Polimorfismo -174 G/C del gen promotor de interleuquina 6 en mujeres con diabetes mellitus tipo 1 / -174 G/C polymorphism of interleukin 6 gene in women with type 1 diabetes

Background: A polymorphism located in the promoter region (-174 G I C) of interleukin 6 (IL-6) has been linked to early onset of type 1 diabetes (T1D) and increased body mass index (BMI). Aim: To evaluate the possible association of this -IL-6 gene 174 GIC polymorphism with T1D, BMI and metabolic control in T1D patients in a case-control study. Patients and Methods:-174 G I C polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism in 145 women with T1D and 103 healthy controls. BMI and BMI-Z-scores were tabulated and metabolic control was recorded. Results: There was a higher frequency for the C allele in T1D patients compared with the control group (21 percent versus 14.1 percent, p = 0.047). No significant differences in genotype frequencies for the -174 GIC polymorphism of IL-6 gene between patients with T1D and controls, were observed. There were no significant associations with T1D and BMI. Conclusions: A higher frequency of C allele in women with T1D was the only finding in this series, suggesting that the polymorphic variant is not related to weight gain in these patients.

Diabetes mellitus tipo 2 e intolerancia a la glucosa en niños y adolescentes con obesidad: ¿una epidemia moderna? / Frequency of diabetes mellitus and glucose intolerance among obese children and adolescents

Background: The prevalence obesity, type 2 diabetes (DM2) and glucose intolerance among children is increasing worldwide. Aim: To assess the frequency of DM2 and GI among severely obese children and adolescents. Patients and methods: Cross sectional study of 69 children and adolescents aged 12 +/- 3 years with a mean body mass index (BMI) z score of 2.9 +/- 0.6. An oral glucose tolerance test (OGTT) was performed, measuring fasting and 120 minutes blood glucose and insulin. According to these results two patients had diabetes mellitus and 4 had glucose intolerance. Previously studied patients, five with diabetes mellitus and two with glucose intolerance were incorporated to the present study. These 13 participants were compared with the remaining 63 children without abnormalities in glucose metabolism, considered as controls. Results: Body mass index among children with glucose intolerance, diabetes mellitus and controls was 33.8 +/- 6.4, 26.7 +/- 5.1 and 29.4 +/- 4.5 kg/m2, respectively, p = 0.03. Basal and 120 min insulin levels were also significantly higher among children with glucose intolerance compared with diabetics and controls. Homeostasis model assessment for insulin resistance was significantly lower in controls than in children with diabetes or glucose intolerance. Conclusions: Eight percent of this group of obese children and adolescents had DM2 or glucose intolerance. Oral glucose tolerance test should be included in the routine assessment of obese children to diagnose abnormalities of glucose metabolism.

Relación entre el polimorfismo -34 Bp de la región promotora del gen CYP17 con el perfil hormonal y metabólico en mujeres con diabetes mellitus tipo 1 / Relationship of -34 Bp polymorphism in the promoter of Cyp17 gene with hormonal and metabolic profile in women with type 1 diabetes mellitus

The P450c17a enzyme has a central role in ovarian hyperandrogenism, which is a characteristic of polycystic ovary syndrome (PCOS). Several studies have suggested a possible role for the CYP17 gene, which codes for the enzyme P450c17a and the -34bp T-C polymorphism in the development of hyperandrogenism. The presence of the cytosine, know as A2 allele, has been associated with hyperandrogenism in patients with PCOS. Objective: To evaluate the frequency and association of the -34bp polymorphism in the CYP17 gene and determine its association with hormonal and metabolic characteristics in women with DM1. Patients and Methods: The CYP17 polymorphism was studied in 72 DM1 and 71 control women by PCR and RFLP analysis. The CYP17 genetic dosage was compared with the antropometrical characteristics and the serum concentrations of testosterone, androstenedione, DHEAS and 17OH progesterone in women with DM1. Results: Genotype A2/A2 was present in 20.8 percent and 7.1 percent of DM1 and controls, respectively (p = 0,034). Allele A2 was present in 40.3 percent and 27.5 percent of DM1 and healthy women, respectively (p = 0,031). No association between CYP17 genotypes and hormonal or metabolic characteristics was observed. Conclusion: This study shows that the frequency of the A2/A2 genotype was higher in women with DM1 than in the control group. However, no association between the presence of the polymorphism and circulating steroid levels or BMI was observed.

