The effect of short- and long-term growth hormone treatment on bone mineral density and bone metabolism of prepubertal children with idiopathic short stature: a 3-year study.

OBJECTIVE: We recently reported that children with idiopathic short stature (ISS) have decreased lumbar spine bone mineral density (BMD) that increases after 1 year of GH therapy. The aim of this study was to confirm these short-term results and to evaluate the effect of long-term GH therapy on the BMD of children with ISS. PATIENTS AND DESIGN: We treated a group of 16 short, slow-growing but otherwise healthy non-GH-deficient prepubertal children (8 girls and 8 boys) with a chronological age of 9.5 +/- 0.9 years, a bone age of 8.1 +/- 1.2 years and a height of 124.3 +/- 6.3 cm (height-SDS of -2.1 +/- 0.6) with GH at a dose of 0.1 IU/kg/day for 3 consecutive years. MEASUREMENTS: Height was determined at 3-month intervals and annual growth velocities were calculated. Bone ages and BMD were measured every 12 months by dual-energy X-ray absorptiometry, as were serum concentrations of the carboxy-terminal propeptide of type 1 collagen (PICP) and the carboxy-terminal cross-linked telopeptide of type 1 collagen (ICPT). RESULTS: Growth velocity increased from 4.0 +/- 0.8 cm/year to 8.7 +/- 1.5 and 8.0 +/- 1.7 cm/year at 12 and 36 months of GH therapy, respectively, while height-SDS improved from -2.1 +/- 0.6 to -1.6 +/- 0.4 after 36 months of GH (P < 0.0001). Baseline lumbar spine BMD was decreased when compared to that of a control group of healthy children paired for gender, bone age and height (0.640 +/- 0.08 g/cm2vs. 0.730 +/- 0.08 g/cm2; P < 0.003). Lumbar spine BMD increased after 1 year of GH from 0.640 +/- 0.08 to 0.749 +/- 0.08 g/cm2 (P < 0.05), reaching levels similar to that of controls followed for 1 year without therapy (0.749 +/- 0.04 g/cm2vs. 0.760 +/- 0.08 g/cm2). During this period lumbar spine BMD increased 14.5% in the ISS subjects and 3.9% in the controls. Over the following 2 years of GH therapy the lumbar spine BMD of our ISS patients increased at a rate similar to that of the control population, so that after 3 years of consecutive GH therapy the lumbar spine BMD of ISS children was comparable to that of the controls (0.784 +/- 0.12 g/cm2vs. 0.785 +/- 0.09 g/cm2). Femoral neck BMD of our patients was similar to that of the controls at baseline and at 36 months. Following 1 year of GH treatment serum concentrations of PICP increased from 229.6 +/- 63.5 to 358.6 +/- 87.9 micro g/l, while levels of ICTP increased from 9.6 +/- 5.9 to 13.7 +/- 2.1 micro g/l. After 36 months of GH therapy, PICP and ICTP values had decreased to 303.3 +/- 67.2 micro g/l and 11.3 +/- 3.3 micro g/l, respectively, and were no longer significantly different from baseline. CONCLUSIONS: Children with ISS have decreased lumbar spine BMD, which normalized after 1 year of GH. Over the next 2 years of therapy lumbar spine BMD increased at a normal rate, so that after 3 consecutive years of GH the lumbar spine BMD of children with ISS was similar to that of controls. Bone turnover increased with treatment as indicated by a rise in bone formation and bone resorption markers.

Cardiac mass and function, carotid artery intima-media thickness and lipoprotein (a) levels in children and adolescents with type 1 diabetes mellitus of short duration.

