Síndrome de insulinorresistencia severa tipo A debido a mutación del gen del receptor de insulina / Severe type A insulin resistance syndrome due to a mutation in the insulin receptor gene

Los síndromes monogénicos de insulinorresistencia sin lipodistrofia constituyen un rupo de entidades infrecuentes que incluyen los síndromes de Donohue o leprechaunismo, Rabson-Mendenhall y resistencia a la insulina tipo A. Se caracterizan por un amplio espectro fenotípico que asocia insulinorresistencia extrema y alteraciones hidrocarbonadas de grado variable. Presentamos un caso de resistencia a la insulina tipo A, caracterizado por resistencia insulínica grave, acantosis nigricans e hiperandrogenismo, debido a una mutación en heterocigosis en el xón 19 del gen del receptor de insulina que codifica para el dominio tirosinquinasa. Se destaca la elevada morbilidad de dicha entidad, a pesar de incluirse dentro del espectro menos grave de los síndromes genéticos de resistencia insulínica, así como la ausencia de una terapia satisfactoria. El estudio molecular revela el diagnóstico e informa del pronóstico y la supervivencia, factores ligados a la función residual del receptor, además de contribuir al desarrollo de nuevas dianas terapéuticas

Insulin resistance syndromes without lipodystrophy are an infrequent and heterogeneous group of disorders with variable clinical phenotypes, associated with hyperglycemia and hyperinsulinemia. The three conditions related to mutations in the insulin receptor gene are leprechaunism or Donohue syndrome, Rabson-Mendenhall syndrome, and Type A syndrome. A case is presented on a patient diagnosed with type A insulin resistance, defined by the triad of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism, carrying a heterozygous mutation in exon 19 of the insulin receptor gene coding for its tyrosine kinase domain that is crucial for the catalytic activity of the receptor. The molecular basis of the syndrome is reviewed, focusing on the structure-function relationships of the insulin receptor, knowing that the criteria for survival are linked to residual insulin receptor function. It is also pointed out that, although type A insulin resistance appears to represent a somewhat less severe condition, these patients have a high morbidity and their treatment is still unsatisfactory

[Severe type A insulin resistance syndrome due to a mutation in the insulin receptor gene]. / Síndrome de insulinorresistencia severa tipo A debido a mutación del gen del receptor de insulina.

Insulin resistance syndromes without lipodystrophy are an infrequent and heterogeneous group of disorders with variable clinical phenotypes, associated with hyperglycemia and hyperinsulinemia. The three conditions related to mutations in the insulin receptor gene are leprechaunism or Donohue syndrome, Rabson-Mendenhall syndrome, and Type A syndrome. A case is presented on a patient diagnosed with type A insulin resistance, defined by the triad of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism, carrying a heterozygous mutation in exon 19 of the insulin receptor gene coding for its tyrosine kinase domain that is crucial for the catalytic activity of the receptor. The molecular basis of the syndrome is reviewed, focusing on the structure-function relationships of the insulin receptor, knowing that the criteria for survival are linked to residual insulin receptor function. It is also pointed out that, although type A insulin resistance appears to represent a somewhat less severe condition, these patients have a high morbidity and their treatment is still unsatisfactory.

Utilidad del tratamiento con infusión subcutánea continua de insulina en la edad pediátrica / Utility of treatment with continuous subcutaneous insulin infusion in the pediatric age

La terapia con infusión subcutánea de insulina se utiliza desde hace más de 30 años aunque no ha sido hasta la última década cuando ha aumentado su utilización de forma notable. El desarrollo de dispositivos de infusión más modernos, seguros y fáciles de utilizar, así como la posibilidad de asociar sistemas de monitorización continua de la glucosa está cambiando el paradigma del tratamiento de la diabetes en la edad pediátrica. Diversos estudios han demostrado que el tratamiento con ISCI es una alternativa eficaz y segura. El propósito de este artículo es revisar los principales beneficios y riesgos asociados a la terapia con bomba de insulina (AU)

Therapy with continuous subcutaneous insulin infusion (CSII) has been used for the last thirty years although it has not been until the last decade when its use has increased notably. The development of the insulin infusion devices that are smaller, safer and more user friendly, as well as the possibility to utilize them in combination with the continuous glucose monitoring systems are changing the paradigm of the pediatric diabetes care. Several studies have shown that CSII is a safe and effective alternative for the treatment of children and adolescents with type 1 diabetes mellitus. In this article the major benefits and risks associated with insulin pump therapy are reviewed (AU)

[Continuous glucose monitoring system in the screening of glucose disorders in cystic fibrosis]. / Monitorización continua de glucosa para cribado de alteraciones hidrocarbonadas en fibrosis quística.

