Association between long telomere length and insulin sensitization in adolescent girls with hyperinsulinemic androgen excess

Research letterThe centile of telomere length from early adulthood until senescence is mainly set between early gestation and adolescence.1 Hyperinsulinemic androgen excess (HIAE) is the most prevalent endocrinopathy of adolescent girls and is frequently driven by an absolute or relative excess of fat.2 Hyperinsulinemic androgen excess in adolescence is associated with a higher risk for a broad range of endocrine, metabolic, and cardiovascular complications later in life.

Postnatal anthropometric and body composition profiles in infants with intrauterine growth restriction identified by prenatal doppler

Introduction: Infant anthropometry and body composition have been previously assessed to gauge the impact of intrauterine growth restriction (IUGR) at birth, but the interplay between prenatal Doppler measurements and postnatal development has not been studied in this setting. The present investigation was performed to assess the significance of prenatal Doppler findings relative to postnatal anthropometrics and body composition in IUGR newborns over the first 12 months of life. Patients and methods: Consecutive cases of singleton pregnancies with suspected IUGR were prospectively enrolled over 12 months. Fetal biometry and prenatal Doppler ultrasound examinations were performed. Body composition was assessed by absorptiometry at ages 10 days, and at 4 and12 months. Results: A total of 48 pregnancies qualifying as IUGR were studied. Doppler parameters were normal in 26 pregnancies. The remaining 22 deviated from normal, marked by an Umbilical Artery Pulsatility Index (UA-PI) >95th centil or Cerebro-placental ratio (CPR) <5th centile. No significant differences emerged when comparing anthropometry and body composition at each time point, in relation to Doppler findings. Specifically, those IUGR newborns with and without abnormal Doppler findings had similar weight, length, body mass index, lean and fat mass, and bone mineral content throughout the first 12 months of life. In a separate analysis, when comparing IUGR newborns by Doppler (abnormal UA-PI vs. abnormal CPR), anthropometry and body composition did not differ significantly. Conclusions: Infants with IUGR maintain a pattern of body composition during the first year of life that is independent of prenatal Doppler findings. Future studies with larger sample sizes and correlating with hormonal status are warranted to further extend the phenotypic characterization of the various conditions now classified under the common label of IUGR

Placental and cord blood methylation of genes involved in energy homeostasis: association with fetal growth and neonatal body composition.

Low weight at birth associates with subsequent susceptibility to diabetes. Epigenetic modulation is among the mechanisms potentially mediating this association. We performed a genome-wide DNA methylation analysis in placentas from term infants born appropriate-for-gestational-age (AGA) or small-for-gestational-age (SGA), to identify new genes related to fetal growth and neonatal body composition. Candidate genes were validated by bisulfite pyrosequencing (30 AGA, 21 SGA) and also analyzed in cord blood. Gene expression analyses were performed by RT-PCR. Neonatal body composition was assessed by dual X-ray absorptiometry at age 2 weeks. The ATG2B, NKX6.1 and SLC13A5 genes (respectively related to autophagy, beta-cell development and function, and lipid metabolism) were hypermethylated in placenta and cord blood from SGA newborns, whereas GPR120 (related to free fatty acid regulation) was hypomethylated in placenta and hypermethylated in cord blood. Gene expression levels were opposite to methylation status, and both correlated with birth weight, with circulating IGF-I, and with total and abdominal fat at age 2 weeks. In conclusion, alterations in methylation and expression of genes involved in the regulation of energy homeostasis were found to relate to fetal growth and neonatal body composition, and may thus be among the early mechanisms modulating later susceptibility to diabetes

Specific Dietary Components and Gut Microbiota Composition are Associated with Obesity in Children and Adolescents with Prader-Willi Syndrome

Prader-Willi syndrome is a rare genetic disorder associated with impaired body composition, hyperphagia, and excessive weight gain. Strict dietary restrictions from an early age is crucial to prevent or delay the early onset of obesity, which is the main driver of comorbidities in these patients. The aim of this study was to identify dietary and gut microbiota components closely linked to weight status of these patients. We studied a cohort of children and adolescents with genetic diagnosis of Prader-Willi syndrome (N = 31), in which we determined adiposity by Dual-energy X-ray absorptiometry (DXA) and dietary composition with 4-day food records. Furthermore, we obtained fecal samples to assess microbiota composition by 16S sequencing. Multivariate regression models showed that body mass index standard deviation score (BMI-SDS) and body fat mass were directly associated with saturated fat intake and meat consumption, and inversely associated with fruit consumption. Furthermore, the gut microbiome from normal weight patients was characterized by higher phylogenetic diversity compared to those overweight or obese, with differential abundance of several genera, including Alistipes, Klebsiella, and Murimonas. Notably, Alistipes abundance was inversely correlated to adiposity, lipid and glucose homeostasis parameters, and meat intake. Our results suggest that limiting meat and increasing fruit intake might be beneficial for body weight management in children and adolescents with Prader-Willi syndrome

Estudio prospectivo de maduración, desarrollo e incidencia lesional en balonmano formativo de élite. ¿Puede el estado madurativo ser un factor determinante de la incidencia lesional en balonmano?