Evaluación de un programa integral de tratamiento de obesidad y sobrepeso en niños escolares y adolescentes en Santiago de Chile (1999-2006) / Assessment of a multidisciplinary program for the treatment of obesity in children

Background: Medical treatment of obesity requires a multidisciplinary approach including dietary, exercise and behavioral interventions. Aim: To report the results of a multidisciplinary program for the treatment of obesity in children. Patients and Methods: Three hundred twenty four children (155 males), aged between 5 and 18 year, were treated with diet, exercise and behavioral modification, between 1999 and 2006. At baseline and at the end of follow up, weight, height, z score for body mass index (BMI), blood pressure and features of the metabolic syndrome were assessed. Results: z scores for IMC decreased by 0.28 points (95 percent confidence intervals: -0.31 to -0.25). Sixty percent of patients achieved a weight reduction of 5 percent of more of their initial weight. In a multiple linear regression model, weight loss was directly associated with the follow up time and inversely associated with the initial waist circumference. Patients had a reduction of 0.05 z score points of BMI per month (95 percent confidence intervals –0.07 to –0.025; p < 0.001), while adhering to the program. The overall compliance with the three months treatment period was 59 percent. Conclusions: In children and teenagers, a multidisciplinary management of obesity achieves a sustained weight loss, that ifs proportional to the lapse of adherence to the program.

Hipertiroidismo y síndrome de Down: caso clínico / Hyperthyroidism and Down syndrome: a present diagnosis

A female patient with Down Syndrome and without cardiac defects. During infancy, she had low weight increment secondary to repeated hospital admissions due to obstructive respiratory tract episodes. In addition, she attends regularly to the gastroenterology clinic due to intermittent diarrhea. At the age of 9.4 years-old, she presented liquid stools 5-6 times/day, associated to a decrease of 7 kg in 5 months and marked hyperactivity. She is admitted with tachycardia, arterial hypertension and high liver enzymes (SGOT = 63 U/1 and SGPT = 97U/1). The ECG showed sinus tachycardia. She is discharged without etiological diagnosis. In the mean time, annual thyroid function requested for endocrinology control showed TSH < 0,1 uUI/ml, T3 = 482 ng/dl and total T4 = 15,4 ug/dl, evidencing clear hyperthyroidism and beginning therapy with propylthiouracil 10 mg/kg/day and propanolol 1,3 mg/kg/day. After 3 weeks, the patient showed less hyperactivity, normal stools, normal sleep-awake cycle and recovered weight. By 6 weeks, thyroid hormones and transaminases were within normal ranges.

