Diagnosis accuracy of waist-to-height ratio to predict cardiometabolic risk in children with obesity.

BACKGROUND: Waist-to-height ratio (WHtR) predicts abdominal fat and cardiometabolic risk. In children with obesity, the most adequate cut-off to predict cardiometabolic risk as well as its ability to predict risk changes over time has not been tested. Our aim was to define an appropriate WHtR cut-off to predict cardiometabolic risk in children with obesity, and to analyze its ability to predict changes in cardiometabolic risk over time. METHODS: This is an observational prospective study secondary to the OBEMAT2.0 trial. We included data from 218 participants (8-15 years) who attended baseline and final visits (12 months later). The main outcome measure was a cardiometabolic risk score derived from blood pressure, lipoproteins, and HOMA index of insulin resistance. RESULTS: The optimal cut-off to predict the cardiometabolic risk score was WHtR ≥0.55 with an area under the curve of 0.675 (95% CI: 0.589-0.760) at baseline and 0.682 (95% CI: 0.585-0.779) at the final visit. Multivariate models for repeated measures showed that changes in cardiometabolic risk were significantly associated with changes in WHtR. CONCLUSION: This study confirms the clinical utility of WHtR to predict changes in cardiometabolic risk over time in children with obesity. The most accurate cut-off to predict cardiometabolic risk in children with obesity was WHtR ≥0.55. IMPACT: In children, there is no consensus on a unique WHtR cut-off to predict cardiometabolic risk. The present work provides sufficient evidence to support the use of the 0.55 boundary. We have a large sample of children with obesity, with whom we compared the previously proposed boundaries according to cardiometabolic risk, and we found the optimal WHtR cut-off to predict it. We also analyzed if a reduction in the WHtR was associated with an improvement in their cardiometabolic profile.

Pharmacological interventions for preventing complications in patients with idiopathic hypercalciuria: A systematic review / Intervenciones farmacológicas para prevenir complicaciones en pacientes con hipercalciuria idiopática: una revisión sistemática

Objective: To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria. Methods: We performed a search of multiple databases, trial registries, grey literature and conference proceedings up to October 2019. We included randomized and quasi-randomized controlled trials that examined any pharmacological intervention for preventing complications of idiopathic hypercalciuria (given for at least four months and six of follow-up). The primary outcomes were stone-free patients, urinary symptoms and severe adverse events. Results: We included five RCTs (n=446 patients, all adults, 4 in individuals with kidney stones and 1 in postmenopausal women with osteoporosis). Diuretics were likely to increase the number of stone-free patients (RR 1.61, 95% CI 1.33–1.96, moderate quality of evidence (QoE)); 274 more stone-free patients/1000 patients treated (95% CI: 148–432) and produced a slight decrease in the stone formation rate (mean difference −0.18, 95% CI −0.30 to −0.06, low QoE); 180 fewer stones/year/1000 patients treated (95% CI: 300 r to 60). No data on urinary symptoms were reported. The association between diuretic use and severe adverse events was uncertain (RR 5.00, 95% CI 0.60–41.88, very low QoE); 4 more severe adverse events/1000 patients treated (95% CI: 0 fewer to 39 more). Conclusions: The addition of diuretics to a normal or modified diet probably reduces the number of stone recurrences and may decrease the stone formation rate. It is uncertain whether diuretics increase the occurrence of severe adverse events. There were no studies investigating other outcomes or in children. (AU)

Objetivo: Evaluar los efectos de intervenciones farmacológicas en pacientes con hipercalciuria idiopática. Métodos: Realizamos una búsqueda en múltiples bases de datos, registros de ensayos, literatura gris y actas de congresos hasta octubre de 2019. Incluimos ensayos clínicos aleatorizados y cuasialeatorizados que examinaban cualquier intervención farmacológica para prevenir las complicaciones de la hipercalciuria idiopática (mínimo 4 meses de intervención y 6 meses de seguimiento). Los outcomes primarios fueron pacientes libres de cálculos, síntomas urinarios y efectos adversos graves. Resultados: Incluimos 5 RCT (n=446 pacientes, todos adultos, 4 en individuos con cálculos renales y uno en mujeres posmenopáusicas con osteoporosis). Los diuréticos aumentaban probablemente el número de pacientes libres de cálculos (RR 1,61; IC 95%: 1,33 a 1,96, moderada calidad de evidencia [QoE]); 274 más pacientes libres de cálculos/1.000 pacientes tratados (IC 95%: 148 a 432) y producían una ligera disminución en la tasa de formación de cálculos (diferencia media −0,18; IC 95%: −0,30 a −0,06, baja QoE); 180 menos cálculos/año/1.000 pacientes tratados (IC 95%: 300 a 60). No se informaron datos sobre síntomas urinarios. La asociación entre el uso de diuréticos y los efectos adversos graves fue incierta (RR 5,00; IC 95%: 0,60 a 41,88, muy baja QoE); 4 efectos adversos severos más/1.000 pacientes tratados (IC 95%: 0 a 39). Conclusiones: Los diuréticos añadidos a una dieta normal o modificada probablemente reducen la aparición de cálculos y pueden disminuir su tasa de formación. Es incierto si los diuréticos incrementan la ocurrencia de efectos adversos graves. No se encontraron estudios que investigaran otros outcomes o realizados en niños. (AU)

Validation of an Algorithm for the Prediction of Diabetic Retinopathy in Type 1 Diabetic Patients in a Spanish Population.

