Ketoacidosis at onset of type 1 diabetes mellitus in pediatric age in Spain and review of the literature.

UNLABELLED: DKA at diagnosis of T1DM is a life-threatening situation that represents the main cause of morbidity and mortality in pediatric patients with T1DM. OBJECTIVE: To determine whether the occurrence and severity of DKA at diagnosis of T1DM has suffered any changes in recent years in the Spanish paediatric population. PATIENTS AND METHODS: Data from 1169 patients with T1DM under 15 years of age was retrospectively studied (2004 -2008) for the presence and severity of DKA at the onset of T1DM, and compared to previous available studies in Spain. This study is multicentric, nationwide with eleven major Paediatric Diabetes Units involved. RESULTS: Complete data were available from 1151 patients (98%). Frequency of DKA was 39.5%, which is not significantly different from previous Spanish studies. 33.8%, children of 0-4.9 years of age, 40.8% aged 5-10.9 and 25.2% aged 11-14.9 years. Mean age of patients with DKA was significantly lower than the one of patients without DKA (7.44 +/- 4.10 versus 8.47 +/- 3.63 years). Mild DKA was occurring more frequently than moderate and severe forms (47.8%, versus 34.4% versus 17.8%, p<0.0001). Incidence of severe DKA was significantly higher in children under 4.9 years of age, especially in those younger than 2 years (p<0.001). Severe DKA led to complications in three children (cerebral oedema [n=1]), cerebral infarction (n=1) and femoral vein thrombosis (n=1). CONCLUSION: Frequency of DKA at diagnosis of T1DM in Spain is still high although most cases were mild. Children under 2 years of age seem to be at increased risk for severe DKA.

Estudio de la variabilidad glucémica en niños y adolescentes con diabetes tipo 1 en tratamiento con insulina glargina / A study of variability in glycaemia in children and adolescents with diabetes mellitus type 1 on treatment with insulin glargine

Objetivo: Determinar la utilidad de la insulina glargina (IG) en la disminución de hipoglucemias e hiperglucemias en niños y adolescentes con diabetes tipo 1. Pacientes y métodos: Se trata de un estudio retrospectivo/prospectivo, en el que 29 pacientes con hipoglucemias leves/moderadas frecuentes, con edades comprendidas entre 3 y 18 años, y HbA1c de 8 ± 0,7, recibieron tratamiento con IG una vez al día e insulina regular o un análogo de la insulina rápida antes de cada comida. Los criterios de inclusión fueron los siguientes: a) tratamiento previo con insulina de acción intermedia (NPH); b) más de 1 año de evolución de la diabetes, y c) más de tres controles de glucemia/día. Se recogió la incidencia de episodios de hipoglucemias (leves, moderadas y graves), hiperglucemias, los valores de HbA1c, el índice de masa corporal y la dosis diaria de insulina antes y después de iniciar el tratamiento con IG. Además, se realiza una encuesta de opinión directa a la familia sobre la calidad de vida. Resultados: Los resultados se obtuvieron a partir de 1.294 ± 411 glucemias/paciente. La incidencia global de hipoglucemias no se reduce (el 5,9 frente al 6,2 % de valores glucémicos/mes) y las hiperglucemias globales permanecen sin cambios. Sin embargo, se reduce de forma significativa la hiperglucemia en ayunas (el 4,3 frente al 2,6 %) con tendencia a la disminución de las hipoglucemias nocturnas. La HbA1c continúa también sin cambios al igual que los requerimientos totales de insulina diaria (0,8 ± 0,2 U/kg/día). Conclusiones: La IG consigue un control glucémico similar al que se logra con la NPH, con tendencia a la disminución de las hipoglucemias nocturnas y a la mejoría de los valores de glucemia en ayunas (AU)