BACKGROUND: Diabetes mellitus (DM) is an increasing complication of cystic fibrosis (CF). It is associated with enhance morbidity. Continuous glucose monitoring system (CGMS) could detect glucose disorders earlier than other screening tests usually used. AIMS: To compare oral glucose tolerance test (OGTT), HbA(1c) and CGMS in patients with CF and recent disorders of glucose homeostasis and to analyse changes in nutritional status and/or pulmonary function. PATIENTS AND METHODS: Thirteen patients with CF (11-22 years, 7 males) were studied using OGTT, HbA(1c) and CGMS. All of them had newly diagnosed glucose disturbances. They were not receiving steroid therapy or had an underlying illness. In all subjects we compared: HbA(1c) levels (%), fasting and 2-hours glucose OGTT (mg/dl) and glucose CGMS values (overall, fasting, 2-hours post mean-meals and excursions >140mg/dl at any time). Furthermore, body mass index, forced expiratory volume in the first second (%) and forced vital capacity (%) were evaluated in the previous year and at the time of the study. We also analysed exocrine pancreatic function and CF-mutation. RESULTS: Mean age at diagnosis of glucose disturbance was 16.4 years. All patients had insufficient exocrine pancreatic function and 11/13 presented DeltaF508 CF-mutation. Only one patient was diagnosed with DM using OGGT and 7/13 (53.8%) with CGMS. A total 77% of patients had poor nutritional status and/or pulmonary function at time of diagnosing the glucose disorder. Only 4 patients had abnormal HbA(1c) levels. CONCLUSIONS: CGMS allows a better detection of glucose disorders than OGTT. Glucose homeostasis abnormalities are associated with a decrease in nutritional status and/or pulmonary function. HbA(1c) does not aid in the early diagnose of glucose disorders.

Monitorización continua de glucosa para cribado de alteraciones hidrocarbonadas en fibrosis quística / Continuous glucose monitoring system in the screening of glucose disorders in cystic fibrosis

Introducción: las alteraciones hidrocarbonadas (AHC) en fibrosis quística (FQ) suelen ser asintomáticas pero conllevan gran morbilidad. Su diagnóstico precoz puede prevenir el deterioro del estado nutricional y de la función pulmonar (FP). Objetivos: comparar los resultados de la monitorización continua de glucosa (CGMS) con los de la sobrecarga oral de glucosa (SOG) en pacientes con FQ. Evaluar la utilidad de la hemoglobina glicosilada (HbA1c) para el diagnóstico precoz de AHC. Analizar los cambios del estado nutritivo y función pulmonar al diagnóstico de AHC. Pacientes y métodos: en 13 pacientes púberes (7 varones) con FQ y AHC, diagnosticada por SOG, implantamos CGMS. Analizamos: edad, sexo, mutación relacionada con FQ, insuficiencia pancreática exocrina, HbA1c (%), glucemia en ayunas y 2h tras SOG. En el CGMS valoramos: glucosa global, en ayunas y posprandial, y excursiones de glucosa >140mg/dl. Además, comparamos el estado nutricional (índice de masa corporal) y la FP (capacidad vital forzada y volumen espiratorio forzado en el primer segundo) en ese momento y en el año previo. Resultados: media de edad al diagnóstico de AHC de 16,4 años (11-22); 11 pacientes tenían mutación ΔF508. Todos tenían insuficiencia pancreática exocrina. Cumplían criterios de diabetes 1/13 con SOG y 7/13 (53,8%) con CGMS. Se evidenció una declinación del estado nutricional y/o de la FP en el 77%. Sólo 4 pacientes tenían HbA1c patológica. Conclusiones: el CGMS detecta mejor la diabetes relacionada con FQ que la SOG. La presencia de AHC tiende a relacionarse con un empeoramiento nutricional y/o de FP. La HbA1c no permite el diagnóstico precoz de AHC en FQ (AU)