Aim: The aim of the present study was to build a clinical decision support system (CDSS) that can predict the presence of diabetic retinopathy (DR) in type 1 diabetes (T1DM) patients. Material and Method: We built two versions of our CDSS to predict the presence of any-type DR and sight-threatening DR (STDR) in T1DM patients. The first version was trained using 324 T1DM and 826 T2DM patients. The second was trained with only the 324 T1DM patients. Results: The first version achieved an accuracy (ACC) = 0.795, specificity (SP) = 83%, and sensitivity (S) = 65.7% to predict the presence of any-DR, and an ACC = 0.918, SP = 87.1% and S = 87.8% for STDR. The second model achieved ACC = 0.799, SP = 87.5% and S = 86.3% when predicting any-DR and ACC = 0.937, SP = 90.9% and S = 83.0% for STDR. Conclusion: The two models better predict STDR than any-DR in T1DM patients. We will need a larger sample to strengthen our results.

Pharmacological interventions for preventing complications in patients with idiopathic hypercalciuria: A systematic review.

OBJECTIVE: To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria. METHODS: We performed a search of multiple databases, trial registries, grey literature and conference proceedings up to October 2019. We included randomized and quasi-randomized controlled trials that examined any pharmacological intervention for preventing complications of idiopathic hypercalciuria (given for at least four months and six of follow-up). The primary outcomes were stone-free patients, urinary symptoms and severe adverse events. RESULTS: We included five RCTs (n=446 patients, all adults, 4 in individuals with kidney stones and 1 in postmenopausal women with osteoporosis). Diuretics were likely to increase the number of stone-free patients (RR 1.61, 95% CI 1.33-1.96, moderate quality of evidence (QoE)); 274 more stone-free patients/1000 patients treated (95% CI: 148-432) and produced a slight decrease in the stone formation rate (mean difference -0.18, 95% CI -0.30 to -0.06, low QoE); 180 fewer stones/year/1000 patients treated (95% CI: 300 r to 60). No data on urinary symptoms were reported. The association between diuretic use and severe adverse events was uncertain (RR 5.00, 95% CI 0.60-41.88, very low QoE); 4 more severe adverse events/1000 patients treated (95% CI: 0 fewer to 39 more). CONCLUSIONS: The addition of diuretics to a normal or modified diet probably reduces the number of stone recurrences and may decrease the stone formation rate. It is uncertain whether diuretics increase the occurrence of severe adverse events. There were no studies investigating other outcomes or in children.

Pharmacological interventions for preventing complications in patients with idiopathic hypercalciuria: A systematic review.

OBJECTIVE: To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria. METHODS: We performed a search of multiple databases, trial registries, grey literature and conference proceedings up to October 2019. We included randomized and quasi-randomized controlled trials that examined any pharmacological intervention for preventing complications of idiopathic hypercalciuria (given for at least four months and six of follow-up). The primary outcomes were stone-free patients, urinary symptoms and severe adverse events. RESULTS: We included five RCTs (n=446 patients, all adults, 4 in individuals with kidney stones and 1 in postmenopausal women with osteoporosis). Diuretics were likely to increase the number of stone-free patients (RR 1.61, 95% CI 1.33-1.96, moderate quality of evidence (QoE)); 274 more stone-free patients/1000 patients treated (95% CI: 148-432) and produced a slight decrease in the stone formation rate (mean difference -0.18, 95% CI -0.30 to -0.06, low QoE); 180 fewer stones/year/1000 patients treated (95% CI: 300 r to 60). No data on urinary symptoms were reported. The association between diuretic use and severe adverse events was uncertain (RR 5.00, 95% CI 0.60-41.88, very low QoE); 4 more severe adverse events/1000 patients treated (95% CI: 0 fewer to 39 more). CONCLUSIONS: The addition of diuretics to a normal or modified diet probably reduces the number of stone recurrences and may decrease the stone formation rate. It is uncertain whether diuretics increase the occurrence of severe adverse events. There were no studies investigating other outcomes or in children.

The Effect of HbA1c Variability as a Risk Measure for Microangiopathy in Type 1 Diabetes Mellitus.