Objective: To determine the usefulness of insulin glargine (IG) to reduce hipoglycaemias and hyperglycaemic events in children and adolescents with type 1 diabetes. Patients and methods: In a retrospective/prospective study, 29 patients with a high number of non-severe hypoglycaemias, aged 3-18, and an average HbA1c of 8 ± 0.7, received IG once daily plus regular insulin or rapid analogue before meals. Inclusion criteria were: a) previous treatment with NPH insulin; b) diagnosis of type 1 diabetes for at least 1 year before starting IG, and c) > 3 blood glucose controls within a day. Incidence of severe and non-severe hypoglycaemic events, hyperglycaemic events, HbA1c values, body mass index, daily insulin dose before and after the institution of glargine therapy, were collected. Additionally, family were asked to complete a diabetes quality of life survey. Results: 1,294 ± 411 glycaemias/subject were obtained. Hypoglycaemic episodes were not reduced (5.9 % vs 6.2 %) and hyperglycaemic events remained unchanged. Fasting blood glucose levels decreased from 195.3 ± 36.6 to 162.8 ± 25.8 in all patients (p < 0.05) and a tendency a decrease in nocturnal hypoglycaemias was observed. The average HbA1c and total daily insulin dosis also remained unchanged (0.8 ± 0.2 UI/Kg/day). Conclusions: Using IG achieves a glycaemic control similar to NPH, with a tendency to decrease the frecuency of nocturnal hypoglycaemias and an improvement in fasting glycaemia values(AU)

[Mosaic trisomy 9: report of a new case with a long-term survival]. / Mosaicismo de trisomía 9: caso de larga supervivencia.

INTRODUCTION: Trisomy 9 is an uncommon chromosome abnormality that may be seen in a mosaic or non-mosaic state. OBJECTIVE: To better define the phenotype and prognosis of this disorder we report a new case of mosaic trisomy 9 with a long-term survival. CLINICAL REPORT: We present the case of a female patient, born from the first pregnancy of a healthy couple. Fetal ultrasounds disclosed intrauterine growth retardation and oligohydramnios. Cesarean section was performed in the 34th week. Birth weight was 1,478 g. Neonatal examination showed: dolichocephaly; hypotelorism, microphthalmia, short palpebral fissures; broad-based nose with bulbous tip; micrognathia; low-set malformed ears; abnormal hands and feet; no other malformations. The initial karyotype determination was normal (46,XX). At 17 months of age, a second karyotype was requested because the patient developed severe psychomotor retardation. Chromosome analysis showed mosaic trisomy 9 (46,XX/47,XX, + 9). Six months later, a single upper central incisor was noted. To our knowledge, this feature has not been reported previously in the trisomy 9. The patient is now 4 years old. She shows severe psychomotor retardation, but no other complications. COMMENTS: It is important to be aware of the possibility that mosaicism may exist in a patient with normal blood karyotype and abnormal phenotype. We conclude that a great number of cells is needed in order to obtain a correct karyotype diagnosis. Correct diagnosis is essential to define the prognosis and provide accurate genetic counselling.

Mosaicismo de trisomía 9: caso de larga supervivencia / Mosaic trisomy 9: report of a new case with a long-term survival

Introducción: La trisomía 9 es una aneuploidía infrecuente y, por tanto, difícil de sospechar. Objetivo: Comunicar un nuevo caso de mosaicismo de trisomía 9, de larga supervivencia, para contribuir al mejor conocimiento de sus características clínicas y pronóstico. Caso clínico: Primera hija de padres sanos. Retraso de crecimiento intrauterino asimétrico y oligohidramnios. Nace a las 34 semanas con 1.478 g de peso, depresión respiratoria y fenotipo anómalo: dolicocefalia; hipotelorismo, microftalmia, hendiduras palpebrales pequeñas; nariz de base ancha y punta en bulbo; micrognatia; orejas de implantación baja, y anomalías en las manos y los pies. Ausencia de malformaciones en los órganos internos. Cariotipo: normal (46,XX). A los 17 meses, ante el retraso psicomotor evidente y las alteraciones descritas se realiza un segundo cariotipo convencional insistiendo en el análisis de un mayor número de células. Se halla un mosaicismo de trisomía 9 (46,XX/47,XX, 1 9). Como dato fenotípico curioso, a los 24 meses aparece un incisivo único superior medial, no descrito antes en otros casos de trisomía 9. Actualmente, tiene 4 años, un retraso mental profundo y ninguna otra complicación. Comentarios: Destaca la mayor dificultad diagnóstica de los mosaicismos; por lo que se debe insistir en el análisis de un número suficiente de células al estudiar el cariotipo. Además, es importante su diagnóstico en sujetos con anomalías fenotípicas, para dar información correcta a los padres en orden a su pronóstico y a la futura descendencia (AU)