El objetivo de este estudio es describir la relación entre incidencia lesional (IL) y estado madurativo de jugadores varones de balonmano formativo (BmF) de alto nivel competicional. Se analizan durante 2 temporadas la incidencia de lesión deportiva de forma prospectiva en 133 jugadores, los criterios de maduración biológica y la carga física de exposición. Se siguieron los criterios para estudios de epidemiología lesional según el consenso UEFA. Las variables utilizadas para analizar el estado madurativo son los estadios de Tanner, la pubertad, el pico de velocidad de crecimiento, el volumen testicular y la edad ósea. Se registraron 190 lesiones para un total de 34.222 h de exposición. La IL total media de todas las categorías fue de 5,6 lesiones/1.000 h de exposición. En competición, el valor fue de 21,8 lesiones/1.000 h, y en entrenamiento, de 3,1 lesiones/1.000 h. No se encontraron diferencias estadísticamente significativas entre IL, la edad cronológica y los diferentes estados madurativos por ANOVA. El análisis estadístico multivariante registra cierta tendencia entre las asociaciones de IL en competición para categoría (p = 0,07), y en la IL en entrenamientos para Tanner (p = 0,091) y pubertad (p = 0,021). En conclusión, si bien no se detectaron diferencias significativas en la IL por edades en jugadores de BmF, sí se aprecia una tendencia real en determinados estadios madurativos mediante el análisis multivariante. Esto deberá tenerse en cuenta para planificación entrenamientos y estrategias de prevención de la lesión deportiva en el contexto del BmF

Estudi prospectiu de maduració, desenvolupament i incidència lesional en l’handbol formatiu d’elit. L’estadi maduratiu pot ser un factor determinant d’incidència lesional a l’handbol?

L’objectiu d’aquest estudi és descriure la relació entre incidència lesional (IL) i estat maduratiu de jugadors homes d’handbol formatiu (HbF) d’alt nivell competitiu. Durant 2 temporades s’analitza la incidència de la lesió esportiva de forma prospectiva, els criteris de maduració biològica i la càrrega física d’exposició, de 133 jugadors. Se seguiren els criteris del consens UEFA sobre estudis d’epidemiologia lesional. Les variables utilitzades per analitzar l’estat maduratiu foren els estadis de Tanner, la pubertat, el pic de velocitat de creixement, el volum testicular i l’edat òssia. Es registraren 190 lesions en un total de 34.222 h d’exposició. La IL total mitjana de totes las categories fou de 5,6 lesions/1.000 h d’exposició. Durant la competició, el valor fou de 21,8 lesions/1.000 h, i en l’entrenament de 3,1 lesions/1.000 h. No es trobaren diferències estadísticament significatives entre IL, edat cronològica i els diferents estadis maduratius en l’ANOVA. L’anàlisi estadística multivariant registrà una certa tendència a associar la IL en la categoria competició (p = 0,07), i la IL en entrenament en Tanner (p = 0,091) i pubertat (p = 0,021). En conclusió, tot i que no es detectaren diferències significatives en la IL per edat en jugadors d’HbF, s’aprecia una tendència real en determinats estadis maduratius mitjançant l’anàlisi multivariant, cosa que caldria que es tingués en compte per planificar entrenaments i estratègies de prevenció de lesions esportives en el context de l’HbF

Circulating fatty acid synthase in pregnant women: relationship to blood pressure, maternal metabolism and newborn parameters.

The enzyme FASN (fatty acid synthase) is potentially related with hypertension and metabolic dysfunction. FASN is highly expressed in the human placenta. We aimed to investigate the relationship circulating FASN has with blood pressure, maternal metabolism and newborn parameters in healthy pregnant women. Circulating FASN was assessed in 115 asymptomatic pregnant women in the second trimester of gestation along with C-peptide, fasting glucose and insulin, post-load glucose lipids, HMW-adiponectin and blood pressure (the latter was assessed in each trimester of gestation). At birth, newborns and placentas were weighed. FASN expression was also able to be assessed in 80 placentas. Higher circulating FASN was associated with lower systolic blood pressure (SBP), with a more favourable metabolic phenotype (lower fasting glucose and insulin, post load glucose, HbAc1, HOMA-IR and C-peptide), and with lower placental and birth weight (all p < 0.05 to p < 0.001). Placental FASN expression related positively to circulating FASN (p < 0.005) and negatively to placental weight (p < 0.05). Our observations suggest a physiological role of placental FASN in human pregnancy. Future studies will clarify whether circulating FASN of placental origin does actually regulate placental and fetal growth, and (thereby) has a favourable influence on the pregnant mother's insulin sensitivity and blood pressure