BACKGROUND: To measure the relationship between variability in HbA1c and microalbuminuria (MA) and diabetic retinopathy (DR) in the long term. METHODS: A prospective case-series study, was conducted on 366 Type 1 Diabetes Mellitus patients with normoalbuminuria and without diabetic retinopathy at inclusion. The cohort was followed for a period of 12 years. The Cox survival analysis was used for the multivariate statistical study. The effect of variability in microangiopathy (retinopathy and nephropathy) was evaluated by calculating the standard deviation of HbA1c (SD-HbA1c), the coefficient of variation of HbA1c (CV-HbA1c), average real variability (ARV-HbA1c) and variability irrespective of the mean (VIM-HbA1c) adjusted for the other known variables. RESULTS: A total of 106 patients developed diabetic retinopathy (29%) and 73 microalbuminuria (19.9%). Overt diabetic nephropathy, by our definition, affected only five patients (1.36%). Statistical results show that the current age, mean HbA1c, SD-HbA1c and ARV-HbA1c are significant in the development of diabetic retinopathy. Microalbuminuria was significant for current age, mean HbA1c, CV-HbA1c and ARV-HbA1c. CONCLUSIONS: By measuring the variability in HbA1c, we can use SD-HbA1c and ARV-HbA1c as possible targets for judging which patients are at risk of developing DR and MA, and CV-HbA1c as the target for severe DR.

Validation of bioelectrical impedance analysis for body composition assessment in children with obesity aged 8-14y.

BACKGROUND & AIMS: The aim was to generate a predictive equation to assess body composition (BC) in children with obesity using bioimpedance (BIA), and avoid bias produced by different density levels of fat free mass (FFM) in this population. METHODS: This was a cross-sectional validation study using baseline data from a randomized intervention trial to treat childhood obesity. Participants were 8 to 14y (n = 315), underwent assessments on anthropometry and BC through Air Displacement Plethysmography (ADP), Dual X-Ray Absorptiometry and BIA. They were divided into a training (n = 249) and a testing subset (n = 66). In addition, the testing subset underwent a total body water assessment using deuterium dilution, and thus obtained results for the 4-compartment model (4C). A new equation to estimate FFM was created from the BIA outputs by comparison to a validated model of ADP adjusted by FFM density in the training subset. The equation was validated against 4C in the testing subset. As reference, the outputs from the BIA device were also compared to 4C. RESULTS: The predictive equation reduced the bias from the BIA outputs from 14.1% (95%CI: 12.7, 15.4) to 4.6% (95%CI: 3.8, 5.4) for FFM and from 18.4% (95%CI: 16.9, 19.9) to 6.4% (95% CI: 5.3, 7.4) for FM. Bland-Altman plots revealed that the new equation significantly improved the agreement with 4C; furthermore, the observed trend to increase the degree of bias with increasing FM and FFM also disappeared. CONCLUSION: The new predictive equation increases the precision of BC assessment using BIA in children with obesity.

A novel approach to assess body composition in children with obesity from density of the fat-free mass.

BACKGROUND & AIMS: Assessment of Fat Mass (FM) and fat-free mass (FFM) using Air-displacement plethysmography (ADP) technique assumes constant density of FFM (DFFM) by age and sex. It has been recently shown that DFFM further varies according to body mass index (BMI), meaning that ADP body composition assessments of children with obesity could be biased if DFFM is assumed to be constant. The aim of this study was to validate the use of the calculations of DFFM (rather than constant density of the FFM) to improve accuracy of body composition assessment in children with obesity. METHODS: cross-sectional validation study in 66 children with obesity (aged 8-14 years) where ADP assessments of body composition assuming constant density (FFMBODPOD and FMBODPOD) were compared to those where DFFM was adjusted in relation to BMI (FFMadjusted and FMadjusted), and both compared to the gold standard reference, the 4-component model (FFM4C and FM4C). RESULTS: FFMBODPOD was overestimated by 1.50 kg (95%CI -0.68 kg, 3.63 kg) while FFMadjusted was 0.71 kg (-1.08 kg, 2.51 kg) (percentage differences compared to FFM4C were 4.9% (±2.9%) and 2.8% (±2.1%), respectively (p < 0.001)). Consistently, FM was underestimated by both methods, representing a mean difference between methods of 4.0% (±2.9%) and 6.8% (±3.8%), respectively, when compared to the reference method. The agreement and reliability of body composition assessments were improved when adjusted using calculations (adjusted models) rather than assuming constant DFFM. CONCLUSIONS: The use of constant values for fat-free mass properties may increase bias when assessing body composition (FM and FFM) in children with obesity by two-component techniques such as ADP. Using adjusted corrections as proposed in the present work may reduce the bias by half.

Efficacy of therapeutic lifestyle changes on lipid profiles assessed by NMR in children with familial and non-familial hypercholesterolemia / Eficacia de los cambios terapéuticos en el estilo de vida en el perfil lipídico evaluado por RMN en niños con hipercolesterolemia familiar y no familiar

