Mariela Paoli

Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus.

We recently demonstrated that children with type 1 diabetes mellitus (DM) have decreased lumbar spine bone mineral density (BMD) as early as four years after clinical diagnosis of the disease. In order to determine whether osteopenia is already present in patients very early on after diagnosis of clinical DM, we evaluated the bone mineral status of a group of newly diagnosed children (5.8 +/- 1.5 mo after diagnosis). We studied 23 prepubertal children (7 M, 16 F) with a mean chronological age of 9.5 +/- 2.2 yr and a mean glycosylated hemoglobin of 8.9 +/- 2.4%. Lumbar spine and femoral neck BMD were measured by dual X-ray absorptiometry, while bone turnover was assessed by the determination of the serum concentration of the carboxy-terminal propeptide of type I collagen (PICP) and the carboxy-terminal cross-linked telopeptide of type I collagen (N-telopeptide). Results were compared to those of age, height, and pubertal status matched controls. Lumbar spine BMD Z-scores were decreased in patients compared to controls (Z-scores of -0.89 +/- 1.2, with 10 of 22 patients showing values >1 SD below the mean). When lumbar spine Z-scores were analyzed in those patients with <3 months or > or =3 months since diagnosis of DM a significant difference was noticed between groups (-0.648 +/- 1.12 vs -1.267 +/- 1.17; p <0.02). No significant differences were noted in femoral neck BMD and total BMD between groups. Serum PICP levels were decreased when compared to controls (233.6 +/- 39.3 vs 375.9 +/- 50.7 microg/l; p <0.002), while serum N-telopeptide concentrations, although increased, were not significantly different (9.3 +/- 1.3 vs 5.7 +/- 1.5 microg/l). In summary, early on after the diagnosis of type 1 DM, children present with decreased lumbar spine BMD and decreased bone formation markers.

Cardiovascular risk of young growth-hormone-deficient adolescents. Differences in growth-hormone-treated and untreated patients.

Objective: To determine whether postprandial lipids, coagulation factors and homocysteine levels are abnormal in young growth hormone (GH)-deficient (GHD) adolescents. Methods: Fifteen GHD adolescents on GH replacement were studied. Ten untreated GHD adolescents and 15 healthy subjects served as controls. Fasting lipids, lipoprotein(a), fibrinogen, plasminogen activator inhibitor-1, homocysteine, folate and vitamin B12 levels were measured. Cholesterol and triglycerides were measured 4 h after a high fat meal. Results: Fasting and postprandial triglycerides and homocysteine levels of untreated GHD patients were increased compared to those of GH-treated GHD subjects and healthy controls; fibrinogen concentrations were elevated in both treated and untreated adolescents. Conclusions: GHD adolescents present an abnormal fasting and postprandial lipid profile. In addition, the increased fibrinogen and homocysteine levels are suggestive of the accumulation of cardiovascular risk factors early on in life.

Bone Mineral Density of Prepubertal Age Girls with Turner’s Syndrome While on Growth Hormone Therapy

Bone mineral densities and growth velocities of young girls with Turners syndrome treated with recombinant human growth hormone at an age before the decreased levels of estrogens secondary to their ovarian failure could contribute to osteopenia were studied. Twelve patients with a mean chronological age of 8.9 +/- 0.9 years and a mean bone age of 6.9 +/- 0.8 years received growth hormone therapy for over 2 years (0.5 IU/kg/week s.c.) Mean growth velocities increased significantly from a baseline level of 3.5 +/- 0.4 cm/year to 6.4 +/- 0.3 and 5.7 +/- 0.4 cm/year at 12 and 24 months of therapy, while height SDS improved from -3.1 +/- 0.4 at baseline to -2.7 +/- 0.3 and -2.4 +/- 0.3 at 12 and 24 months, respectively. Total bone calcium as well as cortical bone mineral density of our density of our patients while on recombinant human growth hormone were similar to that of a control group of prepubertal healthy growth children paired for bone age and height; bone density of trabecular bone was however increased in our patients when compared to healthy controls (0.791 +/- 0.04 vs. 0.669 +/- 0.02 g/cm2; p < 0.025). We conclude from our study that the bone mineral status of young girls with Turners syndrome on growth hormone therapy seems to be normal.