Serum alkaline phosphatase relates to cardiovascular risk markers in children with high calcium-phosphorus product

Although alkaline phosphatase (ALP) correlates with cardiovascular risk in adults, there are no studies in children. We evaluated the association between serum ALP levels, calcium-phosphorus product (Ca*P) and cardiovascular risk markers in healthy children. Children aged 7.9 ± 1.4 (n = 379) were recruited in this cross-sectional study. The main outcome measures were systolic and diastolic blood pressure (SBP and DBP) and carotid intima-media thickness (cIMT). Additional assessments were body-mass index (BMI), waist circumference, homeostatic model assessment of insulin resistance (HOMA-IR) and fasting lipids, ALP, serum calcium, phosphorus and Ca*P. ALP was directly correlated with BMI (p < 0.0001), waist circumference (p < 0.0001), SBP (p < 0.0001), cIMT (p = 0.005), HOMA-IR (p < 0.0001), and fasting triglycerides (p = 0.0001). Among them, in children with Ca*P values above the median the associations were BMI (r = 0.231; p = 0.001), waist (r = 0.252; p < 0.0001), SBP (r = 0.324; p < 0.0001), cIMT (r = 0.248; p = 0.001) and HOMA-IR (r = 0.291; p < 0.0001)]. ALP independently associated with SBP (β = 0.290, p < 0.001) and cIMT (β = 0.179, p = 0.013) in children with higher Ca*P, after adjusting for confounding variables. Circulating ALP is associated with a more adverse cardiovascular profile in children with higher Ca*P. We suggest that serum ALP and Ca*P levels could contribute to the assessment of risk for cardiovascular disease in children

Catch-up growth in juvenile rats, fat expansion, and dysregulation of visceral adipose tissue

BACKGROUND: Accelerated catch-up growth following intrauterine restriction increases the risk of developing visceral adiposity and metabolic abnormalities. However, the underlying molecular mechanisms of such metabolic programming are still poorly understood. METHODS: A Wistar rat model of catch-up growth following intrauterine restriction was used. A gene expression array was performed in the retroperitoneal adipose tissue sampled at postnatal day (PD) 42. RESULTS: Five hundred and forty-six differentially expressed genes (DEGs) were identified (adjusted p value < 0.05). Gene ontology enrichment analysis identified pathways related to immune and lipid metabolic processes, brown fat cell differentiation, and regulation of PI3K. Ccl21, Npr3, Serpina3n, Pnpla3, Slc2a4, and Serpina12 were validated to be upregulated in catch-up pups (all p < 0.01) and related to several fat expansion and metabolic parameters, including body weight at PD42, postnatal body weight gain, white and brown adipose tissue mass, plasma triglycerides, and insulin resistance index (all p < 0.05). CONCLUSIONS: Genes related to immune and metabolic processes were upregulated in retroperitoneal adipose tissue following catch-up growth in juvenile rats and were found to be associated with fat expansion and metabolic parameters. Our results provide evidence for several dysregulated genes in white adipose tissue that could help develop novel strategies to prevent the metabolic abnormalities associated with catch-up growth

Associations between genetic obesity susceptibility and early postnatal fat and lean mass: an individual participant meta-analysis

IMPORTANCE: Patterns of body size and body composition associated with genetic obesity susceptibility inform the mechanisms that increase obesity risk. OBJECTIVE: To test associations between genetic obesity susceptibility, represented by a combined obesity risk-allele score, and body size or body composition at birth to age 5 years. DESIGN, SETTING, AND PARTICIPANTS: A total of 3031 children from 4 birth cohort studies in England, France, and Spain were included in a meta-analysis. EXPOSURES: A combined obesity risk-allele score was calculated from genotypes at 16 variants identified by genome-wide association studies of adult body mass index (BMI). MAIN OUTCOMES AND MEASURES: Outcomes were age- and sex-adjusted SD scores (SDS) for weight, length/height, BMI, fat mass, lean mass, and percentage of body fat at birth as well as at ages 1, 2 to 3, and 4 to 5 years. RESULTS: The obesity risk-allele score was not associated with infant size at birth; at age 1 year it was positively associated with weight (β [SE], 0.020 [0.008] SDS per allele; P = .009) and length (β [SE], 0.020 [0.008] SDS per allele; P = .01), but not with BMI (β [SE], 0.013 [0.008] SDS per allele; P = .11). At age 2 to 3 years these associations were stronger (weight: β [SE], 0.033 [0.008] SDS per allele; P  .15 at all ages). CONCLUSIONS AND RELEVANCE: Genetic obesity susceptibility appears to promote a normally partitioned increase in early postnatal, but not prenatal, growth. These findings suggest that symmetrical rapid growth may identify infants with high life-long susceptibility for obesity