Background and aims: The first line of therapy in children with hypercholesterolaemia is therapeutic lifestyle changes (TLSC). The efficacy of lifestyle intervention in children with familial hypercholesterolaemia (FH), where LDL-C levels are genetically driven, deserves a focused study. Aims: To evaluate the impact of a lifestyle education program, focused on food patterns and physical activity, on lipid profiles assessed by nuclear magnetic resonance (NMR) in children with FH vs. non-FH. Methods: Phase 1 was a cross-sectional study of baseline characteristics, and phase 2 was a prospective TLSC intervention study. In total, the study included 238 children (4 to 18 years old; 47% girls) attending the lipid unit of our hospital due to high cholesterol levels. Eighty-five were diagnosed with FH (72% genetic positive), and 153 were diagnosed with non-Familial hypercholesterolaemia. A quantitative food frequency questionnaire (FFQ) including 137 items was used. Physical activity (PA) was assessed by the Minnesota questionnaire. The lipid profile was assessed using the 2D-1H-NMR (Liposcale test). A total of 127 children (81 in the FH group) participated in the prospective phase and were re-assessed after 1 year of the TLSC intervention, consisting of education on lifestyle changes delivered by a specialized nutritionist. Results: The FH and non-FH groups were similar in anthropometry and clinical data, except that those in the FH were slightly younger than those in the non-FH group. Both the FH and non-FH groups showed a similar diet composition characterized by a high absolute calorie intake and a high percentage of fat, mainly saturated fat. The PA was below the recommended level in both groups. After one year of TLSC, the percentage of total and saturated fats was reduced, and the amount of fiber increased significantly in both groups. The percentage of protein increased slightly. The number of children engaged in at least 1 hour/day of PA increased by 56% in the FH group and by 53% in the non-FH group, and both these increases were significant. The total and small-LDL particle numbers were reduced in both groups, although the absolute change was greater in the FH group than in the non-FH group. Conclusions: Educational strategies to implement TLSC in children lead to empowerment, increased adherence, and overall metabolic improvement in children with high blood cholesterol, including those with FH

Antecedentes y objetivos: La primera línea de terapia en niños con hipercolesterolemia son los cambios terapéuticos en el estilo de vida (TLSC). La eficacia de la intervención en el estilo de vida en niños con hipercolesterolemia familiar (HF), en los que los niveles de LDL-C son generados genéticamente, merece un estudio específico. Objetivos: Evaluar el impacto de un programa de educación sobre el estilo de vida, centrado en los patrones alimentarios y la actividad física, sobre el perfil lipídico evaluado por resonancia magnética nuclear (RMN) en niños con HF versus no HF. Métodos: La fase 1 fue un estudio transversal de las características basales, y la fase 2 fue un estudio prospectivo de intervención mediante TLSC. En total, el estudio incluyó a 238 niños (de 4 a 18 años; 47% niñas) que asistieron a la unidad de lípidos de nuestro hospital debido a los altos niveles de colesterol. Ochenta y cinco fueron diagnosticados con HF (72% genéticamente positivos), y 153 fueron diagnosticados de no HF. Se utilizó un cuestionario cuantitativo de frecuencia de alimentos (FFQ) que incluye 137 ítems. La actividad física (AF) se evaluó mediante el cuestionario de Minnesota. El perfil lipídico se evaluó mediante la prueba 2D-1H-NMR (Liposcale Test). Un total de 127 niños (81 en el grupo HF) participaron en la fase prospectiva y fueron reevaluados después de 1 año de la intervención mediante TLSC, que consistió en educación sobre cambios en el estilo de vida impartida por una nutricionista especializada. Resultados: Los grupos HF y no HF fueron similares en los datos antropométricos y clínicos, excepto que los HF eran ligeramente más jóvenes que los no HF. Los participantes de ambos grupos mostraron una composición de dieta similar caracterizada por un alto consumo de calorías totales y un alto porcentaje de grasas, principalmente grasas saturadas. La AF estuvo por debajo del nivel recomendado en ambos grupos. Después de un año de TLSC, se redujo el porcentaje de grasas totales y saturadas, y la cantidad de fibra aumentó significativamente en ambos grupos. El porcentaje de proteína aumentó ligeramente. El número de niños involucrados en al menos 1 hora/día de AF aumentó en un 56% en el grupo de HF y en un 53% en el grupo sin HF, y ambos aumentos fueron significativos. Los números de partículas LDL totales y pequeñas se redujeron en ambos grupos, aunque el cambio absoluto fue mayor en el grupo HF que en el grupo no HF. Conclusiones: Las estrategias educativas para implementar TLSC en niños conducen al empoderamiento, al aumento de la adherencia y a la mejora metabólica general en niños con colesterol alto en sangre, incluidos aquellos con HF

Efficacy of therapeutic lifestyle changes on lipid profiles assessed by NMR in children with familial and non-familial hypercholesterolemia.

