First name
Babette
Middle name
S
Last name
Zemel

Title

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

Year of Publication

2022

Number of Pages

1069-1077

Date Published

08/2022

ISSN Number

2191-0251

Abstract

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, SpO; apnea hypopnea index, AHI; arousal index, AI; maximum end-tidal CO; 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 SpO 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, SpO nadir, and inflammation. The independent association of visceral adiposity with insulin resistance highlights the potential role of VAT in obesity-related chronic disease.

DOI

10.1515/jpem-2021-0745

Alternate Title

J Pediatr Endocrinol Metab

PMID

35822712

Title

Marked skeletal muscle deficits are associated with 6-minute walk distance in paediatric pulmonary hypertension.

Year of Publication

2021

Number of Pages

1426-1433

Date Published

2021 Sep

ISSN Number

1467-1107

Abstract

<p><strong>BACKGROUND: </strong>Poor growth is common in children with pulmonary hypertension; however, skeletal muscle deficits have not been described and the association between muscle deficits and functional status is unknown.</p>

<p><strong>METHODS: </strong>Patients aged 8-18 years with pulmonary hypertension (diagnostic Groups 1, 2, or 3) and World Health Organization functional class I or II underwent dual-energy absorptiometry to measure leg lean mass Z-score (a surrogate for skeletal muscle). Muscle strength was assessed using dynamometry. Physical activity questionnaires were administered. Clinical data, including 6-minute walk distance, were reviewed. Relationships between skeletal muscle, physical activity score, and 6-minute walk distance were assessed by correlations and linear regression.</p>

<p><strong>RESULTS: </strong>Sixteen patients (12.1 ± 3.2 years, 50% female, 56% Group 1, 56% functional class II) were enrolled. Leg lean mass Z-score was significantly less than reference data (-1.40 ± 1.12 versus 0.0 ± 0.9, p &lt; 0.001) and worse in those with functional class II versus I (-2.10 ± 0.83 versus -0.50 ± 0.73, p &lt; 0.01). Leg lean mass Z-score was positively associated with right ventricular systolic function by tricuspid annular plane systolic Z-score (r = 0.54, p = 0.03) and negatively associated with indexed pulmonary vascular resistance (r = -0.78, p &lt; 0.001). Leg lean mass Z-score and forearm strength were positively associated with physical activity score. When physical activity score was held constant, leg lean mass Z-score independently predicted 6-minute walk distance (R2 = 0.39, p = 0.03).</p>

<p><strong>CONCLUSIONS: </strong>Youth with pulmonary hypertension demonstrate marked skeletal muscle deficits in association with exercise intolerance. Future studies should investigate whether low leg lean mass is a marker of disease severity or an independent target that can be improved.</p>

DOI

10.1017/S1047951121000342

Alternate Title

Cardiol Young

PMID

33568240

Title

Deficits in the Functional Muscle-Bone Unit in Youths with Fontan Physiology.

Year of Publication

2021

Number of Pages

202-207

Date Published

2021 11

ISSN Number

1097-6833

Abstract

<p><strong>OBJECTIVE: </strong>To determine whether dual energy X-ray absorptiometry (DXA), a clinically available tool, mirrors the magnitude of deficits in trabecular and cortical bone mineral density (BMD) demonstrated on peripheral quantitative computed tomography in youth with Fontan physiology.</p>

<p><strong>STUDY DESIGN: </strong>We aimed to describe DXA-derived BMD at multiple sites and to investigate the relationship between BMD and leg lean mass, a surrogate for skeletal muscle loading. Subjects with Fontan (n&nbsp;=&nbsp;46; aged 5-20&nbsp;years) underwent DXA in a cross-sectional study of growth and bone and muscle health as described previously. Data from the Bone Mineral Density in Childhood Study were used to calculate age-, sex-, and race-specific BMD z-scores of the whole body, lumbar spine, hip, femoral neck, distal one-third radius, ultradistal radius, and leg lean mass z-score (LLMZ).</p>