Objetivo: Describir una asociación poco frecuente de Síndrome de Down con Hipertiroidismo. Caso Clínico: Paciente de sexo femenino, portadora de síndrome de Down, sin antecedentes de cardiopatía congénita. Evolucionó con mal incremento ponderal en el período de lactante, hospitalizaciones repetidas por cuadros respiratorios obstructivos. En control en gastroenterología por episodios de diarrea intermitente, y en genética en forma regular. Cuadro actual se inicia a los 9,4 años, caracterizado por deposiciones líquidas 5-6 veces al día, asociado a baja de peso aproximada de 7 kg en 5 meses e hiperactividad. Se hospitalizó para estudio y se pesquisaron cifras tensionales elevadas y taquicardia. En perfil bioquímico aparece SGOT 63 U/1 y SGTP 97 U/1. Electrocardiograma informa taquicardia sinusal. Alta sin etiología clara, se solicita función tiroidea: TSH < 0,1 uUI/ml, T3 482 ng/dl, T4 total 15,4 ug/dl realizándose diagnóstico de hipertiroidismo. Inició terapia con propiltiouracilo 10 mg/kg/día y propanolol 1,3 mg/kg/día. A las 3 semanas de iniciado el tratamiento, la paciente presenta menor hiperactividad, deposiciones normales, regulación de la hiperactividad y ciclo sueño-vigilia, recuperando peso. A las 6 semanas, los niveles de T3, T4 y transaminasas eran normales. El hipertiroidismo se observa con mucha menor frecuencia que el hipotiroidismo en niños y adultos con síndrome de Down. En series numerosas de pacientes con trisomía 21, se describen en general un bajo porcentaje de casos de hipertiroidismo, dentro de los cuales se incluyen la enfermedad de Graves y la Hashitoxicosis.

Panhipopituitarismo y diabetes insípida secundarios a hipofisitis linfocitaria en una paciente con trisomia 12p / Panhypopituitarism and diabetes insipidus secondary to a lymphocytic hypophysitis in one patient with trisomy 12p

Lymphocytic hypophysitis (LH) is an uncommon inflammatory disease of the hypophysis. It's female to male ratio of appearance is 9:1. Pregnant women are more affected during the third trimester of pregnancy or postpartum. Clinical and radiological presentation can simulate a hypophyseal adenoma. We report a nonpregnant 13 years old adolescent, with a trisomy 12p, with panhypopituitarism, diabetes insipidus and a selar tumor. It was necessary to differentiate between a germinoma and a LH. The latter was confirmed with the hypophyseal biopsy.

Diabetes Mellitus tipo 1 (DM1) en niños menores de 5 años: Características al debut vs otros grupos etarios en Chile / Type I diabetes mellitus in Chilean children under 5 years-old: Onset characteristics in contrast with other age groups

Introducción: En los últimos años, se ha visto un aumento en la incidencia de DM1 en niños. Objetivo: Determinar frecuencia y características clínicas y de laboratorio al debut de DM1 en niños chilenos menores de 5 años, comparado con los de mayor edad. Pacientes y Métodos: Se estudiaron los datos clínicos y de laboratorio de pacientes que debutaron entre 1998-2003 en cuatro centros de Santiago. Se clasificaron en 3 grupos etarios (G): 0-4 (GI), 5-9 (GII) y 10-14 años (GIII) y se compararon según los parámetros descritos. Resultados: Un 19,7 por ciento de los pacientes eran menores de 5 años; GI (n = 27), seguido de aquéllos pertenecientes a GII (43,8 por ciento; n = 60) y GIII (36,5 por ciento; n = 50). El periodo de síntomas previo al diagnóstico fue más corto en GI; 18,4 ± 23,7 vs 26,4 ± 27,4 y 40,1 ± 60 días (p < 0,0001) y su nivel de HbA1c fue más baja; 10,1 ± 1,7 vs 11,8 ± 3,4 por ciento en GII (p < 0,0001) y 12,4 ± 2,6 por ciento en GIII (p = 0,028), respectivamente. No hubo diferencias en la glicemia inicial entre los grupos. La acidosis metabólica fue mayor en GI; pH 7,14 ± 0,1 vs 7,19 ± 0,2 (GII) y 7,26 ± 0,1 (GIII) (p < 0,0001) y presentaron más infecciones concomitantes (33 por ciento, 20 y 28 por ciento respectivamente; p > 0,05). Conclusiones: Un porcentaje importante de las DM1 se inicia en niños < 5 años. Este grupo presenta un cuadro más grave, con mayor acidosis, menores niveles de HbA1c y periodo previo de síntomas, por lo que debe existir alerta para el diagnóstico en este grupo etario.