Effectiveness and limitations of the use of the gonadotropin-releasing hormone agonist leuprolide acetate in the diagnosis of delayed puberty in males.

In order to evaluate the effectiveness of the gonadotropin-releasing hormone agonist leuprolide acetate in distinguishing gonadotropin deficiency from delayed puberty, a single subcutaneous dose of 20 micrograms/kg of leuprolide acetate was administered at 07.00 h to 14 patients with constitutionally delayed puberty and to 8 gonadotropin-deficient subjects, and serum gonadotropin and testosterone levels were determined at baseline and 1,2,3,6,12, and 24 h thereafter. The increase in gonadotropin and testosterone levels was significant in patients with delayed puberty, so that the mean peak luteinizing hormone and to a lesser degree the mean peak testosterone levels clearly differentiated normally delayed from gonadotropin-deficient puberty. However, when the peak gonadotropin and testosterone concentrations were analyzed individually, there was a considerable overlap between the two groups of males, limiting the usefulness of this test.

Valores de referencia de la circunferencia de la cintura e índice de la cintura/cadera en escolares y adolescentes de Mérida, Venezuela: comparación con referencias internacionales

OBJECTIVEnTo collect regional reference values of waist circumference (WC), and waist/hip ratio (WHR) in children and adolescents from Merida, Venezuela, and to compare them to international references.nnnSUBJECTS AND METHODSnA total of 919 students aged 9-17 years from public and private educational establishments were assessed. Weight, height, WC, and WHR were measured. Outliers (± 3 SD Z-Score) were excluded from the data collected. Percentile distribution of the tested variables was done by age and sex.nnnRESULTSnFifty-one percent of subjects were female, and 52.7% were from public institutions. WC (p=0.001) and WHR (p=0.0001) were statistically higher in boys. With advancing age, WC increased in both sexes, while WHR showed the opposite behavior (p=0.0001 for both). The 90th percentile (pc) for WC ranged from 69.7 and 83.6 cm in girls and from 69.2 and 86.7 cm in boys. The 90th pc values of WHR ranged from 0.79 and 0.91 in girls and from 0.86 and 0.93 in boys. Overall, our WC and WHR values were lower than North American values and similar to those of some Latin American references.nnnCONCLUSIONnPercentile reference charts for WC and WHR specific for age and sex, obtained from a representative sample of children and adolescents from Mérida, Venezuela, are provided. They may be used regionally, both for individual assessment and to implement prevention policies.

Effect of Glycemic Control on the Growth Velocity and Several Metabolic Parameters of Conventionally Treated Children with Insulin Dependent Diabetes Mellitus

To determine the effect of glycemic control on the growth velocity and several metabolic parameters of children with insulin-dependent diabetes mellitus (IDDM), 79 patients with IDDM, 45 females and 34 males with a mean chronological age of 8.4 +/- 3.0 years were followed over a 5-year period starting at the onset of diabetes. Glycemic control was assessed by measuring total glycosylated hemoglobin; children were divided into better controlled, GHb < 9%, 30 children (Group A) and worse controlled, GHb > or = 9%, 49 patients (Group B). Growth velocity was significantly lower, in the five years of follow up, in the worse controlled patients when compared to the better controlled subjects (4.8 +/- 1.6 vs 6.7 +/- 2.2 cm/yr after the first year and 5.0 +/- 2.0 vs 6.5 +/- 1.8 cm/yr after the fifth year, in group B and group A, respectively). Higher cholesterol (185.3 +/- 33.7 vs 158.8 +/- 39.5 mg/dl) and triglyceride levels (85.9 +/- 43.5 vs 71.0 +/- 37.4 mg/dl) were apparent in the worse controlled patients, when compared to the better controlled children. Insulin dose was not significantly different in the two groups (0.76 +/- 0.3 vs 0.84 +/- 0.4 U/kg/day in the 1st year and 0.9 +/- 0.3 vs 0.92 +/- 0.4 U/kg/day in the 5th year, in group B and A respectively). Although both groups received the same initial and long term training by our pediatric diabetes team, more frequent blood glucose monitoring, better record keeping and rotation of injection sites and more clinic visits were clearly noted in the better controlled group. Ketoacidotic episodes were more common in the worse controlled patients, while better controlled children had a higher number of hypoglycemic episodes. In conclusion, we have found poor glycemic control, as reflected by higher glycosylated hemoglobin levels, to affect the growth velocity and several metabolic parameters of children with diabetes followed for a five-year period. Other factors besides insulin dose and initial and subsequent diabetic education seem to play a role in their glycemic control.

