Mechanisms of obesity in Prader–Willi syndrome

Khan, Muhammad Aurangzeb; Gerasimidis, Konstantinos; Edwards, Christine; Shaikh, M Guftar

doi:10.1111/ijpo.12177

Cited by 72 publications

(47 citation statements)

References 61 publications

(102 reference statements)

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“…In addition to increased appetite and decreased satiety (6), the propensity for obesity is exacerbated by decreased physical activity, altered body composition and a reduced metabolic rate (7). Obesity is associated with a number of complications, such as cardiovascular disease, diabetes mellitus, hypertension, sleep disturbances (including sleep apnea), poor quality of life, and increased mortality in PWS (8)(9)(10). Despite improvements in early diagnosis of PWS, all-cause mortality of those with PWS remains signi cantly increased compared to the general population (11,12).…”

Section: Introductionmentioning

confidence: 99%

Variability and Change Over Time of Weight and BMI Among Adolescents and Adults with Prader-Willi Syndrome: A 6-month text-based observational study

Vrana-Diaz

Balasubramanian²,

Kayadjanian

et al. 2020

Preprint

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Abstract Background: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder in which hyperphagia (excessive appetite) is a hallmark feature. Understanding how weight changes over time in this population is important for capturing the contemporary natural history of the disorder as well as assessing the impact of new treatments for hyperphagia. Therefore, we aimed to determine the feasibility of a remote assessment of weight change over time in PWS. Methods: We developed a text message-based, prospective cohort study of adolescents and adults with PWS to assess changes in weight and body mass index (BMI) over a six-month period. Weight was collected weekly, while changes in height, living situation, access to food, activity level, and medication were collected at three-month intervals. Results: One hundred and sixty-five participants enrolled in the study, with a mean age of 19.7 years (range 12 - 48). There was considerable variability in weight across participants (range: 76.8 – 207.7 kg). Thirty-three percent of the participants were normal weight, while 15% were overweight and 52% were obese. Overall, the weight of the study participants increased over the study period (mean weight change +2.35%), while BMI was relatively stable, albeit high (mean BMI of 31.4 at baseline, mean BMI percent change + 1.42%). Changes in living situation, activity, food access, and medication had limited impact on weight and BMI changes. Multivariable analysis found that time, sex, age, and percentage of life on growth hormone (GH) therapy were statistically significant fixed effects. Participants submitted more than 95% of possible weight data points across the 26 weeks of the study. Conclusions: This remote, observational study of weight change in PWS showed small increases in weight and BMI over a six-month period. Participants were highly compliant with this text message-based study, suggesting that mobile technology-based data collection was manageable for the participants. We anticipate that the results of this study will inform clinical trials for hyperphagia/obesity related therapies in PWS and provide a basis for understanding the efficacy of new therapies for hyperphagia in the real-world setting.

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Section: Introductionmentioning

confidence: 99%

Variability and Change Over Time of Weight and BMI Among Adolescents and Adults with Prader-Willi Syndrome: A 6-month text-based observational study

Vrana-Diaz

Balasubramanian²,

Kayadjanian

et al. 2020

Preprint

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“…Overall, survival in PWS is especially threatened by obesity, which is secondary to hyperphagia from a disturbance in the hypothalamic pathways of satiety control, irregularity in hormones that regulate food intake, and reduced energy expenditure in view of poor feeding and hypotonia [14,15]. Obesity is the most common cause of metabolic complications and can reduce the quality of life.…”

Section: Discussionmentioning

confidence: 99%

Age Distribution, Comorbidities and Risk Factors for Thrombosis in Prader–Willi Syndrome