Introduction: Trisomy 9 is an uncommon chromosome abnormality that may be seen in a mosaic or non-mosaic state. Objective: To better define the phenotype and prognosis of this disorder we report a new case of mosaic trisomy 9 with a long-term survival. Clinical report: We present the case of a female patient, born from the first pregnancy of a healthy couple. Fetal ultrasounds disclosed intrauterine growth retardation and oligohydramnios. Cesarean section was performed in the 34th week. Birth weight was 1,478 g. Neonatal examination showed: dolichocephaly; hypotelorism, microphthalmia, short palpebral fissures; broad-based nose with bulbous tip; micrognathia; low-set malformed ears; abnormal hands and feet; no other malformations. The initial karyotype determination was normal (46,XX). At 17 months of age, a second karyotype was requested because the patient developed severe psychomotor retardation. Chromosome analysis showed mosaic trisomy 9 (46,XX/47,XX, 1 9). Six months later, a single upper central incisor was noted. To our knowledge, this feature has not been reported previously in the trisomy 9. The patient is now 4 years old. She shows severe psychomotor retardation, but no other complications. Comments: It is important to be aware of the possibility that mosaicism may exist in a patient with normal blood karyotype and abnormal phenotype. We conclude that a great number of cells is needed in order to obtain a correct karyotype diagnosis. Correct diagnosis is essential to define the prognosis and provide accurate genetic counseling (AU)

¿Quiste aracnoideo como causa de pubertad precoz? / Arachnoid cyst as a cause of precocious puberty?

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[A study of variability in glycaemia in children and adolescents with diabetes mellitus type 1 on treatment with insulin glargine]. / Estudio de la variabilidad glucémica en niños y adolescentes con diabetes tipo 1 en tratamiento con insulina glargina.

OBJECTIVE: To determine the usefulness of insulin glargine (IG) to reduce hipoglycaemias and hyperglycaemic events in children and adolescents with type 1 diabetes. PATIENTS AND METHODS: In a retrospective/prospective study, 29 patients with a high number of non-severe hypoglycaemias, aged 3-18, and an average HbA1c of 8+/-0.7, received IG once daily plus regular insulin or rapid analogue before meals. Inclusion criteria were: a) previous treatment with NPH insulin; b) diagnosis of type 1 diabetes for at least 1 year before starting IG, and c) >3 blood glucose controls within a day. Incidence of severe and non-severe hypoglycaemic events, hyperglycaemic events, HbA1c values, body mass index, daily insulin dose before and after the institution of glargine therapy, were collected. Additionally, family were asked to complete a diabetes quality of life survey. RESULTS: 1,294+/-411 glycaemias/subject were obtained. Hypoglycaemic episodes were not reduced (5.9% vs 6.2%) and hyperglycaemic events remained unchanged. Fasting blood glucose levels decreased from 195.3+/-36.6 to 162.8+/-25.8 in all patients (p<0.05) and a tendency a decrease in nocturnal hypoglycaemias was observed. The average HbA1c and total daily insulin doses also remained unchanged (0.8+/-0.2 UI/Kg/day). CONCLUSIONS: Using IG achieves a glycaemic control similar to NPH, with a tendency to decrease the frequency of nocturnal hypoglycaemias and an improvement in fasting glycaemia values.

Bocio endémico en la Comunidad Valenciana / Endemic goiter in the autonomous community of Valencia (Spain)

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[Endemic goiter and iodine deficiency: are they still a reality in Spain]. / Bocio endémico y déficit de yodo: 'sigue siendo una realidad en España?