BACKGROUND AND AIMS: The first line of therapy in children with hypercholesterolaemia is therapeutic lifestyle changes (TLSC). The efficacy of lifestyle intervention in children with familial hypercholesterolaemia (FH), where LDL-C levels are genetically driven, deserves a focused study. AIMS: To evaluate the impact of a lifestyle education program, focused on food patterns and physical activity, on lipid profiles assessed by nuclear magnetic resonance (NMR) in children with FH vs. non-FH. METHODS: Phase 1 was a cross-sectional study of baseline characteristics, and phase 2 was a prospective TLSC intervention study. In total, the study included 238 children (4 to 18 years old; 47% girls) attending the lipid unit of our hospital due to high cholesterol levels. Eighty-five were diagnosed with FH (72% genetic positive), and 153 were diagnosed with non-Familial hypercholesterolaemia. A quantitative food frequency questionnaire (FFQ) including 137 items was used. Physical activity (PA) was assessed by the Minnesota questionnaire. The lipid profile was assessed using the 2D-1H-NMR (Liposcale test). A total of 127 children (81 in the FH group) participated in the prospective phase and were re-assessed after 1 year of the TLSC intervention, consisting of education on lifestyle changes delivered by a specialized nutritionist. RESULTS: The FH and non-FH groups were similar in anthropometry and clinical data, except that those in the FH were slightly younger than those in the non-FH group. Both the FH and non-FH groups showed a similar diet composition characterized by a high absolute calorie intake and a high percentage of fat, mainly saturated fat. The PA was below the recommended level in both groups. After one year of TLSC, the percentage of total and saturated fats was reduced, and the amount of fiber increased significantly in both groups. The percentage of protein increased slightly. The number of children engaged in at least 1 hour/day of PA increased by 56% in the FH group and by 53% in the non-FH group, and both these increases were significant. The total and small-LDL particle numbers were reduced in both groups, although the absolute change was greater in the FH group than in the non-FH group. CONCLUSIONS: Educational strategies to implement TLSC in children lead to empowerment, increased adherence, and overall metabolic improvement in children with high blood cholesterol, including those with FH.

The Obemat2.0 Study: A Clinical Trial of a Motivational Intervention for Childhood Obesity Treatment.

The primary aim of the Obemat2.0 trial was to evaluate the efficacy of a multicomponent motivational program for the treatment of childhood obesity, coordinated between primary care and hospital specialized services, compared to the usual intervention performed in primary care. This was a cluster randomized clinical trial conducted in Spain, with two intervention arms: motivational intervention group vs. usual care group (as control), including 167 participants in each. The motivational intervention consisted of motivational interviewing, educational materials, use of an eHealth physical activity monitor and three group-based sessions. The primary outcome was body mass index (BMI) z score increments before and after the 12 (+3) months of intervention. Secondary outcomes (pre-post intervention) were: adherence to treatment, waist circumference (cm), fat mass index (z score), fat free mass index (z score), total body water (kg), bone mineral density (z score), blood lipids profile, glucose metabolism, and psychosocial problems. Other assessments (pre and post-intervention) were: sociodemographic information, physical activity, sedentary activity, neuropsychological testing, perception of body image, quality of the diet, food frequency consumption and foods available at home. The results of this clinical trial could open a window of opportunity to support professionals at the primary care to treat childhood obesity. The clinicaltrials.gov identifier was NCT02889406.

Detecting familial hypercholesterolemia earlier in life by actively searching for affected children:The DECOPIN project.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is underdiagnosed in children. We assessed a combination of two screening methods. The first method was to detect hypercholesteraemic children and then study the parents (Ch-P pathway), and the second one was to study the offspring of FH-affected parents (P-Ch pathway). METHODS: In the Ch-P path, primary care paediatricians were asked to include lipid profiling or, at least, total cholesterol (TC) and then lipid profiling if TC was higher than 5.2 mmol/L in any clinically indicated blood test. Children with LDL-C ≥ 3.5 mmol/L, plus either a family history of early cardiovascular disease or one parent with severe hypercholesterolemia, were referred to the lipid unit where the parents, rather than their children, were studied. In parents with definite, clinical FH, a genetic study was performed. Focused genetic testing was performed on all offspring of genetically positive parents. The P-Ch path consisted of the active study of children from definite FH adults. RESULTS: Fifty-nine paediatricians covering a total population of 63,616 children agreed to participate in the project. Of the 216 children (122 Ch-P and 94 P-Ch) who were ultimately referred to the lipid unit, 87 children with FH (84% genetically positive) were identified. Additionally, 41 parents (from 40 families) were newly diagnosed with FH (63% genetically positive). Forty-nine different mutations were detected: 46 in the LDLR, 2 in the PCSK9 and 1 in APOB gene. CONCLUSIONS: The implementation of active strategies to detect FH in children, in close collaboration with primary care paediatricians, provides a high-performance method for early FH detection.

Valor de los parámetros lipídicos y apoproteicos para la detección de hipercolesterolemia familiar en la infancia. Proyecto DECOPIN / Lipid and lipoprotein parameters for detection of familial hypercholesterolemia in childhood. The DECOPIN Project

Introducción: La hipercolesterolemia familiar (HF) infantil está infradiagnosticada y su diagnóstico no es fácil en la práctica clínica. El objetivo fue evaluar qué características clínicas, bioquímicas y de imagen vascular pueden ayudarnos a detectar a niños/as y adolescentes con hipercolesterolemia afectados de HF. Métodos: Doscientos veintidós niños y adolescentes de entre 4 y 18 años fueron reclutados para participar en un proyecto de detección precoz de HF (proyecto DECOPIN). La HF se diagnosticó por criterios genéticos o clínicos. Se definió hipercolesterolemia poligénica (HP) cuando el c-LDL >135mg/dl pero sin criterios clínicos ni genéticos de HF. Participantes con c-LDL < 135mg/dl se incluyeron en el grupo control (GC). Se recogieron la historia familiar, los datos antropométricos y las variables clínicas. Se analizaron parámetros bioquímicos y lipídicos. Se determinó el grosor íntima-media carotídeo (GIMc) y los tendones de Aquiles por ecografía. Resultados: Noventa y un niños fueron diagnosticados de HF y 23 de HP, y 108 como GC. El grupo HF presentó mayores concentraciones de CT, c-LDL, índice ApoB/ApoA1 e índice colesterol año. El c-HDL fue menor en grupo HF que en el GC. Si bien el c-LDL fue el parámetro más definitorio de HF, el índice ApoB/ApoA1 > 0,82 fue el que de forma aislada mostró mayor sensibilidad y especificad para predecir la presencia de mutación en el grupo de niños HF. El grosor de los tendones de Aquiles no mostró diferencias entre grupos. El GIMc fue mayor en los niños HF sin diferencias significativas. Conclusiones: Los niveles de c-LDL son el marcador de HF. Un índice ApoB/ApoA1 > 0,82 puede ser una herramienta útil para decidir el estudio genético en niños con sospecha de HF

