone microstructure and strength, such as high-resolution peripheral quantitative computed tomography, are lacking. Studies in younger individuals are sparse, but emerging data suggest that peak bone mass attainment might be threatened by diabetes progression, and increased visceral fat, suppressed muscle-bone unit, advanced glycation end-products, sedentary lifestyle, and poor diet quality might contribute to diabetes effects on bone. Prospective studies during the transition from adolescence to young adulthood are required. SUMMARY: Insulin resistance is a main feature of T2D, which is suspected to contribute to subclinical diabetes-related threats to bone health. Future clinical studies should focus on the critical years surrounding peak bone mass and peak bone strength attainment using contemporary imaging techniques.

Visceral fat and arterial stiffness in youth with healthy weight, obesity, and type 2 diabetes.

BACKGROUND AND OBJECTIVES: Visceral fat is associated with increased cardiovascular risk in adults, but studies in youth are limited. We assessed associations between visceral fat and arterial stiffness in youth with healthy weight, obesity and type 2 diabetes and determined whether relationships were independent of clinical estimates of body fatness. METHODS: This cross-sectional sample included youth ages 10-23 years (67% female, 56% non-black) with healthy weight (body mass index [BMI] = 5th-85th percentile, n = 236), obesity (BMI ≥ 95th percentile, n = 224) and type 2 diabetes (BMI ≥ 95th percentile, n = 145). Visceral fat was assessed via dual-energy X-ray absorptiometry. Carotid-femoral pulse wave velocity (PWV) was assessed via applanation tonometry. Obesity and type 2 diabetes groups were combined for final analyses. Analyses accounted for age, sex, ancestry and mean arterial pressure. RESULTS: Visceral fat and PWV were greater in youth with obesity versus healthy weight (p < 0.001). In youth with obesity, but not healthy weight, visceral fat was positively associated with PWV (p < 0.001) and was predictive of PWV beyond BMI and waist circumference. CONCLUSIONS: Visceral fat likely contributes to subclinical cardiovascular complications in youth. Since cardiovascular health tracks from adolescence to adulthood, longitudinal studies in youth with obesity are required to define the role of visceral fat in lifelong cardiovascular disease risk.

Bone metabolism and incretin hormones following glucose ingestion in young adults with pancreatic insufficient cystic fibrosis.

Background: Gut-derived incretin hormones, including glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1), regulate post-prandial glucose metabolism by promoting insulin production. GIP, GLP-1, and insulin contribute to the acute bone anti-resorptive effect of macronutrient ingestion by modifying bone turnover. Cystic fibrosis (CF) is associated with exocrine pancreatic insufficiency (PI), which perturbs the incretin response. Cross-talk between the gut and bone ("gut-bone axis") has not yet been studied in PI-CF. The objectives of this study were to assess changes in biomarkers of bone metabolism during oral glucose tolerance testing (OGTT) and to test associations between incretins and biomarkers of bone metabolism in individuals with PI-CF. Methods: We performed a secondary analysis of previously acquired blood specimens from multi-sample OGTT from individuals with PI-CF ages 14-30 years (n = 23). Changes in insulin, incretins, and biomarkers of bone resorption (C-terminal telopeptide of type 1 collagen [CTX]) and formation (procollagen type I N-terminal propeptide [P1NP]) during OGTT were computed. Results: CTX decreased by 32% by min 120 of OGTT (P < 0.001), but P1NP was unchanged. Increases in GIP from 0 to 30 mins (rho = -0.48, P = 0.03) and decreases in GIP from 30 to 120 mins (rho = 0.62, P = 0.002) correlated with decreases in CTX from mins 0-120. Changes in GLP-1 and insulin were not correlated with changes in CTX, and changes in incretins and insulin were not correlated with changes in P1NP. Conclusions: Intact GIP response was correlated with the bone anti-resorptive effect of glucose ingestion, represented by a decrease in CTX. Since incretin hormones might contribute to development of diabetes and bone disease in CF, the "gut-bone axis" warrants further attention in CF during the years surrounding peak bone mass attainment.

Visceral adipose tissue and cardiometabolic risk factors in young Hispanic and non-Hispanic girls.