OBJECTIVE: To estimate the prevalence of goiter and iodine deficiency in a health district in the Autonomous Community of Valencia, given the absence of data in this region of Spain. MATERIAL AND METHODS: We conducted a descriptive, epidemiologic, cross-sectional study, stratified by age and sex, in four interior regions of the province of Valencia. We selected students aged from 6 to 14 years old in 20 centers. Thyroid examination was performed by means of palpation and inspection (goiter > or = 0B). Urinary iodine excretion was analyzed in a routine urine sample. Sociodemographic and anthropometric data, as well as nutritional iodine status, were recorded in a standardized survey. In children with goiter, thyroid-stimulating hormone (TSH), free T4, and antithyroid antibodies were determined. RESULTS: We studied 928 children (478 boys and 450 girls). The prevalence of goiter was 33.7 % (95 % CI: 30.7-36.9 %). There were no significant differences in the prevalence of goiter by age or sex, but an inverse correlation was detected between the prevalence of goiter and parental socioeconomic position. Mean urinary iodine excretion was 155 .g/l, with no significant correlation with the prevalence of goiter. In children with goiter, 13 had positive antithyroid antibodies, 18 had high TSH (subclinical hypothyroidism), and one had suppressed TSH (subclinical hyperthyroidism). CONCLUSIONS: There is endemic goiter in the region studied. Urinary iodine levels were in the normal range and could be interpreted as indicating a transition phase to an improvement in iodine deficiency. Autoimmune diseases would only explain 4 % of cases of goiter.

Bocio endémico y déficit de yodo: ¿sigue siendo una realidad en España? / Endemic goiter and iodine deficiency: are they still a reality in Spain?

Objetivo Determinar la prevalencia de bocio y déficit de yodo en comarcas del interior de la Comunidad Valenciana, dada la ausencia de datos en esta comunidad autónoma. Material y métodos Se trata de un estudio epidemiológico, descriptivo, transversal, estratificado por sexo y edad en cuatro comarcas del interior de la provincia de Valencia. Se estudiaron escolares de 6 a 14 años en 20 centros. La exploración tiroidea se realizó mediante palpación e inspección (bocio ≥ 0B). Se determinó la yoduria en una muestra de orina casual. Se recogieron datos de filiación, antropométricos, y una encuesta sobre el estado nutricional de yodo. En niños con bocio se determinó la hormona tiroestimulante (TSH), la tiroxina libre (T4L) y los anticuerpos antitiroideos. Resultados Se estudiaron 928 niños (478 varones y 450 mujeres). La prevalencia de bocio fue de 33,7 % (IC 95 %: 30,7-36,9). No se hallaron diferencias significativas por edad ni por sexo, aunque sí una correlación inversamente proporcional entre prevalencia de bocio y nivel instrucción paternos. La mediana de yoduria fue 155 μg/l, sin observar una correlación significativa con la prevalencia de bocio. Entre los niños con bocio 13 presentaron los anticuerpos antitiroideos positivos, 18 la TSH elevada (hipotiroidismo subclínico) y uno la TSH suprimida (hipertiroidismo subclínico). Conclusiones Existe una endemia bociosa en las comarcas estudiadas de la Comunidad Valenciana. Los valores de yodurias normales podrían interpretarse como una fase de transición hacia una mejoría del déficit de yodo en esta zona. La patología autoinmune explicaría sólo un 4 % de bocios