<p><strong>RESULTS: </strong>Fontan BMD z-scores were significantly lower than reference at all sites-whole body, -0.34&nbsp;±&nbsp;0.85 (P&nbsp;=&nbsp;.01); spine, -0.41&nbsp;±&nbsp;0.96 (P&nbsp;=&nbsp;.008); hip, -0.75&nbsp;±&nbsp;1.1 (P&nbsp;&lt;&nbsp;.001); femoral neck, -0.73&nbsp;±&nbsp;1.0 (P&nbsp;&lt;&nbsp;.001); distal one-third radius, -0.87&nbsp;±&nbsp;1.1 (P&nbsp;&lt;&nbsp;.001); and ultradistal radius. -0.92&nbsp;±&nbsp;1.03 (P&nbsp;&lt;&nbsp;.001)-as was LLMZ (-0.93&nbsp;±&nbsp;1.1; P&nbsp;&lt;&nbsp;.001). Lower LLMZ was associated with lower BMD of the whole body (R&nbsp;=&nbsp;0.40; P&nbsp;&lt;&nbsp;.001), lumbar spine (R&nbsp;=&nbsp;0.16; P&nbsp;=&nbsp;.005), total hip (R&nbsp;=&nbsp;0.32; P&nbsp;&lt;&nbsp;.001), femoral neck (R&nbsp;=&nbsp;0.47; P&nbsp;&lt;&nbsp;.001), and ultradistal radius (R&nbsp;=&nbsp;0.35; P&nbsp;&lt;&nbsp;.001).</p>

<p><strong>CONCLUSIONS: </strong>Patients with Fontan have marked deficits in both cortical (hip, distal one-third radius) and trabecular (lumbar spine, femoral neck, ultradistal radius) BMD. Lower LLMZ is associated with lower BMD and may reflect inadequate skeletal muscle loading. Interventions to increase muscle mass may improve bone accrual.</p>

DOI

10.1016/j.jpeds.2021.06.068

Alternate Title

J Pediatr

PMID

34214589

Title

Deficits in bone density and structure in children and young adults following Fontan palliation.

Year of Publication

2015

Number of Pages

12-6

Date Published

2015 Aug

ISSN Number

1873-2763

Abstract

<p><strong>BACKGROUND: </strong>Survival of patients with congenital heart disease has improved such that there are now more adults than children living with these conditions. Complex single ventricle congenital heart disease requiring Fontan palliation is associated with multiple risk factors for impaired bone accrual. Bone density and structure have not been characterized in these patients.</p>

<p><strong>METHODS: </strong>Tibia peripheral quantitative computed tomography (pQCT) was used to assess trabecular and cortical volumetric bone mineral density (vBMD), cortical dimensions, and calf muscle area in 43 Fontan participants (5-33 years old), a median of 10 years following Fontan palliation. pQCT outcomes were converted to sex- and race-specific Z-scores relative to age based on &gt;700 healthy reference participants. Cortical dimensions and muscle area were further adjusted for tibia length.</p>

<p><strong>RESULTS: </strong>Height Z-scores were lower in Fontan compared to reference participants (mean ± SD: -0.29 ± 1.00 vs. 0.25 ± 0.93, p &lt; 0.001); BMI Z-scores were similar (0.16 ± 0.88 vs. 0.35 ± 1.02, p = 0.1). Fontan participants had lower trabecular vBMD Z-scores (-0.85 ± 0.96 vs. 0.01 ± 1.02, p &lt; 0.001); cortical vBMD Z-scores were similar (-0.17 ± 0.98 vs. 0.00 ± 1.00, p = 0.27). Cortical dimensions were reduced with lower cortical area (-0.59 ± 0.84 vs. 0.00 ± 0.88, p&lt;0.001) and periosteal circumference (-0.50 ± 0.82 vs. 0.00 ± 0.84, p &lt; 0.001) Z-scores, compared to reference participants. Calf muscle area Z-scores were lower in the Fontan participants (-0.45 ± 0.98 vs. 0.00 ± 0.96, p = 0.003) and lower calf muscle area Z-scores were associated with smaller periosteal circumference Z-scores (R = 0.62, p &lt; 0.001). Musculoskeletal deficits were not associated with age, Fontan characteristics, parathyroid hormone or vitamin D levels.</p>

