Association between plasma leptin/adiponectin ratio and insulin resistance indexes in prepubertal children

ABSTRACT Objective: To assess the association between leptin/adiponectin ratio (LAR) and insulin resistance surrogates in prepubertal children. Subjects and methods: Study based on data from the Growth and Obesity Chilean Cohort Study (GOCS) involving 968 Chilean prepubertal children. Plasma insulin, leptin, and adiponectin were determined by immunoassays. Several common insulin resistance surrogates were calculated, including the homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride/HDL cholesterol index, triglyceride-glucose (TyG) index, and the TyG index corrected for body mass index (BMI; TyG-BMI) and waist circumference (WC; TyG-WC). Associations among variables were assessed using multiple linear and logistic regression analysis. Results: There was a significant direct association between plasma leptin and LAR with BMI z-score but no association between plasma adiponectin and adiposity. After adjustments for sex and age, LAR was significantly associated with all insulin resistance surrogates (which were categorized using the 75th percentile as the cutoff point), with the TyG-WC index emerging as the surrogate with the highest magnitude of association (odds ratio [OR] 2.44, 95% confidence interval [CI] 2.05-2.9). After additional adjustment for BMI z-score, only the association between LAR and TyG-WC remained significant (OR 1.64, 95% CI 1.27-2.12). Conclusion: Plasma leptin and LAR were strongly associated with several common insulin resistance surrogates in prepubertal children, most notably with the TyG-WC index. Associations between LAR and insulin resistance indexes were mainly driven by the effect of plasma leptin, which is also directly associated with increased adiposity.

Talla baja: enfoque diagnóstico y bases terapéuticas / Short stature: diagnostic approach and therapeutic basis

La talla baja es un motivo de consulta cada vez más frecuente que el pediatra debe pesquisar. La evaluación debe incluir una historia clínica completa, examen físico con una correcta evaluación auxológica y un seguimiento adecuado de la velocidad de crecimiento. De esta forma, los exámenes complementarios irán orientados a confirmar una sospecha diagnóstica. En países desarrollados la mayoría de los pacientes que consulta por talla baja corresponderá a retraso constitucional del crecimiento o a una talla baja familiar, sin embargo, en alrededor de un 5% de los casos estaremos frente a patología como por ejemplo desnutrición, malabsorción, enfermedades sistémicas y sus tratamientos, déficit de hormona de crecimiento y enfermedades genéticas entre otras. El enfoque terapéutico, debe estar siempre orientado a la causa. Existen terapias que pueden mejorar la estatura final pero tienen indicaciones precisas y no están exentas de complicaciones. Un estilo de vida saludable y un ambiente psicosocial favorable, permitirán que el niño desarrolle al máximo su potencial genético.

Short stature is a complaint of increasing frequency in pediatrics. Given the diverse etiology of growth failure, the pediatrician must be able to make a correct assessment of the growth and development of children, including a complete medical history, physical examination and a proper auxological assessment with a carefully monitoring of their growth rate. This way, any further examination shall be designed to confirm a diagnostic suspicion. Although most patients will have an idiopathic short stature, in about 5% of cases we will find pathology. The therapeutic approach should always be oriented to the cause. There are therapies that can improve the final height but have precise indications and are not exempt from complications. A healthy lifestyle and a positive psychosocial environment, allow the child to develop his full genetic potential.

Intereses y perspectiva sobre la carrera de medicina: un contraste entre estudiantes de medicina de primero y séptimo año / Interests and perspectives of first and last year medical students

Background: The interests that motivate medical students to study this career are diverse and they may change during the seven years of study. In Chile, 22 universities offer medicine and the number of graduated students has increased by more than 50% over the last 10 years. Aim: To determine the motivational profile of medical students at admission, and at the end of their career. Subjects and Methods: A voluntary anonymous survey was applied to 275 first and 140 seventh year medical students from one traditional public and two private schools. Results: The main reason for applying to medical school was social interest (68.7%), followed by interest in science and academia. Thirty six percent of students from seventh year would not study medicine again. In the seventh year, the interest in medical care persists in 88% of students, followed by academic interests in 64%. Only 24% had research interests. Fifty nine and 57% of students projected their medical work in private and public hospital settings, respectively. Only 11% projected themselves as doing research. Sixty nine percent of students would like to receive more information about post graduate education. Conclusions: There is a low interest in research and a high percentage of seventh year students that would not apply to medicine again. Medical schools should perform a systematic analysis of students' interests to improve faulty areas.

Metabolic syndrome in children born small-for-gestational age / Síndrome metabólica em crianças nascidas pequenas para a idade gestacional

Being born small-for-gestational age and a rapid increase in weight during early childhood and infancy has been strongly linked with chronic diseases, including metabolic syndrome, which has been related to intrauterine life environment and linked to epigenetic fetal programming. Metabolic syndrome includes waist circumference > 90th percentile for age, sex and race, higher levels of blood pressure, triglycerides and fasting glucose, and low levels of HDL-cholesterol. Insulin resistance may be present as early as 1 year of age, and obesity and/or type 2 diabetes are more prevalent in those born SGA than those born AGA. The programming of adaptive responses in children born SGA includes an association with increased blood pressure, changes in endothelial function, arterial properties and coronary disease. Early interventions should be directed to appropriate maternal nutrition, before and during pregnancy, promotion of breast feeding, and prevention of rapid weight gain during infancy, and to promote a healthy lifestyle.