OBJECTIVE: To evaluate cardiac mass and function, carotid intima-media thickness, and serum lipid and lipoprotein (a) (Lpa) levels in children and adolescents with type 1 diabetes mellitus (DM) of short duration. BACKGROUND: Diabetes mellitus has been found to be an important risk factor for macrovascular disease in adults. Increased serum lipids and Lpa levels have been reported in adolescents with type 1 DM; atherosclerotic vascular lesions involving a combination of fatty degeneration and vessel stiffening of the arterial wall and myocardial involvement impairing diastolic function may be present in adolescents and young adults with type 1 DM. DESIGN/METHODS: Twenty children and adolescents (10 males, 10 females) diagnosed with type 1 DM before 3.4 +/- 3.3 years with a mean age of 11.9 +/- 3.6 years were studied; their HbA1c levels were 8.0 +/- 1.9%. Twenty healthy non-diabetic controls, 10 males and 10 females, aged 12.1 +/- 3.4 years, matched for height and weight, participated in the study. Fasting blood samples were obtained for lipid and Lpa analysis. Patients underwent transthoracic M-mode and two-dimensional echocardiographic evaluation for measurement of left atrial and ventricular dimensions and left ventricular (LV) wall thickness and mass. Stroke volume and cardiac output were measured using pulsed Doppler echocardiography; carotid intima-media thickness was measured using high-resolution mode B ultrasound. RESULTS: Interventricular septal thickness (7.1 +/- 1.8 vs 7.0 +/- 1.5 mm), LV posterior wall thickness (7.1 +/- 1.4 vs 7.5 +/- 2.0 mm) and LV mass after correction for body surface area (70.6 +/- 27.4 vs 70.7 +/- 18.0 g/m2) were similar in patients and controls. Similarly, the LV ejection fraction at rest was similar in patients and controls (69.9 +/- 2.3 vs 70.0 +/- 0.6%), as were pulmonary venous flow velocities (0.56 +/- 0.09 vs 0.55 +/- 0.10 m/s for diastolic peak velocity, 0.54 +/- 0.08 vs 0.50 +/- 0.09 m/s for systolic peak velocity and 0.17 +/- 0.07 vs 0.19 +/- 0.05 m/s for atrial reversal filling). Carotid intima-media thickness (0.60 +/- 0.02 and 0.59 +/- 0.02 mm for the right and left carotid artery) was similar to that of controls (0.60 +/- 0.03 and 0.61 +/- 0.02 mm for the right and left carotid artery). Low density lipoprotein cholesterol and Lpa levels were increased in patients compared to controls (113.2 +/- 26.0 mg/dl and 20.1 +/- 11.7 mg/dl in patients vs 90.4 +/- 14.3 mg/dl and 9.8 +/- 2.9 mg/dl in controls; p <0.01), while total cholesterol, HDL cholesterol and serum triglyceride concentrations were similar to those in controls. CONCLUSIONS: Although children and adolescents with type 1 DM seem not to show alterations in cardiac mass and function or early atherosclerotic changes in the first few years after diagnosis, their cardiovascular risk is increased as they present with dyslipidemia at an early stage of the disease.

El control glicemico en la velocidad de crecimiento y en diversos aspectos metabolicos en niños con diabetes mellitus insulino-dependiente tratados en forma convencional / The glycemic control on the growth velocity and several metabolic aspects of children with insuline dependient diabetes melltitus children were treatise in conventional form

Para determinar el efecto que tiene el control glicémico en la velocidad de crecimiento y diversos parámetros metabólicos en niños con diabetes mellitus insulino dependiente (DMID), 79 niños con DMID, 45 hembras y 34 varones con una edad promedio de 8.4 ñ 3.0 años fueron seguidos durante cinco años desde el momento del inicio de la enfermedad. El control glicémico fué realizado midiendo la hemoglobina glicosilitada (GHb) total; los niños fueron divididos en mal control metabólico (Grupo B), GHb>9 por ciento, 49 pacientes y buen control metabólico (Grupo A) GHb<9 por ciento, 30 niños. La velocidad de crecimiento fue significativamente menor durante los cinco años de seguimiento en el grupo B comparado con el grupo A (4,8 ñ 1.6 vs. 6.7 ñ 2.2 cm/años después del primer año y 5.0 ñ 2.0 vs. 6.5 ñ 1.8 cm/años al final del quinto año, en el grupo B y A, respectivamente). Presentaron niveles mayores de colesterol (185.3 ñ 33.7 vs. 158.8 ñ 39.5 mg/dl) y triglicéridos (85.9 ñ 43.5 vs. 71.0 ñ 37.4 mg/dl) el grupo B, al compararlos con el grupo A. La dosis de insulina diaria no fué significativamente en los dos grupos (0.76 ñ 0.3 vs. 0.84 ñ 0.4 U/Kg/día en el primer año y 0.9 ñ 0.3 vs. 0.92 ñ 0.4 U/Kg/día en el quinto año, en el grupo B y A respectivamente). A pesar de que ambos grupos recibieron el mismo entrenamiento inicial diabético por un equipo multidisciplinario, al igual que el mismo número inicial de inyecciones de insulina, se observó un monitoreo más frecuente de las glicemias capilares, mejores anotaciones de las mismas y mejor rotación en los sitios de inyección y con visitas más regulares a la consulta externa en el grupo A. Los episodios de ceto-acidosis diabética fueron más frecuentes en el grupo B, mientras que el grupo A presentó un mayor números de episodios hipoglicémicos. En conclusión, hemos encontrado que el mal control glicémico reflejado por niveles elevados de GHb afectan la velocidad de crecimiento y diversos parámetros metabólicos de niños con diabetes mellitus Tipo I durante los primeros cinco años de la enfermedad. Existen otros factores a parte de la dosis de insulina y del entrenamiento inicial y sucesivo de la diabetes, que juegan un papel importante en el control glicémico de estos pacientes.