Untargeted metabolomics identifies a plasma sphingolipid-related signature associated with lifestyle intervention in prepubertal children with obesity.

OBJECTIVE: Childhood obesity is a strong risk factor for adult obesity and metabolic diseases, including type 2 diabetes and cardiovascular disease. Early lifestyle intervention in children with obesity reduces future disease risk. The objective of this study is to identify metabolic signatures associated with lifestyle intervention in prepubertal children with obesity. METHODS: Thirty-five prepubertal children (7-10 years) with obesity (body mass index (BMI)>2 standard deviations) were enrolled in the study and participated in a 6-month-long lifestyle intervention program. Physiological and biochemical data and blood samples were collected both at baseline and after the intervention. A liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach was applied to obtain a comprehensive profiling of plasma samples, identifying 2581 distinct metabolite. Principal component analysis (PCA) was performed to consolidate all features into 8 principal components. Associations between metabolites and physiological and biochemical variables were investigated. RESULTS: The intervention program significantly decreased mean (95% CI) BMI standard deviation score from 3.56 (3.29-3.84) to 3.11 (2.88-3.34) (P<0.001). PCA identified one component (PC1) significantly altered by the intervention (Bonferroni adjusted P=0.008). A sphingolipid metabolism-related signature was identified as the major contributor to PC1. Sphingolipid metabolites were decreased by the intervention, and included multiple sphingomyelin, ceramide, glycosylsphingosine and sulfatide species. Changes in several sphingolipid metabolites were associated with intervention-induced improvements in HbA1c levels. CONCLUSIONS: Decreased circulating sphingolipid-related metabolites were associated with lifestyle intervention in prepubertal children with obesity, and correlated to improvements in HbA1c.

Health-related quality of life of X-linked hypophosphatemia in Spain.

BACKGROUND: Health-related quality of life (HRQoL) of patients with X-linked hypophosphatemia (XLH) is lower than that of both the general population and the patients with other chronic diseases, mainly due to diagnostic delay, treatment difficulties, poor psychosocial support, and problems with social integration. Early diagnosis and optimal treatment are paramount to control the disease in patients with XLH, avoid complications, and maintain or improve their HRQoL. We, therefore, analyzed the HRQoL of pediatric and adult patients with XLH treated with conventional therapy in Spain. RESULTS: We used several versions of the EuroQol-5 dimensions (EQ-5D) instrument according to the age of patients with XLH. Then we compared the HRQoL of patients to that of the general Spanish population. Children with XLH (n = 21) had moderate problems in walking about (61.9%), washing or dressing themselves (9.52%), and performing their usual activities (33.33%). They also felt moderate pain or discomfort (61.9%) and were moderately anxious or depressed (23.81%). Adults with XLH (n = 29) had lower HRQoL, with problems in walking (93%, with 3.45% unable to walk independently), some level of pain (86%, with 3.45% experiencing extreme pain), problems with their usual activities (80%) and self-care (> 50%), and reported symptoms of anxiety and/or depression (65%). There were important differences with the general Spanish population. CONCLUSIONS: XLH impacts negatively on physical functioning and HRQoL of patients. In Spanish patients with XLH, the HRQoL was reduced despite conventional treatment, clearly indicating the need to improve the therapeutic approach to this disorder.

X-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affectingX-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affecting bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.

Controversias del tratamiento con hormona de crecimiento en pacientes con síndrome de Prader-Willi / Controversies in growth hormone treatment in patients with Prader-Willi syndrome

Introducción: El tratamiento con hormona de crecimiento (GH) en pacientes con síndrome de Prader-Willi (SPW) está aprobado en Europa desde 2001. A diferencia de otras indicaciones de la GH, su uso no solo está enfocado a incrementar la talla final, sino también a mejorar la composición corporal, la fuerza muscular y la capacidad cognitiva. Sin embargo, sigue habiendo dudas sobre los beneficios reales del tratamiento y sus potenciales efectos adversos. Este hecho limita en parte el uso de la GH, y dificulta que se beneficien de manera sistemática todos los pacientes susceptibles de ser tratados. Material y métodos: Se ha realizado una revisión de la literatura en Pubmed introduciendo "Prader-Willi" y "hormona de crecimiento" como palabras clave, en inglés y castellano, sin límite de fecha de publicación. Resultados: Se discuten los condicionantes que tradicionalmente han limitado el uso de la terapéutica con GH, y se actualizan ciertos aspectos controvertidos, como la edad de inicio del tratamiento y su prolongación en la edad de transición y la edad adulta. Conclusiones: El tratamiento con GH es seguro y eficaz en pacientes con SPW. La GH produce una mejora en el crecimiento, pero también aporta beneficios importantes en la composición corporal, el perfil metabólico y la función cognitiva. El inicio del tratamiento debería ser lo más precoz posible, preferiblemente antes del año de edad

Introduction: Treatment with growth hormone (GH) in patients with Prader Willi syndrome (PWS) has been approved in Europe since 2001. Unlike other GH indications, its use is not only focused on increasing final height, but also on improving body composition, muscular strength and cognitive capacity. However, there are still uncertainties regarding the real benefits of the treatment and its potential adverse effects. This partly limits the use of GH and prevents that every potential candidate systematically benefits from the treatment. Material and methods: A review of the literature was performed in Pubmed using «Prader Willi» and "growth hormone" as key words, in both English and Spanish, with no publication date limit. Results: Main conditioning factors that have traditionally limited the use of GH therapy are discussed and controversial aspects, such as age at treatment start and its continuation at the transition and adult age, are reviewed and updated. Conclusions: GH therapy is safe and effective in patients with PWS. GH not only improves linear growth but also provides significant benefits in body composition, metabolic profile and cognitive function. The onset of treatment should be as early as possible, preferably before one year of age