Limited Weight Loss or Simply No Weight Gain following Lifestyle-Only Intervention Tends to Redistribute Body Fat, to Decrease Lipid Concentrations, and to Improve Parameters of Insulin Sensitivity in Obese Children.

Objectives. To investigate whether lifestyle-only intervention in obese children who maintain or lose a modest amount of weight redistributes parameters of body composition and reverses metabolic abnormalities. Study Design. Clinical, anthropometric, and metabolic parameters were assessed in 111 overweight or obese children (CA of 11.3 ± 2.8 years; 63 females and 48 males), during 8 months of lifestyle intervention. Patients maintained or lost weight (1–5%) (group A; n: 72) or gained weight (group B). Results. Group A patients presented with a decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP) ( and , resp.), BMI (), z-score BMI (), waist circumference (), fat mass (), LDL-C (), Tg/HDL-C ratio (), fasting and postprandial insulin (), and HOMA (), while HDL-C () and QUICKI increased (). Conversely, group B patients had an increase in BMI (), waist circumference (), SBP (), and in QUICKI (), while fat mass (), fasting insulin (), and HOMA () decreased. Lean mass, DBP, lipid concentrations, fasting and postprandial glucose, postprandial insulin, and ultrasensitive C-reactive protein (CRP) remained stable. Conclusions. Obese children who maintain or lose a modest amount of weight following lifestyle-only intervention tend to redistribute their body fat, decrease blood pressure and lipid levels, and to improve parameters of insulin sensitivity.

Relación triglicéridos/colesterol de la lipoproteína de alta densidad como indicador de riesgo cardiometabólico en niños y adolescentes de la ciudad de Mérida, Venezuela

OBJECTIVEnTo determine the behavior of the triglycerides/HDL-cholesterol ratio (TG/HDL) as a cardiometabolic risk marker in children and adolescents from Mérida, Venezuela.nnnMETHODSnA total of 1292 children and adolescents aged 7-18 years who attended educational institutions in the Libertador Municipality were enrolled into this study. Anthropometric measurements and blood pressure values were recorded. Fasting blood glucose, insulin and lipid levels were measured. The TG/HDL ratio, HOMA-IR, and QUICKI indexes were calculated. Subjects were categorized as with and without cardiometabolic risk based on the presence or absence of 2or more risk factors. Cut-off points for the TG/HDL ratio were determined by constructing ROC curves.nnnRESULTSnSignificantly higher mean TG/HDL ratios were found in pubertal (2.2 ± 1.7) as compared to prepubertal subjects (1.8 ± 1.5; P=.001), with no sex differences. Two or more risk factors were found in 14.7% (n=192) of the participants, in whom TG/HDL ratios were significantly higher as compared to those with no risk (3.5±2.9 versus 1.6±0.8 in prepubertal and 4.1 ± 3.5 versus 1.8 ± 0.9 in pubertal subjects; P=.0001). According to cardiometabolic risk, cut-off points for the TG/HDL ratio of 1.8 and 2.5xa0were found for prepubertal and pubertal children respectively. These cut-off points showed risks (odds ratio) higher than 2.5 for conditions such as metabolic syndrome, elevated non-HDL-C, abdominal obesity, and elevated HOMA-IR.nnnCONCLUSIONnIn this sample of children and adolescents, an elevated TG/HDLc ratio was found to be a good marker for predicting cardiometabolic risk.

Respuesta a Carta a: Valores de referencia de la circunferencia de la cintura e índice de la cintura/cadera en escolares y adolescentes de Mérida, Venezuela: comparación con referencias internacionales