<p><strong>CONCLUSIONS: </strong>Children and young adults demonstrate low trabecular vBMD, cortical structure and muscle area following Fontan. Muscle deficits were associated with smaller periosteal dimensions. Future studies should determine the fracture implications of these deficits and identify interventions to promote musculoskeletal development.</p>

DOI

10.1016/j.bone.2015.04.012

Alternate Title

Bone

PMID

25882907

Title

Lean mass deficits, vitamin D status and exercise capacity in children and young adults after Fontan palliation.

Year of Publication

2014

Number of Pages

1702-7

Date Published

2014 Nov

ISSN Number

1468-201X

Abstract

<p><strong>OBJECTIVE: </strong>We sought to evaluate body composition in children and young adults with Fontan physiology. Leg lean mass (LM) deficits correlate with diminished exercise capacity in other populations and may contribute to exercise limitations in this cohort.</p>

<p><strong>METHODS: </strong>This cross-sectional study included whole body dual energy X-ray absorptiometry scans in 50 Fontan participants ≥5 years, and measures of peak oxygen consumption (VO2) in 28. Whole body and leg LM (a measure of skeletal muscle) were converted to sex- and race-specific Z-scores, relative to age and stature, based on 992 healthy reference participants.</p>

<p><strong>RESULTS: </strong>Median age was 11.5 (range 5.1-33.5) years at 9.3 (1.1-26.7) years from Fontan. Height Z-scores were lower in Fontan compared with reference participants (-0.47±1.08 vs 0.25±0.93, p&lt;0.0001). Body mass index Z-scores were similar (0.15±0.98 vs 0.35±1.02, p=0.18). LM Z-scores were lower in Fontan compared with reference participants (whole body LM -0.33±0.77 vs 0.00±0.74, p=0.003; leg LM -0.89±0.91 vs 0.00±0.89, p&lt;0.0001). LM Z-scores were not associated with age or Fontan characteristics. Leg LM Z-scores were lower in vitamin D deficient versus sufficient Fontan participants (-1.47±0.63 vs -0.71±0.92, p=0.01). Median per cent predicted peak VO2 was 81% (range 13%-113%) and was associated with leg LM Z-scores (r=0.54, p=0.003).</p>

<p><strong>CONCLUSIONS: </strong>Following Fontan, children and young adults are shorter than their peers and have significant LM deficits. Skeletal muscle deficits were associated with vitamin D deficiency and reduced exercise capacity. Future studies should examine the progression of these deficits to further understand the contribution of peripheral musculature to Fontan exercise capacity.</p>

DOI

10.1136/heartjnl-2014-305723

Alternate Title

Heart

PMID

24973081

Title

Sex differences in childhood sleep and health implications.

Year of Publication

2021

Number of Pages

474-484

Date Published

2021 Sep

ISSN Number

1464-5033

Abstract

<p><strong>CONTEXT: </strong>Sleep is critical for optimal childhood metabolic health and neurodevelopment. However, there is limited knowledge regarding childhood sex differences in sleep, including children with neurodevelopmental disorders, and the impact of such differences on metabolic health.</p>

<p><strong>OBJECTIVE: </strong>To evaluate if sex differences in childhood sleep exist and if sleep associates with metabolic health outcomes equally by sex. Using autism spectrum disorder (ASD) as a case study, we also examine sleep sex differences in children with a neurodevelopmental disorder.</p>

<p><strong>METHODS: </strong>A narrative review explored the literature focussing on sex differences in childhood sleep.</p>

<p><strong>RESULTS: </strong>Sex differences in sleep were not detected among pre-adolescents. However, female adolescents were more likely to report impaired sleep than males. Childhood obesity is more common in males. Shorter sleep duration may be associated with obesity in male pre-adolescents/adolescents; although findings are mixed. ASD is male-predominant; yet, there was an indication that pre-adolescent female children with ASD had more impaired sleep.</p>