Objective To estimate the prevalence of goiter and iodine deficiency in a health district in the Autonomous Community of Valencia, given the absence of data in this region of Spain. Material and methods We conducted a descriptive, epidemiologic, cross-sectional study, stratified by age and sex, in four interior regions of the province of Valencia. We selected students aged from 6 to 14 years old in 20 centers. Thyroid examination was performed by means of palpation and inspection (goiter ≥ 0B). Urinary iodine excretion was analyzed in a routine urine sample. Sociodemographic and anthropometric data, as well as nutritional iodine status, were recorded in a standardized survey. In children with goiter, thyroid-stimulating hormone (TSH), free T4, and antithyroid antibodies were determined. Results We studied 928 children (478 boys and 450 girls). The prevalence of goiter was 33.7 % (95 % CI: 30.7-36.9 %). There were no significant differences in the prevalence of goiter by age or sex, but an inverse correlation was detected between the prevalence of goiter and parental socioeconomic position. Mean urinary iodine excretion was 155 μg/l, with no significant correlation with the prevalence of goiter. In children with goiter, 13 had positive antithyroid antibodies, 18 had high TSH (subclinical hypothyroidism), and one had suppressed TSH (subclinical hyperthyroidism). Conclusions There is endemic goiter in the region studied. Urinary iodine levels were in the normal range and could be interpreted as indicating a transition phase to an improvement in iodine deficiency. Autoimmune diseases would only explain 4 % of cases of goiter

[Effects of valproate on sexual development]. / Efectos del ácido valproico sobre el desarrollo sexual.

INTRODUCTION: Valproate use in young girls has been associated with the adverse endocrinological effects of weight gain and hyperandrogenism. Furthermore, polycystic ovaries and hyperinsulinism have been described in adult women. In men and young boys, however, the possible adverse endocrinological effects of valproate have scarcely been analyzed. OBJECTIVES: The aim of this study was to evaluate the effects of valproate treatment on pubertal development, especially the possible hyperandrogenic effects, in girls and boys with epilepsy. MATERIAL AND METHODS: Twenty-three girls and 15 boys (aged 8-16 years old) who were undergoing valproate treatment for epilepsy were compared with 15 control girls and 10 control boys of the same age range. Anthropometric indexes, sexual maturation, and hirsutism scores were evaluated. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, androstenedione, dehydroepiandrosterone, estradiol, and insulin were measured. Ultrasound examination of ovaries and estimation of bone age through X-ray of the left hand were also performed. RESULTS: Valproate did not affect pubertal development in the study group. No hirsutism or polycystic ovaries were found. Increases in weight, relative weight, and body mass index were observed in the group undergoing valproate treatment, but no statistically significant differences compared with the control group were found. Plasma testosterone was higher in valproate-treated girls (0.71 0.51 ng/ml) than in control girls (0.35 0.15) (p 0.001). This finding was independent of valproate dose and treatment duration. Hyperandrogenism was not found in valproate-treated boys. CONCLUSIONS: Valproate may induce hyperandrogenism in epileptic girls but not in boys. This is an early adverse effect and is independent of the dose used. No changes in normal pubertal development or physical repercussions were found in epileptic patients.

Efectos del ácido valproico sobre el desarrollo sexual / Effects ofvalproate on sexual development

Introducción La utilización del ácido valproico se ha relacionado en niñas y adolescentes con efectos adversos endocrinológicos: ganancia de peso e hiperandrogenismo. Además, en mujeres adultas se han descrito ovarios poliquísticos e hiperinsulinismo. En varones apenas se han estudiado los posibles efectos adversos endocrinológicos. Objetivos: El objetivo de este estudio fue evaluar los efectos del ácido valproico en el desarrollo puberal en chicas y en chicos epilépticos, en especial relación con su posible efecto hiperandrogénico. Material y métodos: Se incluyeron 23 chicas y 15 chicos (entre 8 y 16 años) epilépticos, tratados con ácido valproico, se compararon con 15 niñas control y 10 niños control del mismo rango de edad. Se valoraron índices antropométricos y las escalas de desarrollo sexual e hiperandrogenismo. Se midieron las concentraciones séricas de hormona foliculostimulante (FSH) y luteinizante (LH), testosterona, androstendiona, deshidroepiandrosterona, estradiol e insulina. Se valoraron los ovarios mediante ecografía y la edad ósea mediante radiografía de la mano izquierda. Resultados: El ácido valproico no afectó el desarrollo puberal en el grupo estudio. No se apreció hirsutismo ni ovarios poliquísticos. Se observó un aumento de peso, peso relativo e índice de masa corporal, pero sin que existieran diferencias estadísticamente significativas respecto al grupo control. La testosterona plasmática en las niñas tratadas (0,71 0,51 ng/ml) fue mayor que en el grupo control (0,35 0,15) (p 0,001) y este hallazgo fue independiente del tiempo de tratamiento o de la dosis empleada. En los chicos tratados no se encontró hiperandrogenismo. Conclusiones: El ácido valproico induce hiperandrogenismo analítico en niñas epilépticas, pero no en niños. Este es un efecto adverso precoz e independiente de la dosis. No hay cambios en el desarrollo puberal normal ni repercusión clínica en los/as pacientes epilépticos/as (AU)