Background: During the last years, an increase in the incidence of DM1 in infants has been observed. Objective: to study the number of children younger than 5 years-old diagnosed with DM1 and compare clinical and laboratory features with older children at DM1 onset. Method: Study of the clinical and laboratory characteristics in subjects diagnosed with DM1 from 1998 to 2003 in Santiago. Patients were classified according to age in 3 groups: 0-4 (GI), 5-9 (GII) and 10-14 years-old (GIII). Results: 19,7 percent cases were younger than 5 years-old (GI n = 27), GII (43,8 percent n = 60) and GIII (36,5 percent n = 50). A shorter duration of symptoms was observed in GI (18,4 ± 23,7 vs 26,4 ± 27,4) (p < 0,0001) and HbA1c levels were lower in GII (10,1 ± 1,7 vs 11,8 ± 3,4 percent) (p < 0,0001) and in GIII (12,4 ± 2,6 percent) (p = 0,028). Glucose levels were similar among groups (p>0,05) and metabolic acidosis was more severe in GI (pH 7,14 ± 0,1 vs 7,19 ± 0,2 in GII and 7,26 ± 0,1 in GIII) (p < 0,0001). A concomitant infectious disease was observed in GI (33 percent), GII (20 percent) and GIII (28 percent) (p > 0,05). Conclusions: An important percentage of DM1 in children presents in subjects younger than 5 years-old. This group showed acute and severe clinical presentation with longer duration of symptoms, severe acidosis and lower HbA1c levels. It is necessary to evaluate carefully in order to suspect the diagnosis in this group.

Análogos de insulina: en búsqueda del reemplazo fisiológico / Insulin analogues: searching for a physiological replacement

Insulin analogues, developed by molecular engineering, have structural changes in the A and B insulin chains. These modifications change their action profile, rendering insulin replacement closer to physiology. Rapid acting analogues like lispro, aspart and glulisine, are absorbed rapidly from the subcutaneous tissue to the circulation. In addition, two long acting insulin analogues have been developed: glargine and detemir. The combination of a long acting insulin, to maintain baseline levels, and multiple daily doses of a rapid acting analogue are the mainstay of basal-bolus therapy. Multiples studies have compared human insulin (NPH and regular) with insulin analogues in patients with type 1 or 2 diabetes mellitus, showing an improvement in the metabolic control, fewer hypoglycemic events and better quality of life. In summary, insulin analogues offer new therapeutic options and allow an individualized intensive treatment.

Prevalencia de sobrepeso y obesidad en niños que se controlan en pediatría ambulatoria en Clínica Las Condes / Prevalence of overweight (OW) and obesity (O) in children attending the paediatric unit of the Clínica Las Condes

La obesidad infantil ha aumentado en Chile y con ella sus riesgos a largo plazo. Objetivo: Determinar la prevalencia de sobrepeso (SP) y obesidad (O) en niños controlados en un centro privado en Chile (Clínica Las Condes = CLC). Pacientes y Métodos: Estudio prospectivo en un año de 1.310 niños entre 2 y 18 años (51,6 por ciento hombres) de 7,19 ± 4,02 años de edad promedio. Se consignó edad, sexo, antropometría, y se calculó Índice de Masa Corporal (IMC, kg/m2) absoluto y percentil (p) y el porcentaje peso/talla ( por ciento P/T). Resultados: Los pacientes se distribuyeron en 3 grupos etarios: 45,7 por ciento entre 2-5, 29,5 por ciento entre 6-10 y 24,8 por ciento >10 años. Un 66,8 por ciento estaba eutrófico (IMC p10-85), SP 13,9 por ciento (IMC p85-95), O 12 por ciento (IMC > p95) y bajo peso (BP) 7,3 por ciento (IMC < p10), sin diferencias según sexo ni grupo etario. Conclusiones: La prevalencia de BP, SP y O en CLC es similar a la observada en niveles socioeconómicos medio-bajos chilenos. La mayor proporción entre 6-10 años hace indispensable su prevención desde la etapa de lactante.