<p><strong>CONCLUSION: </strong>Sex differences in sleep appear to emerge in adolescence with more impaired sleep in females. This trend was also observed among pre-adolescent female children with ASD. Further research is needed on sex differences in childhood sleep and metabolic health and the underlying mechanisms driving these differences.</p>

DOI

10.1080/03014460.2021.1998624

Alternate Title

Ann Hum Biol

PMID

35105205

Title

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

Year of Publication

2022

Date Published

2022 Jan 25

ISSN Number

1523-4681

Abstract

<p>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), ages 5 to 30 years (52% female). At baseline and follow up, alloHSCT survivors demonstrated lower height-, weight-, 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&lt;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 less than -2.0, respectively, at baseline and follow up. 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. This article is protected by copyright. All rights reserved.</p>

DOI

10.1002/jbmr.4513

Alternate Title

J Bone Miner Res

PMID

35080067

Title

Sarcopenic Obesity in Rheumatoid Arthritis: Prevalence and Impact on Physical Functioning.

Year of Publication

2021

Date Published

2021 Sep 24

ISSN Number

1462-0332

Abstract

<p><strong>OBJECTIVE: </strong>We determined the prevalence of sarcopenic obesity in patients with rheumatoid arthritis (RA) using multiple methods and assessed associations with physical functioning.</p>

<p><strong>METHODS: </strong>This study evaluated data from three RA cohorts. Whole-body dual-energy absorptiometry (DXA) measures of appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI) were converted to age, sex, and race-specific Z-Scores and categorized using a recently validated method and compared it to a widely-used existing method. The prevalence of body composition abnormalities in RA was compared with two reference populations. In the RA cohorts, associations between body composition and change in the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB) in follow-up were assessed using linear and logistic regression, adjusting for age, sex, race, and study.</p>

<p><strong>RESULTS: </strong>The prevalence of low lean mass and sarcopenic obesity were higher in patients with RA (14.2; 12.6%, respectively) compared with the reference population cohorts (7-10%; 4-4.5%, respectively, all p&lt; 0.05). There was only moderate agreement among methods of sarcopenic obesity categorization (Kappa 0.45). The recently validated method categorized fewer subjects as obese, and many of these were categorized as low lean mass only. Low lean mass, obesity, and sarcopenic obesity were each associated with higher HAQ and lower SPPB at baseline and numerically greater worsening.</p>

<p><strong>CONCLUSION: </strong>RA patients had higher rates of low lean mass and sarcopenic obesity than the general population. The recently validated methods characterized body composition changes differently from traditional methods and were more strongly associated with physical function.</p>

DOI

10.1093/rheumatology/keab710

Alternate Title

Rheumatology (Oxford)

PMID

34559201

Title

Adipocytokines and Associations with Abnormal Body Composition in Rheumatoid Arthritis.

Year of Publication

2021

Date Published

2021 Sep 24

ISSN Number

2151-4658

Abstract

<p><strong>PURPOSE: </strong>We determined associations between adipokines and abnormal body composition in patients with rheumatoid arthritis (RA).</p>

<p><strong>METHODS: </strong>Combining data from three RA cohorts, whole-body dual-energy absorptiometry measures of appendicular lean mass and fat mass indices were converted to age, sex, and race-specific Z-Scores. Lean mass relative to fat mass was determined based on prior methods. Independent associations between body composition profiles and circulating levels of adiponectin, leptin, and fibroblast growth factor(FGF)-21 were assessed using linear and logistic regression models adjusting for demographics and study cohort. We also determined the improvement in the area-under-the-curve (AUC) for prediction of low lean mass when adipokines were added to predictive models that included clinical factors such as demographics, study, and body mass index (BMI).</p>

<p><strong>RESULTS: </strong>Among 419 participants, older age was associated with higher levels of all adipokines while higher C-reactive protein was associated with lower adiponectin levels and higher FGF-21 levels. Greater fat mass was strongly associated with lower adiponectin levels and higher leptin and FGF-21 levels. Higher levels of adiponectin, leptin, and FGF-21 were independently associated with low lean mass. The addition of adiponectin and leptin levels to regression models improved prediction of low lean mass when combined with demographics, study, and BMI (AUC 0.75 v. 0.66).</p>