Background: Risk factors for cardiometabolic diseases (e.g., type 2 diabetes, cardiovascular disease) can begin developing in childhood. Elevated body mass index (BMI) is associated with greater likelihood of developing such diseases; however, this relationship varies by race and ethnicity. Notably, Hispanics tend to have high rates of obesity and are disproportionately affected by type 2 diabetes. We aimed to determine if visceral adiposes tissue (VAT) is associated with cardiometabolic risk factors (i.e., triglycerides, cholesterol, insulin resistance, C-reactive protein, and blood pressure), independent of BMI percentile, in a sample of primarily Hispanic adolescent girls. Methods and results: A total of 337 girls (73% Hispanic) took part in the cross-sectional study. Hispanic girls generally had greater BMI percentile, VAT, and cardiometabolic risk factors compared to non-Hispanic girls. Multiple linear regression was used to assess the relationships between Dual-energy X-ray Absorptiometry (DXA)-derived VAT and cardiometabolic outcomes, controlling for BMI percentile (<85th percentile or ≥85th percentile), age, ethnicity (Hispanic/non-Hispanic), and Tanner stage. Significant interactions between VAT and BMI percentile were identified for almost all cardiometabolic outcomes. Upon stratification, the association between VAT and cardiometabolic outcomes was strongest in girls ≥85th BMI percentile, as compared to girls <85th percentile. However, VAT was only significantly associated with higher triglycerides (girls ≥85th percentile) and higher insulin resistance (both BMI percentiles) after stratification. Conclusion: VAT was associated with increased triglycerides and insulin resistance in girls with overweight or obesity. These findings warrant further investigation between VAT and cardiometabolic health in Hispanic adolescents who tend to accumulate more adipose tissue during adolescence.

Persistent Musculoskeletal Deficits in Pediatric, Adolescent and Young Adult Survivors of Allogeneic Hematopoietic Stem-Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a common therapy for pediatric hematologic malignancies. With improved supportive care, addressing treatment-related late effects is at the forefront of survivor long-term health and quality of life. We previously demonstrated that alloHSCT survivors had increased adiposity, decreased lean mass, and lower bone density and strength, 7 years (median) from alloHSCT compared to their healthy peers. Yet it is unknown whether these deficits persist. Our longitudinal study characterized changes in muscle and bone over a period of 3.4 (range, 2.0 to 4.9) years in 47 childhood alloHSCT survivors, age 5-26 years at baseline (34% female). Tibia cortical bone geometry and volumetric density and lower leg muscle cross-sectional area (MCSA) were assessed via peripheral quantitative computed tomography (pQCT). Anthropometric and pQCT measurements were converted to age, sex, and ancestry-specific standard deviation scores, adjusted for leg length. Muscle-specific force was assessed as strength relative to MCSA adjusted for leg length (strength Z-score). Measurements were compared to a healthy reference cohort (n = 921), age 5-30 years (52% female). At baseline and follow-up, alloHSCT survivors demonstrated lower height Z-scores, weight Z-scores, and leg length Z-scores compared to the healthy reference cohort. Deficits in MCSA, trabecular volumetric bone density, and cortical bone size and estimated strength (section modulus) were evident in survivors (all p < 0.05). Between the two study time points, anthropometric, muscle, and bone Z-scores did not change significantly in alloHSCT survivors. Approximately 15% and 17% of alloHSCT survivors had MCSA and section modulus Z-score < -2.0, at baseline and follow-up, respectively. Furthermore, those with a history of total body irradiation compared to those without demonstrated lower MCSA at follow-up. The persistent muscle and bone deficits in pediatric alloHSCT survivors support the need for strategies to improve bone and muscle health in this at-risk population. © 2022 American Society for Bone and Mineral Research (ASBMR).

Visceral adiposity is related to insulin sensitivity and inflammation in adolescents with obesity and mild sleep disordered breathing.

OBJECTIVES: To evaluate the relationships between adipose tissue distribution, insulin secretion and sensitivity, sleep-disordered breathing, and inflammation in obese adolescents. METHODS: Cross-sectional study of 56 obese adolescents who underwent anthropometric measures, dual-energy X-ray absorptiometry, overnight polysomnography, oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test. Correlation and regression analyses were used to assess relationships between adiposity, insulin secretion and sensitivity, measures of sleep-disordered breathing (oxyhemoglobin nadir, SpO2; apnea hypopnea index, AHI; arousal index, AI; maximum end-tidal CO2; non-REM sleep duration), and inflammation (high-sensitivity C-reactive protein, hsCRP). RESULTS: Subjects (55% female) were mean (SD) 14.4 (2.1) years, with BMI Z-score of 2.3 (0.4). AHI was >5 in 10 (18%) subjects and 1< AHI ≤5 in 22 (39%). Visceral adipose tissue area (VAT) was positively correlated with OGTT 1 and 2 h insulin and 1 h glucose, and hsCRP (r=0.3-0.5, p≤0.007 for each). VAT was negatively correlated with sensitivity to insulin (r=-0.4, p=0.005) and SpO2 nadir (r=-0.3, p=0.04) but not with other sleep measures. After adjustment for BMI-Z, sex, population ancestry, age, and sleep measures, VAT remained independently associated with insulin measures and 1 h glucose, but no other measures of glycemia. SAT was not associated with measures of glycemia or insulin resistance. CONCLUSIONS: Among adolescents with obesity, visceral adiposity was associated with insulin resistance, SpO2 nadir, and inflammation. The independent association of visceral adiposity with insulin resistance highlights the potential role of VAT in obesity-related chronic disease.