Background: Familial hypercholesterolaemia (FH) in children is under-detected and is difficult to diagnose in clinical practice. The aim of this study was to evaluate clinical, biochemical and vascular imaging variables in order to detect children and adolescents with FH. Methods: A total of 222 children aged 4-18 years old were recruited to participate in a project for the early detection of FH (The DECOPIN Project). They were distributed into 3groups: FH, if genetic study or clinical criteria were positive (n=91); Polygenic hypercholesterolaemia (PH) if LDL-Cholesterol >135mg/dL without FH criteria (n=23), and Control group (CG) if LDL-C <135mg/dL (n=108). Data were collected from family history, anthropometric data, and clinical variables. The usual biochemical parameters, including a complete lipid profile were analysed. The carotid intima-media thickness (cIMT) and thickness of Achilles tendons were determined using ultrasound in all participants. Results: A total of 91 children had a diagnosis of FH, 23 with PH, and 108 with CG. Children with FH had higher concentrations of total cholesterol, LDL-C, ApoB/ApoA1 ratio, and cholesterol-year score, than the other groups. HDL-C was lower in the FH group than in the CG. Thickness of the Achilles tendon and cIMT did not show any differences between groups, although a greater cIMT trend was observed in the FH group. ApoB/ApoA1 ratio >0.82 was the parameter with the highest sensitivity and specificity to predict the presence of mutation in children with FH. Conclusions: Although LDL-C is the main biochemical parameter used to define FH, the ApoB/ApoA1 ratio (>0.82) may be a useful tool to identify children with FH and a positive mutation

Lipid and lipoprotein parameters for detection of familial hypercholesterolemia in childhood. The DECOPIN Project. / Valor de los parámetros lipídicos y apoproteicos para la detección de hipercolesterolemia familiar en la infancia. Proyecto DECOPIN.

BACKGROUND: Familial hypercholesterolaemia (FH) in children is under-detected and is difficult to diagnose in clinical practice. The aim of this study was to evaluate clinical, biochemical and vascular imaging variables in order to detect children and adolescents with FH. METHODS: A total of 222 children aged 4-18 years old were recruited to participate in a project for the early detection of FH (The DECOPIN Project). They were distributed into 3groups: FH, if genetic study or clinical criteria were positive (n=91); Polygenic hypercholesterolaemia (PH) if LDL-Cholesterol >135mg/dL without FH criteria (n=23), and Control group (CG) if LDL-C <135mg/dL (n=108). Data were collected from family history, anthropometric data, and clinical variables. The usual biochemical parameters, including a complete lipid profile were analysed. The carotid intima-media thickness (cIMT) and thickness of Achilles tendons were determined using ultrasound in all participants. RESULTS: A total of 91 children had a diagnosis of FH, 23 with PH, and 108 with CG. Children with FH had higher concentrations of total cholesterol, LDL-C, ApoB/ApoA1 ratio, and cholesterol-year score, than the other groups. HDL-C was lower in the FH group than in the CG. Thickness of the Achilles tendon and cIMT did not show any differences between groups, although a greater cIMT trend was observed in the FH group. ApoB/ApoA1 ratio >0.82 was the parameter with the highest sensitivity and specificity to predict the presence of mutation in children with FH. CONCLUSIONS: Although LDL-C is the main biochemical parameter used to define FH, the ApoB/ApoA1 ratio (>0.82) may be a useful tool to identify children with FH and a positive mutation.

Lipoprotein profile assessed by 2D-1H-NMR and subclinical atherosclerosis in children with familial hypercholesterolaemia.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is underdiagnosed in children. In addition to lipid concentrations, lipoprotein particle quantity and quality could influence cardiovascular risk. We aimed to perform a comprehensive plasma lipid study, including lipoprotein particle number and size assessment by two-dimensional nuclear magnetic resonance (2D-1H-NMR), in children with FH compared to non-affected children and to evaluate the clinical value of these factors as subclinical atherosclerosis biomarkers. METHODS: One hundred eighty-three children participating in the broad "Hypercholesterolemia Early Detection Programme" (Decopin Project) were recruited. They were categorized as FH, if they had either a positive genetic test or clinical certainty, or as control children (CCh). Medical history, anthropometry and clinical variables were recorded. Standard biochemical measurements were performed. The lipoprotein profile was studied by 2D-1H-NMR. Carotid intima-media thickness (cIMT) was assessed by sonography in 177 children. RESULTS: FH children had a significant 36% increase in LDL particles. The small LDL fraction was increased by 33% compared to CCh. The relative relationship between large, medium and small LDL and the mean LDL particle size was similar between FH children and CCh. The total and small LDL particle numbers were directly associated with and contributed to the determination of the mean cIMT according to bivariate and multivariate analyses in FH children. CONCLUSIONS: The higher cholesterol levels of FH children are due to an overall increased number of all LDL particle subclasses, including a notable 33% increase in small LDL. Total and small LDL particle number shows a good correlation with cIMT in FH children.