<p><strong>CONCLUSIONS: </strong>Adipokines are associated with both excess adiposity and low lean mass in patients with RA. Improvements in the prediction of body composition abnormalities suggest that laboratory screening could help identify patients with altered body composition who may be at greater risk of adverse outcomes.</p>

DOI

10.1002/acr.24790

Alternate Title

Arthritis Care Res (Hoboken)

PMID

34558809

Title

Sarcopenia and preserved bone mineral density in paediatric survivors of high-risk neuroblastoma with growth failure.

Year of Publication

2021

Date Published

2021 Jun 29

ISSN Number

2190-6009

Abstract

<p><strong>BACKGROUND: </strong>Survival from paediatric high-risk neuroblastoma (HR-NBL) has increased, but cis-retinoic acid (cis-RA), the cornerstone of HR-NBL therapy, can cause osteoporosis and premature physeal closure and is a potential threat to skeletal structure in HR-NBL survivors. Sarcopenia is associated with increased morbidity in survivors of paediatric malignancies. Low muscle mass may be associated with poor prognosis in HR-NBL patients but has not been studied in these survivors. The study objective was to assess bone density, body composition and muscle strength in HR-NBL survivors compared with controls.</p>

<p><strong>METHODS: </strong>This prospective cross-sectional study assessed areal bone mineral density (aBMD) of the whole body, lumbar spine, total hip, femoral neck, distal 1/3 and ultradistal radius and body composition (muscle and fat mass) using dual-energy X-ray absorptiometry (DXA) and lower leg muscle strength using a dynamometer. Measures expressed as sex-specific standard deviation scores (Z-scores) included aBMD (adjusted for height Z-score), bone mineral apparent density (BMAD), leg lean mass (adjusted for leg length), whole-body fat mass index (FMI) and ankle dorsiflexion peak torque adjusted for leg length (strength-Z). Muscle-specific force was assessed as strength relative to leg lean mass. Outcomes were compared between HR-NBL survivors and controls using Student's t-test or Mann-Whitney U test. Linear regression models examined correlations between DXA and dynamometer outcomes.</p>

<p><strong>RESULTS: </strong>We enrolled 20 survivors of HR-NBL treated with cis-RA [13 male; mean age: 12.4&nbsp;±&nbsp;1.6&nbsp;years; median (range) age at therapy initiation: 2.6 (0.3-9.1) years] and 20 age-, sex- and race-matched controls. Height-Z was significantly lower in HR-NBL survivors compared with controls (-1.73&nbsp;±&nbsp;1.38 vs. 0.34&nbsp;±&nbsp;1.12, P&nbsp;&lt;&nbsp;0.001). Areal BMD-Z, BMAD-Z, FMI-Z, visceral adipose tissue and subcutaneous adipose tissue were not significantly different in HR-NBL survivors compared with controls. Compared with controls, HR-NBL survivors had lower leg lean mass-Z (-1.46&nbsp;±&nbsp;1.35 vs. -&nbsp;0.17&nbsp;±&nbsp;0.84, P&nbsp;&lt;&nbsp;0.001) and strength-Z (-1.13&nbsp;±&nbsp;0.86 vs. -&nbsp;0.15&nbsp;±&nbsp;0.71, P&nbsp;&lt;&nbsp;0.001). Muscle-specific force was lower in HR-NBL survivors compared with controls (P&nbsp;&lt;&nbsp;0.05).</p>

<p><strong>CONCLUSIONS: </strong>Bone mineral density and adiposity are not severely impacted in HR-NBL survivors with growth failure, but significant sarcopenia persists years after treatment. Future studies are needed to determine if sarcopenia improves with muscle-specific interventions in this population of cancer survivors.</p>

DOI

10.1002/jcsm.12734

Alternate Title

J Cachexia Sarcopenia Muscle

PMID

34184837

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