Crianças nascidas pequenas para a idade gestacional (PIG) e um rápido ganho de peso durante a primeira e segunda infâncias estão fortemente ligados à ocorrência de doenças crônicas, incluindo a síndrome metabólica, o que está relacionado ao ambiente intrauterino e a alterações epigenéticas da programação fetal. A síndrome metabólica envolve uma circunferência abdominal > ao percentil 90 para a idade, sexo e raça, níveis mais altos de pressão sanguínea, triglicérides e glicose em jejum, e níveis baixos de HDL-colesterol. A resistência à insulina pode estar presente já no primeiro ano de vida, e a obesidade e/ou o diabetes tipo 2 são mais prevalentes em crianças nascidas PIG do que naquelas nascidas AIG. A programação de respostas adaptativas em crianças nascidas PIG inclui uma associação com uma pressão sanguínea mais alta, alterações na função endotelial e propriedades arteriais, e doença coronariana. Intervenções precoces devem ser direcionadas à nutrição apropriada, antes e durante a gravidez, promoção da amamentação e prevenção de ganho rápido de peso durante a infância e promoção de um estilo de vida saudável.

Mediciones de adiposidad intraabdominal por ultrasonido y factores asociados con riesgo cardiovascular en niños obesos / Ultrasound measurements of intra-abdominal adiposity and factors associated with cardiovascular risk in obese children

Background: Cardiovascular risk factors are commonly present in obese children. Aim: To evaluate the association among radiological measurements of intra-abdominal adipose tissue, and cardiovascular risk factors, in prepuberal obese children. Patients and Methods: We evaluated 30 obese (body mass index > p95) children aged 6 to 12 years (15 males). Anthropometry and blood pressure were measured. Subcutaneous and intra-abdominal fat thickness and fat area were measured by ultrasound (US) and computed tomography. Serum insulin, glucose and lipid profile were measured in a fasting blood sample. Homeostasis model assessment (HOMA) was calculated as an index of insulin resistance. Results: There was a significant correlation between US intra-abdominal fat thickness and HOMA (r = 0.47, p < 0.01), serum triglycerides (r = 0.46, p < 0.05) and with positive criteria for metabolic syndrome (r = 0.66, p < 0.01). A receiver operating curve (ROC) analysis showed that, above a cut-off of 45 mm for intra-abdominal fat thickness, US was able to identify insulin resistance with a sensibility and specificity of 79 and 69 percent respectively and metabolic syndrome with sensibility and specificity of 100 and 67 percent respectively. US and computed tomography measurements for intra-abdominal fat thickness were significantly correlated (r= 0.62, p < 0.01). Conclusions: US measurements of intra-abdominal fat thickness identify obesity-associated damage in childhood. Age-specific measurements of intra-abdominal adipose tissue may improve the detection power of this approach.

Síndrome de Satoyoshi: Enfermedad multisistémica con respuesta exitosa a tratamiento esteroidal / Satoyoshi syndrome: Report of one case

Satoyoshi  syndrome is a rare multisystemic disease of presumed autoimmune etiology characterized by progressive painful intermittent muscle spasms, diarrhea frequently associated with malabsorption, alopecia, skeletal abnormalities and endocrine disorders with a poor long-term prognosis due to early crippling. We report a 14-year-old Chilean girl with clinical and radiological features of the syndrome who has been successfully treated with prednisone and carbamazepine. She remarkably recovered from muscle spasms, alopecia and diarrhea. At follow up, 24 months later, she persists asymptomatic with considerable improvement in her quality of life.

Pubarquia precoz: Experiencia en 173 casos / Precocious pubarche: Experience in 173 cases

Background: Precocious pubarche (PP), defined as the development of sexual pubic hair before 8 years of age in females and before 9 years in males, is usually a benign condition but it can also be the first sign of an underlying disease. Aim: To analyze the etiology andperform a short term follow up in a cohort of patients with PP. Material and methods: A group of 173 patients (158 females) consulted for PP with a mean age of 7.4±0.1 years. These patients were followed between 15 to 60 months. Anthropometric measurements, bone age, serum levels of total testosterone, 17 OH progesterone (17 OHP) and dehydroepiandrosterone sulphate (DHEAS) were evaluated. Results: Mean birth weight and length was 3024.1±50.5 g and 48.5±0.3 cm,respectively. Ten percent of children were small for gestational age at birth. Bone age was accelerated by 1.1±0.01 years. One hundred and twelve patients were classified as having idiopathicPP (64.7%; 105 females), 29 as central precocious puberty (16.8%; only females), 16 as exaggerated adrenarche (EA 9.2%; 13 females) and 16 as non classical adrenal hyperplasia (9.2%; 11 females). Conclusions: PP represents a common and usually benign sign. However, 26% of cases had apathologic underlying condition. Therefore, all children with PP should be evaluated by a pediatric endocrinologist. Low birth weight was not frequent in this cohort and these patients did not show EA