Background: Diabetes mellitus (DM) is an increasing complication of cystic fibrosis (CF). It is associated with enhance morbidity. Continuous glucose monitoring system (CGMS) could detect glucose disorders earlier than other screening tests usually used. Aims: To compare oral glucose tolerance test (OGTT), HbA1c and CGMS in patients with CF and recent disorders of glucose homeostasis and to analyse changes in nutritional status and/or pulmonary function. Patients and methods: Thirteen patients with CF (11–22 years, 7 males) were studied using OGTT, HbA1c and CGMS. All of them had newly diagnosed glucose disturbances. They were not receiving steroid therapy or had an underlying illness. In all subjects we compared: HbA1c levels (%), fasting and 2-hours glucose OGTT (mg/dl) and glucose CGMS values (overall, fasting, 2-hours post mean-meals and excursions >140mg/dl at any time). Furthermore, body mass index, forced expiratory volume in the first second (%) and forced vital capacity (%) were evaluated in the previous year and at the time of the study. We also analysed exocrine pancreatic function and CF-mutation. Results: Mean age at diagnosis of glucose disturbance was 16.4 years. All patients had insufficient exocrine pancreatic function and 11/13 presented ΔF508 CF-mutation. Only one patient was diagnosed with DM using OGGT and 7/13 (53.8%) with CGMS. A total 77% of patients had poor nutritional status and/or pulmonary function at time of diagnosing the glucose disorder. Only 4 patients had abnormal HbA1c levels. Conclusions: CGMS allows a better detection of glucose disorders than OGTT. Glucose homeostasis abnormalities are associated with a decrease in nutritional status and/or pulmonary function. HbA1c does not aid in the early diagnose of glucose disorders (AU)

Tratamiento con infusión subcutánea continua de insulina en pacientes pediátricos con diabetes mellitus tipo 1. Respuesta de los autores / Treatment with continuous subcutaneous insulin infusion in pediatric patients with type 1 diabetes mellitus. Author’s response

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[Continuous subcutaneous insulin infusion in pediatric patients with type 1 diabetes mellitus]. / Tratamiento con infusión subcutánea continua de insulina en pacientes pediátricos con diabetes mellitus tipo 1.

INTRODUCTION: To determine the efficacy and safety of continuous subcutaneous insulin infusion therapy in a group of children and adolescents with type 1 diabetes mellitus. PATIENTS AND METHODS: Data from 17 patients were collected during the first year of continuous subcutaneous insulin infusion treatment. All patients were followed-up at our diabetic pediatric clinic. HbA1c, body mass index, insulin dose, severe hypoglycemic episodes, and diabetic ketoacidosis events before and after initiation of pump therapy were compared. RESULTS: The mean age was 14.02 +/- 3.70 years and the mean diabetes duration was 5.81 +/- 3.31 years. HbA1c decreased from 8.12 +/- 1.46 to 7.52 +/- 0.87 % after 2 months of therapy and this decrease was maintained throughout the first year of continuous subcutaneous insulin infusion treatment. Insulin dose decreased from 0.99 +/- 0.24 to 0.84 +/- 0.18 U/kg/day after 1 year of treatment. Body mass index remained unchanged. There were fewer severe hypoglycemic events after the start of insulin pump therapy (0.47 +/- 1.23 events/patient in the 6 months before continuous insulin infusion, 0.29 +/- 1.20 episodes in the first 6 months of insulin pump therapy and 0.06 +/- 0.24 in the period from 6 to 12 months of the treatment). There were 3 ketoacidosis episodes, all in the same patient. CONCLUSIONS: Continuous subcutaneous insulin infusion is a safe and effective alternative in the treatment of children and adolescents with type 1 diabetes mellitus. It improves metabolic control and decreases the number of severe hypoglycemic episodes.