Butler

Oyetunji

Manzardo

2020

Genes

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Prader–Willi syndrome (PWS) is an imprinting disorder caused by lack of expression of the paternally inherited 15q11.2–q13 chromosome region. The risk of death from obesity-related complications can worsen with age, but survival trends are improving. Comorbidities and their complications such as thrombosis or blood clots and venous thromboembolism (VTE) are uncommon but reported in PWS. Two phases of analyses were conducted in our study: unadjusted and adjusted frequency with odds ratios and a regression analysis of risk factors. Individuals with PWS or non-PWS controls with exogenous obesity were identified by specific International Classification of Diseases (ICD)-9 diagnostic codes reported on more than one occasion to confirm the diagnosis of PWS or exogenous obesity in available national health claims insurance datasets. The overall average age or average age per age interval (0–17 year, 18–64 year, and 65 year+) and gender distribution in each population were similar in 3136 patients with PWS and 3945 non-PWS controls for comparison purposes, with exogenous obesity identified from two insurance health claims dataset sources (i.e., commercial and Medicare advantage or Medicaid). For example, 65.1% of the 3136 patients with PWS were less than 18 years old (subadults), 33.2% were 18–64 years old (adults), and 1.7% were 65 years or older. After adjusting for comorbidities that were identified with diagnostic codes, we found that commercially insured PWS individuals across all age cohorts were 2.55 times more likely to experience pulmonary embolism (PE) or deep vein thrombosis (DVT) than for obese controls (p-value: 0.013; confidence interval (CI): 1.22–5.32). Medicaid-insured individuals across all age cohorts with PWS were 0.85 times more likely to experience PE or DVT than obese controls (p-value: 0.60; CI: 0.46–1.56), with no indicated age difference. Age and gender were statistically significant predictors of VTEs, and they were independent of insurance coverage. There was an increase in occurrence of thrombotic events across all age cohorts within the PWS patient population when compared with their obese counterparts, regardless of insurance type.

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“…However, children with PWS receiving GH treatment show less inflammation compared with those who are GH naïve . These findings suggest that the control, regulation and function of the metabolic and immune systems may potentially differ between the obesity associated with PWS and NSO .…”

Section: Introductionmentioning

confidence: 94%

“…Insufficient physical activity is not just a problem in the general child population, with only 42% of children ages 6–11 years meeting current guidelines , but more so in children with PWS with only 8% meeting such guidelines . Active Play @ Home was a unique home‐based, parent‐led, physical activity intervention designed for families with a child who had PWS because of unique behavioural, psychological and physical challenges of this syndrome . The Active Play @ Home curriculum was designed based on current physical activity guidelines to stimulate activity participation and improve motor proficiency .…”

Section: Introductionmentioning

confidence: 99%

Changes in cardiometabolic markers in children with Prader–Willi syndrome and nonsyndromic obesity following participation in a home‐based physical activity intervention

et al. 2018

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Summary Background Physical activity is associated with improved cardiometabolic markers in children with nonsyndromic obesity (NSO). Prader–Willi Syndrome (PWS) is a neurodevelopmental disorder characterized by obesity. Objective To compare cardiometabolic changes in response to a home‐based parent‐facilitated physical activity intervention between children with PWS or with NSO. Methods Participants included 18 children with PWS (age = 10.5 ± 0.7y; body fat = 44.6 ± 2.0%) and 30 children with NSO (age = 9.7 ± 0.2y; body fat = 44.8 ± 1.2%). Active Play @ Home was a 24‐week physical activity intervention curriculum containing playground‐based and active video games completed 4 days per week. Pre‐ and post‐intervention measurements included physical activity, body composition, blood samples analysed for glucose, insulin, lipids and cytokines, and insulin resistance computed using the homeostatic model of assessment for insulin resistance (HOMA‐IR). Results All children (n = 48) showed a significant decrease in Interleukin‐8 (3.64 ± 0.24 vs. 3.06 ± 0.22 pg/mL). Children with obesity who did not gain or who lost body fat percentage (n = 18) demonstrated a significant decrease in HOMA‐IR (3.17 ± 0.39 vs. 2.72 ± 0.34) and an increase in high‐density lipoprotein (44.30 ± 2.51 vs. 47.29 ± 2.59 mg/dL). All other measurements showed no significant changes. Conclusions The most favourable changes in cardiometabolic factors were observed in children with nonsyndromic obesity who demonstrated no gain or a decrease in body fat percentage.

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Mechanisms of obesity in Prader–Willi syndrome

Abstract: Summary 23Obesity is the most common cause of metabolic complications and poor quality of life in

Cited by 72 publications

References 61 publications

Variability and Change Over Time of Weight and BMI Among Adolescents and Adults with Prader-Willi Syndrome: A 6-month text-based observational study

Variability and Change Over Time of Weight and BMI Among Adolescents and Adults with Prader-Willi Syndrome: A 6-month text-based observational study

Age Distribution, Comorbidities and Risk Factors for Thrombosis in Prader–Willi Syndrome

Changes in cardiometabolic markers in children with Prader–Willi syndrome and nonsyndromic obesity following participation in a home‐based physical activity intervention

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