Hipopituitarismo congénito: experiencia en 23 casos / Congenital hypopituitarism: report of 23 cases

Background: Congenital hypopituitarism is an uncommon cause of hypophyseal insufficiency It is less common than growth hormone deficiency which has an incidence of 1:4.000 to 1:8.000 Uve newborns. Early diagnosis ofthis condition is important to prevent impairment of cognitive function, poor growth and alterations in metabolic profile in these patients. Aim: To report 23 patients diagnosed with congenital hypopituitarism. Material and methods: Retrospective review of clinical records of 23 patients (12 males) with congenital hypopituitarism, diagnosed during a 21 years period. In a group of 16 patients a molecular study was performed searching for mutations in HESX1, PROP-1 or POUF-1. Results: Short stature was the most frequent sign at the first evaluation, followed by neonatal hypoglycemia and presence of nistagmus, strabismus, atrophic optic nerve or malformations in the middle Une showed in CNS imaging, suggesting septo-optic-dysplasia. All male patients diagnosed during neonatal period, exhibited micropenis. CNS images showed isolated hypophyseal hypoplasia or associated to an ectopic neurohypophysis in most patients. No patient in the subgroup subjected to molecular analysis had any of the mutations in the searched genes. Conclusions: The diagnosis of hypopituitarism must be based on clinical grounds, speciaUy when hypoglycemia, prolonged jaundice, micropenis or midline alterations are found in the neonatal period.

Adiposidad visceral y su asociación con lípidos séricos e insulinemis en adolescentes obesas / Visceral adiposity and its association with serum lipids in female obese teenagers

Background: Increased visceral or abdominal adipose tissue in children and adults is strongly associated with metabolic and a variety of chronic diseases. Aim: To study the association between visceral or external body measurements of adiposity with blood lipids, glucose and insulin levels, in obese female adolescents. Material and methods: In a cross-sectional study, 47 obese female adolescents (body mass index (BMI) >95th percentile) aged 10 to 15 years, were analyzed. Weight, height, BMI, Tanner pubertal stages, skinfold thickness, waist circumference, waist-to-hip ratio, fasting and 120 min post prandial blood glucose, serum insulin, and lipid profile were studied. Visceral fat was assessed by computed tomography at the L4-L5 level, measuring the fat area or the length of a straight drawn line between the spine and the internal border of the rectus abdominus muscle. Results: No association between lipid profile and BMI or external body measurements (skinfold thickness, waist circumference, waist-to-hip ratio) was observed. Total serum cholesterol >170 mg/dL was positively associated with the straight line over 63 mm (a cut-off obtained by ROC analysis (RR 2.64; 1.15-6.08). This association was statistically significant in girls in Tanner I + II (n =21; Fisher, p <0.023), but not with Tanner III + IV (n =26) stages. Increased cholesterol (>170 mg/dL) was also positively associated with a serum insulin >17 uU/mL in the Tanner I + II group (Fisher p<0.05), but not with the homeostasis model assessment of insulin resistance (HOMA). Conclusions: No external body measurement of adiposity was associated to increased serum cholesterol in these obese female adolescents. Increased total cholesterol (>170 mg/dL) was associated with visceral fat (evaluated through the straight line spina-rectus abdominus muscle), and also with a serum insulin >17 uU/ml in those teenagers with Tanner I or II pubertal stages.

Mediciones ultrasonográficas y de tomografía computada de adiposidad y alteraciones metabólicas asociadas a obesidad en niños / Measurements by ultrasound and computerized tomography of adiposity and metabolic complications of obesity

Introducción. La obesidad infantil es un problema de salud pública de prevalencia creciente y consecuencias a futuro. El compartimiento adiposo intraperitoneal estaría asociado a factores de riesgo metabólicos propios de la obesidad. No existe una estandarización de mediciones de tejido adiposo en imágenes en niños. Objetivos. Estudiar la asociación entre mediciones de tejido graso abdominal con insulinemia, en niños. Sujetos y Métodos. Se estudiaron 37 escolares prepuberales obesos (IMC ? p95), de ambos sexos, entre 6 y 12 años, con técnicas antropométricas, imagenológicas (US y TC) y de laboratorio (glicemia, insulinemia). Resultados. Las mediciones del tejido adiposo abdominal mediante US presentaron altas correlaciones con las mismas mediciones por TC (r= 0,79; p< 0,001). Las estimaciones de adiposidad visceral por US (r=0,56) y TC (r=0,53) tuvieron mejor correlación con insulinemia que las variables antropométricas, (IMC, r= 0,33; perímetro abdominal, r= 0,42). Conclusiones. La US aparece como una excelente herramienta disponible para la estimación de depósito adiposo intraperitoneal, que identifica de forma precoz alteraciones metabólicas asociadas a obesidad en niños.