[Renal function in diabetic children and adolescents. Relation to the duration and level of control of the disease]. / Función renal en niños y adolescentes diabéticos. Relación con la duración y nivel de control de la enfermedad.

We have evaluated different aspects of the kidney function of 68 diabetic children and adolescents with the aim of estimating the prevalence of nephropathy and its influential factors. In addition, the kidney function is followed for an additional 18 months. The results are compared with those obtained from a group of healthy children of the same ages. No clinical nephropathy existed, with only 4 (5.97%) and 8 cases of incipient nephropathy and microalbuminuria, respectively, being demonstrated. The urinary albumin excretion rate (AER) is very clearly connected with the duration and the metabolic control of diabetes. Elevated values for AER were also observed in poorly controlled diabetics and those with prolonged evolution. Nevertheless, the last point may be secondary to the development of puberty, since with the same duration of diabetes (under 5 years), the proportion of pubertal patients with microalbuminuria is higher than that for prepubertal children.

[Theophylline toxicity in infants]. / Toxicidad de la teofilina en el lactante.

In order to evaluate risk factors and clinical manifestations of theophylline intoxication in the infant, a comparative study between intoxicated and non intoxicated during a period of 4 years has been made. The incidence of this complication was 9.5% (7/74). Except for the cases of 2 children where there was an administrative error, everyone received a similar dose, finding great variability in the reaction to the drug. Only age seems to contribute to an increased tendency to intoxication (6/7 less than or equal to 3 months). Concerning the clinical manifestations, we do not find any correlation between the theophylline levels and severity. All the infants presented tachicardia and irritability, 3/4 tonic-clonic seizures and/or episodes and 1/7 severe metabolic disturbances. Only 1/7 had prodromic symptoms, therefore in view of the variability in individual tolerance, we believe that theophylline should not be used for small without an appropriate control of its serum concentrations.

[Psychological evaluation of diabetic students and their families]. / Valoración psicológica del escolar diabético y su familia.

A population of 29 diabetic school children has been studied with the purpose of evaluating the repercussion the disease has on the psychosocial development of the child. Eysenck's inventory of personality, Achembach's IPCDS and the drawing of the human figure have been employed as psychological test. The sociological aspects are valued through interviewing and questionnaires. The outstanding conclusions are: 1. Diabetes does not condition the development of a specific personality. 2. Psychiatric alterations and pathological behaviours are not present in the diabetic school child with a greater frequency than in the normal child. The most problematic is the pattern of behaviour found in preadolescent teenagers, individual cases stand out in relation to their antisocial and reserved behaviour. 3. The disease neither cuts down social life, nor does it condition the appearance of school-failure, but it does have a repercussion and a modifying effect on practical aspects of family life and the relations among its members.

[Limitation in articular movement in diabetic children]. / Limitación de la movilidad articular en niños diabéticos.

The presence of limited movement articular (LMA) was examined in 58 insulin-dependent diabetic children 38 boys and 20 girls in a range of 1 to 18 years. The children were ill during a mean of 4 years and 7 months +/- 3 years and nine months. The MAL was present in 36.2% of diabetic children versus 2.08% in the control group (96 healthy children). The presence of MAL has a statistically significant correlation with: age (9 years or more) (p less than 0.01); poor metabolic control (specially in severe forms) (p less than 0.001) and retinopathy (p less than 0.02). The examination of LMA is very useful for the early diagnosis of retinopathy in high risk patients because of the very frequent association of both complications of diabetes.