Plasma inducible degrader of the LDLR, soluble low-density lipoprotein receptor, and proprotein convertase subtilisin/kexin type 9 levels as potential biomarkers of familial hypercholesterolemia in children.

BACKGROUND: Familial hypercholesterolemia (FH) in children is under-detected. Plasma biomarkers associated with low-density lipoprotein receptor (LDLR) function could help identifying FH children. OBJECTIVES: We aim to assess the clinical value of inducible degrader of the LDLR (IDOL), soluble LDLR (sLDLR), and proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma concentrations in children with FH compared with control children (CCh). METHODS: This was a cross-sectional study performed in a Lipid Unit from a University hospital. The participants were 177 children distributed into FH (n = 77) and CCh (n = 100). Main outcomes were changes in IDOL, sLDLR, and PCSK9 plasma concentrations between children groups; secondary outcomes were the association between IDOL, sLDLR, and PCSK9 and lipid profile determined by 2-dimensional nuclear magnetic resonance. RESULTS: The IDOL levels were higher in FH compared with CCh (P = .007). The PCSK9 levels were elevated in FH (P < .001). The sLDLR levels had no significant differences between groups. IDOL was significantly positively associated to total and LDL cholesterol and ApoB100 but not to LDL particle number. However, a robust correlation with Lp(a) (P = .001) was observed. PCSK9 had the strongest correlation with LDL-associated parameters including particle number. sLDLR was associated with triglyceride levels (P < .001) and triglyceride-rich particles and inversely to LDL size. CONCLUSIONS: The IDOL and PCSK9 plasma levels are significantly higher in FH children. Interestingly, sLDLR was associated with atherogenic dyslipidemia components. IDOL concentrations show a robust association with Lp(a) levels. To study the role of plasma biomarkers associated with LDLR expression in FH is warranted.

Initial Approach to Childhood Obesity in Spain. A Multisociety Expert Panel Assessment.

PURPOSE: In recent years, the incidence of childhood obesity in Europe, and Spain in particular, has increased dramatically. Bariatric surgery could play a major role in treating of adolescents with severe obesity. However, no specific guidelines for bariatric surgery currently exist in Spain. METHODS: The Board of the Spanish Society for Obesity Surgery and Metabolic Diseases (SECO) proposed a study of childhood obesity by using the Delphi method. This prospective study involved 60 experts from nine national societies. Each society leader recruited experts from their society in obesity-related fields. Two online questionnaires were taken, and consensus on guidelines for various obesity treatments was reached according to the percentage of answers in favor or against inclusion of a given guideline. Based on these results, preoperative, surgical management and follow-up of childhood obesity management among others were analyzed. RESULTS: The survey results indicated significant concern among all societies regarding obesity. There was strong consensus with regard to adolescents and obesity, medical treatment, dietary recommendations, environmental and social factors, and goals for adolescents with obesity. Consensus on the use of intragastric balloons and other techniques was not reached. However, biliopancreatic diversion was rejected as a primary treatment, and mandatory psychological/psychiatric assessment was agreed upon. Inclusion criteria accepted were similar to those for adults with the exception of surgery in those with a body mass index <40. CONCLUSIONS: Spanish obesity-related societies are aware of the societal problem of childhood obesity. Multisociety development of national approaches may arise from consensus-building studies among specialists.

[Obesity associated metabolic impairment is evident at early ages: Spanish collaborative study]. / Las alteraciones metabólicas asociadas a la obesidad están ya presentes en los primeros años de vida: estudio colaborativo español.

UNLABELLED: The objectives of this study are to provide a description of the demographic, anthropometric characteristics and metabolic abnormalities in children with early-onset (< 10 years) and of very-early-onset obesity (< 5 years). We also evaluate the diagnostic ability using the definition of metabolic syndrome (MS) according to different criteria. METHODS: It is a retrospective, case-control, cross-sectional, multicenter study. A total of 10 Pediatric Endocrinology Units in different Spanish hospitals were involved. A group of 469 children with early-onset obesity and another group of 30 children with very early-onset obesity were studied. The control group consisted of 224 healthy children younger than 10 years. Anthropometric and analytical determination of carbohydrates metabolism parameters and the lipid profile were performed. RESULTS: The presence of metabolic alterations associated with obesity in children and adolescents in Spain is remarkable, either on their own, or encompassed within the definition of MS. This prevalence increases substantially when considering the peripheral resistance to insulin action as a diagnostic criterion. It also shows how children who could not be diagnosed with MS according to the definition provided by the International Diabetes Federation (IDF) due to age below 10 years, these alterations are already present in a remarkable percentage. In fact, metabolic abnormalities are already present in the very-early-onset obese children ( <5 years). CONCLUSION: In Spanish children there are metabolic alterations associated with obesity in the infant-juvenile stages alone or encompassed within the definition of MS,and are already present at earlier ages.