Hemos leído con detenimiento los comentarios de la carta al editor en relación con nuestro artículo publicado recientemente. Efectivamente, el estudio fue realizado en el Municipio Libertador del Estado Mérida, como bien se señala en la sección de Material y Métodos, y forma parte de un proyecto denominado «Evaluación del crecimiento, desarrollo y factores de riesgo cardiometabólico en escolares y adolescentes de Mérida, Venezuela (CREDEFAR)». En acuerdo con los comentarios de la carta al editor, se debe evitar cualquier confusión del lector desde el inicio de cualquier artículo, por lo que se tomará en cuenta esta recomendación y se escribirá la procedencia del Municipio Libertador, Mérida, Venezuela, en el título de futuras comunicaciones de CREDEFAR. Nuestro estudio es observacional de corte transversal. Se ratifica que tanto los institutos educativos como los escolares y adolescentes que participaron fueron seleccionados en forma aleatorizada y siguiendo una rigurosa planificación, tal como se señala en el artículo: «La muestra se seleccionó aplicando un muestreo por estratificación, proporcional, aleatorizado y polietápico que garantizaba la participación adecuada por sexo, por institución pública o privada (condición socioeconómica) y por ubicación geográfica». La población a estudiar era aproximadamente de 4.000 escolares y adolescentes para cada año de edad, según la información suministrada por la zona educativa del Estado Mérida. Con relación al cálculo del tamaño de la muestra, esta fue estimada según la media de circunferencia de cintura de 58 cm y desviación estándar de 10 cm, obtenida en estudio previo realizado en nuestra ciudad, con un error alfa del 5%, error beta del 20%, precisión del 2% y potencia a priori del 80%. Este tamaño de muestra fue de 94 participantes por cada año de edad, esto es un total de 846 escolares y adolescentes de 9 a 17-18 años. Como se evidencia, se superó este tamaño de muestra, ya que en nuestro estudio fueron incluidos 919 estudiantes. La potencia a posteriori fue del 96,63%. Además, se realizaron los cálculos necesarios para asegurar que este tamaño de muestra fuera

Leptina en relación con el sexo, el índice de masa corporal, el estadio puberal y la insulina en niños con déficit de hormonas de crecimiento con y sin tratamiento sustitutivo

Introduccion En este estudio nos proponemos investigar las concentraciones de leptina y su relacion con el sexo, el indice de masa corporal, el estadio puberal y las concentraciones de insulina en un grupo de adolescentes con deficiencia de hormona de crecimiento que recibia tratamiento con la hormona, en un grupo con deficiencia que no recibia tratamiento y en un grupo de control sano. Metodos Se estudio a 22 sujetos con deficit de hormona de crecimiento; 15 recibian hormona de crecimiento (grupo A) y 7 no la recibian (grupo B). La edad del grupo A era de 12xa0±xa02,9 anos, 7 mujeres y 8 varones, 7 prepuberes y el resto puberales; recibieron 0,1xa0U/kg/dia de hormona de crecimiento por un periodo de 3,8xa0±xa01,2 anos. La edad del grupo B era de 13,6xa0±xa01,8, 3 mujeres y 4 varones, 3 prepuberales y el resto puberales que nunca habian recibido hormona de crecimiento. Diecinueve sujetos sanos sin deficiencia de hormona de crecimiento, ajustados por edad osea e indice de masa corporal mas que por edad cronologica participaron como controles (grupo C); 9 mujeres y 10 varones, 11 prepuberes y 8 puberales. Se les tomo el peso y la talla, se calculo el indice de masa corporal y se determinaron las concentraciones basales de leptina e insulina. Resultados No hubo diferencias en las variables antropometricas y en las concentraciones de insulina y leptina entre los grupos. Se detecto un valor significativamente elevado de leptina en las mujeres y en los pacientes puberales, en los grupos A y C. No se encontraron diferencias significativas en el indice de masa corporal segun el sexo, pero si entre sujetos prepuberales y puberales. La elevacion de la leptina en las mujeres fue evidente tanto en el grupo prepuberal como en el puberal, mientras que no se observaron diferencias en relacion con el indice de masa corporal. Las variables independientes que predijeron significativamente la concentracion de leptina fueron el sexo y el indice de masa corporal. Conclusiones a) La concentracion de leptina e insulina no fue diferente en ninos con deficiencia de hormona de crecimiento comparados con ninos sanos, ajustados para el indice de masa corporal; b) se confirma el dimorfismo sexual, caracterizado por concentraciones mas elevadas de leptina en las mujeres, evidente desde la edad prepuberal y que persiste en los estados de deficiencia de hormona de crecimiento, y c) el indice de masa corporal y el sexo fueron las variables independientes predictoras de las concentraciones de leptina.