Tratamiento con infusión subcutánea continua de insulina en pacientes pediátricos con diabetes mellitus tipo 1 / Continuous subcutaneous insulin infusion in pediatric patients with type 1 diabetes mellitus

Introducción El propósito del estudio es determinar la eficacia y la seguridad del tratamiento con bombas de infusión subcutánea continua de insulina en un grupo de niños y adolescentes con diabetes mellitus tipo 1. Pacientes y métodos Se analizan los datos de 17 pacientes diabéticos tratados en nuestra Unidad de Diabetes Pediátrica durante el primer año de terapia con bomba de infusión subcutánea continua de insulina. Comparamos la HbA1c, índice de masa corporal, dosis de insulina, episodios de hipoglucemia grave y episodios de cetoacidosis antes y después del inicio de la terapia con bomba de insulina. Resultados La media de edad fue de 14,02 ± 3,70 años y el tiempo medio de evolución de la diabetes de 5,81 ± 3,31 años. Se objetiva una disminución de HbA1c de 8,12 ± 1,46 a 7,52 ± 0,87 % a los 2 meses de tratamiento que se mantiene en estas concentraciones durante todo el año. La dosis de insulina disminuye de 0,99 ± 0,24 a 0,84 ± 0,18 U/kg/día al año de tratamiento. El índice de masa corporal permanece estable. También se observa una disminución del número de episodios de hipoglucemia grave (0,47 ± 1,23 episodios/paciente en los 6 meses previos al inicio del tratamiento con bomba, 0,29 ± 1,20 durante los primeros 6 meses de la nueva terapia y 0,06 ± 0,24 de los 6 a 12 meses). Hubo tres episodios de cetoacidosis, todos ellos en el mismo paciente. Conclusiones La terapia con bomba de infusión subcutánea continua de insulina es una alternativa eficaz y segura para tratar niños y adolescentes con diabetes mellitus tipo 1, ya que permite mejorar el control metabólico con disminución del riesgo de hipoglucemia grave

Introduction To determine the efficacy and safety of continuous subcutaneous insulin infusion therapy in a group of children and adolescents with type 1 diabetes mellitus. Patients and methods Data from 17 patients were collected during the first year of continuous subcutaneous insulin infusion treatment. All patients were followed-up at our diabetic pediatric clinic. HbA1c, body mass index, insulin dose, severe hypoglycemic episodes, and diabetic ketoacidosis events before and after initiation of pump therapy were compared. Results The mean age was 14.02 ± 3.70 years and the mean diabetes duration was 5.81 ± 3.31 years. HbA1c decreased from 8.12 ± 1.46 to 7.52 ± 0.87 % after 2 months of therapy and this decrease was maintained throughout the first year of continuous subcutaneous insulin infusion treatment. Insulin dose decreased from 0.99 ± 0.24 to 0.84 ± 0.18 U/kg/day after 1 year of treatment. Body mass index remained unchanged. There were fewer severe hypoglycemic events after the start of insulin pump therapy (0.47 ± 1.23 events/patient in the 6 months before continuous insulin infusion, 0.29 ± 1.20 episodes in the first 6 months of insulin pump therapy and 0.06 ± 0.24 in the period from 6 to 12 months of the treatment). There were 3 ketoacidosis episodes, all in the same patient. Conclusions Continuous subcutaneous insulin infusion is a safe and effective alternative in the treatment of children and adolescents with type 1 diabetes mellitus. It improves metabolic control and decreases the number of severe hypoglycemic episodes

[Graves' disease in preschool children]. / Enfermedad de Graves-Basedow en el niño preescolar.

Graves' disease, which is the main cause of hyperthyroidism in the pediatric age group, is very rare in pre-school children. We describe the cases of four girls, aged less than 6 years old, out of a total of 30 patients diagnosed with Graves' disease between 1985 and 2004. Investigations were motivated by tachycardia, chronic diarrhea, language development delay or thyroid nodules detected by cervical ultrasonography. In three of the four patients height and bone age were advanced. In all patients goiter was small or absent. None of the patients had ophthalmic disease. In all patients free T3 and T4 were elevated and thyroid-stimulating hormone was suppressed. Three patients were positive for thyroid-stimulating immunoglobulins (the method was not available for the oldest case). Two patients showed complete resolution after 5 years of treatment with carbimazole. The remaining two patients are still under treatment and no adverse effects have been documented.