Los objetivos de este estudio son, realizar una descripción de las características demográficas, antropométricas y de las alteraciones metabólicas de niños atendidos por obesidad resaltando las características aquellos casos de obesidad de inicio temprano (< 10 años) y los de inicio precoz (< 5 años), y evaluar la capacidad diagnóstica de la definición de síndrome metabólico (SM) según diferentes criterios. Métodos: Es un estudio retrospectivo, caso-control, transversal, multicéntrico. Han participado un total de 10 Unidades de Endocrinología Pediátrica de diferentes hospitales españoles con un grupo de 469 niños con obesidad de inicio temprano y otro grupo de 30 niños con obesidad de inicio precoz. El grupo control estuvo constituido por 224 niños sanos menores de 10 años. Se realizó una valoración antropométrica y determinación analítica de parámetros del metabolismo de los hidratos de carbono y lipidograma. Resultados: La presencia de alteraciones metabólicas asociadas a la obesidad en la etapa infanto-juvenil en España es notable, de forma aislada, o englobada bajo la definición de SM. La prevalencia de éste aumenta sustancialmente cuando se considera la resistencia periférica a la acción de la insulina como criterio diagnóstico. Se demuestra cómo en niños menores de 10 años, dichas alteraciones están presentes en un porcentaje reseñable, y se encuentran las primeras alteraciones metabólicas ya en niños obesos < 5 años. Conclusión: En los niños españoles existen alteraciones metabólicas asociadas a la obesidad en la etapa infanto- juvenil de forma aislada o englobada bajo la definición de SM, y ya están presentes a edades precoces.

Las alteraciones metabólicas asociadas a la obesidad están ya presentes en los primeros años de vida: estudio colaborativo español / Obesity associated metabolic impairment is evident at early ages: Spanish collaborative study

Los objetivos de este estudio son, realizar una descripción de las características demográficas, antropométricas y de las alteraciones metabólicas de niños atendidos por obesidad resaltando las características aquellos casos de obesidad de inicio temprano (< 10 años) y los de inicio precoz (< 5 años), y evaluar la capacidad diagnóstica de la definición de síndrome metabólico (SM) según diferentes criterios. Métodos: Es un estudio retrospectivo, caso-control, transversal, multicéntrico. Han participado un total de 10 Unidades de Endocrinología Pediátrica de diferentes hospitales españoles con un grupo de 469 niños con obesidad de inicio temprano y otro grupo de 30 niños con obesidad de inicio precoz. El grupo control estuvo constituido por 224 niños sanos menores de 10 años. Se realizó una valoración antropométrica y determinación analítica de parámetros del metabolismo de los hidratos de carbono y lipidograma. Resultados: La presencia de alteraciones metabólicas asociadas a la obesidad en la etapa infanto-juvenil en España es notable, de forma aislada, o englobada bajo la definición de SM. La prevalencia de éste aumenta sustancialmente cuando se considera la resistencia periférica a la acción de la insulina como criterio diagnóstico. Se demuestra cómo en niños menores de 10 años, dichas alteraciones están presentes en un porcentaje reseñable, y se encuentran las primeras alteraciones metabólicas ya en niños obesos < 5 años. Conclusión: En los niños españoles existen alteraciones metabólicas asociadas a la obesidad en la etapa infanto-juvenil de forma aislada o englobada bajo la definición de SM, y ya están presentes a edades precoces (AU)

The objectives of this study are to provide a description of the demographic, anthropometric characteristics and metabolic abnormalities in children with early-onset (< 10 years) and of very-early-onset obesity (< 5 years). We also evaluate the diagnostic ability using the definition of metabolic syndrome (MS) according to different criteria. Methods: It is a retrospective, case-control, cross-sectional, multicenter study. A total of 10 Pediatric Endocrinology Units in different Spanish hospitals were involved. A group of 469 children with early-onset obesity and another group of 30 children with very early-onset obesity were studied. The control group consisted of 224 healthy children younger than 10 years. Anthropometric and analytical determination of carbohydrates metabolism parameters and the lipid profile were performed. Results: The presence of metabolic alterations associated with obesity in children and adolescents in Spain is remarkable, either on their own, or encompassed within the definition of MS. This prevalence increases substantially when considering the peripheral resistance to insulin action as a diagnostic criterion. It also shows how children who could not be diagnosed with MS according to the definition provided by the International Diabetes Federation (IDF) due to age below 10 years, these alterations are already present in a remarkable percentage. In fact, metabolic abnormalities are already present in the very-early-onset obese children (<5 years). Conclusion: In Spanish children there are metabolic alterations associated with obesity in the infant-juvenile stages alone or encompassed within the definition of MS, and are already present at earlier ages (AU)