Impaired HDL-associated enzymes and proteins in children and adolescents with weight disorders and their association with novel cardiometabolic indexes.

BACKGROUND AND AIMS: Overweight/obesity (OW/OB) is associated with modifications in lipoprotein (Lp)-associated enzymes and proteins, such as cholesteryl ester transfer protein (CETP), Lp-associated phospholipase A2 (LpPLA2) and paraoxonase (PON)1. No evidence is available regarding underweight (UW). The following indexes have been proposed to better assess atherogenic risk related to weight alterations: triglycerides-glucose index (TyG), visceral adiposity index (VAI) and height-corrected lipid accumulation product (HLAP). AIM: To analyze the presence of alterations in Lp-associated enzymes and proteins in children and adolescents with UW and OW/OB and their relation to novel cardiometabolic indexes. METHODS AND RESULTS: Thirty male children and adolescents with UW, 66 with normal weight (NW) and 30 with OW/OB were included. Anthropometric parameters, glucose, Lp profile and the activities of CETP, LpPLA2 and PON1 were evaluated. Body mass index (BMI)-z, TyG, VAI and HLAP were calculated. UW and NW showed lower CETP activity than OW/OB (Mean ± SD) (218 ± 38vs.224 ± 26vs.237 ± 26%/mL.h; p < 0.05). UW and OW/OB showed lower PON1 activity than NW (318 ± 170vs.409 ± 200vs.310 ± 184 nmol/mL.min; p < 0.05). TyG was higher in OW/OB than UW (p < 0.01), whilst both HLAP (p < 0.05) and VAI (p < 0.01) followed a linear trend across weight categories. After adjusting for age and BMI-z, TyG was an independent predictor of CETP (r2 = 0.25, ß = -0.22, p < 0.01) and LpPLA2 (r2 = 0.21,ß = -0.21,p < 0.05), while VAI (r2 = 0.21,ß = -0.32,p < 0.01) and HLAP (r2 = 0.20,ß = -0.31,p < 0.01) of CETP. CONCLUSIONS: Both UW and OW/OB showed impaired antioxidant PON1 activity. Moreover, TyG, VAI and HLAP were all capable of predicting alterations in crucial modulators of Lp metabolism and vascular inflammation in children and adolescents with varying degrees of alterations in body weight.

Vascular inflammation and impaired reverse cholesterol transport and lipid metabolism in obese children and adolescents.

BACKGROUND AND AIMS: Childhood obesity is associated to complications such as insulin resistance and dyslipidemia. High density lipoproteins (HDL) constitute the only lipoprotein fraction with ateroprotective properties. The aim of the present study was to analyze inflammatory markers, carbohydrate metabolism, lipid profile and HDL functionality in obese children and adolescents compared to healthy controls. METHODS AND RESULTS: Twenty obese children and adolescents (Body mass index z score >3.0) (9-15 years old) and 20 age and sex similar controls were included in the study. Triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C, apolipoproteins (apo) A-I and B, glucose and insulin levels were quantified. Lipid indexes and HOMA-IR were calculated. Cholesterol efflux (CEC), lipoprotein associated phospholipase A2 (Lp-PLA2), lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein, plus paraoxonase and arylesterase (ARE) activities were evaluated. Obese children and adolescents showed significantly higher TG [69 (45-95) vs 96 (76-121); p < 0.05], non-HDL-C [99 ± 34 vs 128 ± 26; p < 0.01], TC/HDL-C [2.8 ± 0.6 vs 4.7 ± 1.5; p < 0.01], TG/HDL-C [1.1 (1.0-1.8) vs 2,2 (1.4-3.2); p < 0.01], and HOMA-IR [1.5 (1.1-1.9) vs. 2.6 (2.0-4.5); p < 0.01] values, plus Lp-PLA2 activity [8.3 ± 1.9 vs 7.1 ± 1.7 umol/ml.h; p < 0,05] in addition to lower HDL-C [57 ± 10 vs 39 ± 9; p < 0.01], apo A-I [143 ± 25 vs 125 ± 19; p < 0.05], and CEC [6.4 (5.1-6.8) vs. 7.8 (5.7-9.5); p < 0.01] plus LCAT [12.6 ± 3.3 vs 18.7 ± 2.6; p < 0.05] and ARE [96 ± 19 vs. 110 ± 19; p < 0.05] activities. Lp-PLA2 activity correlated with LDL-C (r = 0.72,p < 0.01), non-HDL-C (r = 0.76,p < 0.01), and apo B (r = 0.60,p < 0.01). LCAT activity correlated with triglycerides (r = -0.78,p < 0.01), HDL-C (r = 0.64,p < 0.01), and apo A-I (r = 0.62, p < 0.05). ARE activity correlated with HDL-C (r = 0.32,p < 0.05) and apoA-I (r = 0.43,p < 0.01). CEC was negatively associated with BMI z-score (r = -0.36,p < 0.05), and triglycerides (r = -0.28,p < 0.05), and positively with LCAT activity (r = 0.65,p < 0.05). In multivariate analysis, BMI z-score was the only parameter significantly associated to CEC (r2 = 0.43, beta = -0.38, p < 0.05). CONCLUSION: The obese group showed alterations in carbohydrate and lipid metabolism, which were associated to the presence of vascular specific inflammation and impairment of HDL atheroprotective capacity. These children and adolescents would present qualitative alterations in their lipoproteins which would determine higher risk of suffering premature cardiovascular disease.

High serum concentrations of dimeric inhibins A and B in normal newborn girls.

OBJECTIVE: To establish the serum pattern of dimeric inhibins in normal girls during the newborn period and to examine its relationship with the postnatal gonadotropic surge. DESIGN: Retrospective study. SETTING; Division of endocrinology of a children's hospital. PATIENT(S): Thirty-one girls 4 to 65 days of age. MAIN OUTCOME MEASURE(S): Serum levels of FSH, LH, and inhibin A and B. RESULT(S): High serum concentrations of both dimeric inhibins were detected during the first weeks of life. Concentrations tended to decrease through the second month of age. Inhibin A and B concentrations positively correlated with age only during the first 2 weeks of life (r =.57, P<.05 and r =.70, P<.01, respectively). Inhibin A and B were positively and significantly correlated with LH (r =.57, P<.05 and r =.52, P<.05, respectively) and with each other (r =.68, P<.0001). No correlation was found between dimeric inhibins and FSH. CONCLUSION(S): The high inhibin concentrations observed in newborn girls, which indicate advanced follicular development and granulosa cell differentiation, may be useful markers for congenital gonadal disorders.

Contribución de la determinación de tiroglobulina sérica al diagnóstico del hipotiroidismo congénito detectado por pesquisa neonatal / Contribution of serum thyroglobulin determination to the diagnosis of congenital hipothyroidism detected by neonatal screening

La tiroglobulina (TG) es la proteína tiroidea más abundante y constituye un precursor clave de la síntesis de la hormona tiroidea. Si no hay lesión tiroidea, los mayores factores determinantes del nivel de TG son la masa tiroidea y el estímulo de TSH.El objetivo fue determinar la utilidad de la TG sérica, medida por un método sensible, en la evaluación etiológica del hipotiroidismo congénito (HC) detectado por pesquisa neonatal.Se estudiaron 61 recién nacidos con HC, detectados por pesquisa neonatal. Se determinó TSH, T4, T3 por ECLIA, anticuerpos antitiroideos por radioligando (RSR) y TG por IFMA (límite de detección 9,0 ng/ml). Se determinó TG en 32 niños normales de 7 a 50 días como grupo control. Los niños con HC fueron clasificados por centellograma con Tc99 en 1)ectópicos, 2)atireóticos y 3) autópicos. Se realizó ecografía tiroidea.En el grupo control, los niveles de TG (ng/ml) fueron mediana (M) 41,5; percentilo 3 11,5 y percentilo 97 99,4. Los valores de TG (ng/ml) al diagnóstico en niños con HC fueron: 1) ectopia (n=28): M 135,5; rango 17,9-492; 2) atireóticos: 1) con ecografía coincidente (n= 12): M 0,58; rango 0,03-6; b) con ecografía discordante (n=5): M 65,2; rango 13,7-150 y 3) eutópicos: a) con bocio (n=11): M 1434,5; rango 306-2186, b) sin bocio (n=5): M 98,6; rango: 40,3-330.Conclusión: La TG sérica puede ser una herramiento útil para valorar el HC y orientar sobre su etiología a fin de contribuir a la investigación genética racional de defectos de formación y diferenciación tiroidea. El hallazgo de niveles de TG circulante normales en los pacientes con discordancia centello-ecográfica sugiere una mayor sensibilidad de la TG con respecto al centellograma en la detección de tejido tiroideo.

Contribución de la determinación de tiroglobulina sérica al diagnóstico del hipotiroidismo congénito detectado por pesquisa neonatal / Contribution of serum thyroglobulin determination to the diagnosis of congenital hipothyroidism detected by neonatal screening

La tiroglobulina (TG) es la proteína tiroidea más abundante y constituye un precursor clave de la síntesis de la hormona tiroidea. Si no hay lesión tiroidea, los mayores factores determinantes del nivel de TG son la masa tiroidea y el estímulo de TSH.El objetivo fue determinar la utilidad de la TG sérica, medida por un método sensible, en la evaluación etiológica del hipotiroidismo congénito (HC) detectado por pesquisa neonatal.Se estudiaron 61 recién nacidos con HC, detectados por pesquisa neonatal. Se determinó TSH, T4, T3 por ECLIA, anticuerpos antitiroideos por radioligando (RSR) y TG por IFMA (límite de detección 9,0 ng/ml). Se determinó TG en 32 niños normales de 7 a 50 días como grupo control. Los niños con HC fueron clasificados por centellograma con Tc99 en 1)ectópicos, 2)atireóticos y 3) autópicos. Se realizó ecografía tiroidea.En el grupo control, los niveles de TG (ng/ml) fueron mediana (M) 41,5; percentilo 3 11,5 y percentilo 97 99,4. Los valores de TG (ng/ml) al diagnóstico en niños con HC fueron: 1) ectopia (n=28): M 135,5; rango 17,9-492; 2) atireóticos: 1) con ecografía coincidente (n= 12): M 0,58; rango 0,03-6; b) con ecografía discordante (n=5): M 65,2; rango 13,7-150 y 3) eutópicos: a) con bocio (n=11): M 1434,5; rango 306-2186, b) sin bocio (n=5): M 98,6; rango: 40,3-330.Conclusión: La TG sérica puede ser una herramiento útil para valorar el HC y orientar sobre su etiología a fin de contribuir a la investigación genética racional de defectos de formación y diferenciación tiroidea. El hallazgo de niveles de TG circulante normales en los pacientes con discordancia centello-ecográfica sugiere una mayor sensibilidad de la TG con respecto al centellograma en la detección de tejido tiroideo. (AU)