Differential Effect of 2 Hormonal Contraceptives on the Relative Telomere Length of Youth With Type 1 Diabetes.

Context: Adolescents and young women (AYA) with type 1 diabetes (T1D) may require hormonal contraception for an extended period. However, it is unclear what effect hormonal contraception has on telomere length, a marker of the risk for complications. Objective: To investigate the relative telomere length (RTL) in AYA with T1D (AYA-T1D) and healthy young women (AYA-C) after 18 months of combined oral contraception use (COC) with ethinyl estradiol/desogestrel, or a subdermal etonogestrel implant (IM). Methods: A nonrandomized prospective study was performed in which 39 AYA-T1D and 40 AYA-C chose the COC or the IM. RTL was measured by monochrome multiplex-quantitative PCR in DNA from peripheral blood mononuclear cells (PBMC). The impact of contraceptives and clinical variables on RTL was assessed using lineal regression analysis. Results: Longer RTL compared to baseline was observed in AYA-T1D (P < .05) and AYA-C (P  < .01) after using the IM. However, the total of AYA and the AYA-C group treated with COC decreased RTL after 18 months of treatment compared to baseline (P < .05). The type of contraceptive used was determinant for the changes in RTL compared to baseline in all subjects and controls (P ≤ .006). For AYA-T1D, HbA1c levels were not associated with RTL, but the high-sensitivity C-reactive protein was negatively related with the changes in RTL at 18 months compared to baseline (standardized R2 : 0.230, P  = .003). Conclusion: IM was associated with longer RTL in AYA-T1D and AYA-C. In contrast, a shortening of telomere length in PBMC was observed after using COC.

Expression of miR-155, miR-146a, and miR-326 in T1D patients from Chile: relationship with autoimmunity and inflammatory markers

ABSTRACT Objective The aim of this research was to analyze the expression profile of miR-155, miR-146a, and miR-326 in peripheral blood mononuclear cells (PBMC) of 47 patients with type 1 diabetes mellitus (T1D) and 39 control subjects, as well as the possible association with autoimmune or inflammatory markers. Subjects and methods Expression profile of miRs by means of qPCR using TaqMan probes. Autoantibodies and inflammatory markers by ELISA. Statistical analysis using bivariate correlation. Results The analysis of the results shows an increase in the expression of miR-155 in T1D patients in basal conditions compared to the controls (p < 0.001) and a decreased expression level of miR-326 (p < 0.01) and miR-146a (p < 0.05) compared T1D patients to the controls. miR-155 was the only miRs associated with autoinmmunity (ZnT8) and inflammatory status (vCAM). Conclusion Our data show a possible role of miR-155 related to autoimmunity and inflammation in Chilean patients with T1D.

De la bomba de insulina y el monitoreo continuo de glucosa al páncreas artificial / From insulin pump and continuous glucose monitoring to the artificial pancreas

Technology for diabetes care has undergone major development during recent decades. These technological advances include continuous subcutaneous insulin infusion (CSII), also known as insulin pumps, and real-time continuous glucose monitoring system (RT-CGMS). The integration of CSII and RT-CGMS into a single device has led to sensor-augmented pump therapy and more recently, a technology that has automated delivery of basal insulin therapy, known as hybrid system. These new technologies have led to benefits in attaining better metabolic control and decreasing the incidence of severe hypoglycemia, especially in patients with type 1 diabetes. This review describes the types of technologies currently available or under investigation for these purposes, their benefits and disadvantages, recommendations and the appropriate patient selection for their use. The clinical use of the hybrid system and artificial pancreas seem to be possible in the near future.

Expresión de miR-22 y miR-150 en diabetes mellitus tipo 1: posible asociación con autoinmunidad y características clínicas de la enfermedad / Expression of miR-22 and miR-150 in type 1 diabetes mellitus: Possible relationship with autoimmunity and clinical characteristics

Introducción: La diabetes tipo 1 (DM1) es una enfermedad autoinmune de etiología compleja. Diversos microARN (miR) han sido relacionados con la patogénesis de enfermedades autoinmunes. Objetivo: Analizar la posible asociación de miR-22 y miR-150 con autoinmunidad y gravedad clínica en la DM1. Pacientes y método: El estudio se realizó en células mononucleares periféricas de 20 pacientes con DM1 y 20 sujetos controles. La expresión de miR-22 y miR-150 se realizó por sondas TaqMan en células mononucleares periféricas a diferentes concentraciones de glucosa (basal, 11mM, 25mM). Resultados: Nuestros resultados muestran que la expresión de miR-22 está aumentada en pacientes con DM1 respecto de controles. Este efecto se observó en la condición basal de glucosa y disminuyó en condiciones 11 y 25mM de glucosa. La expresión de miR-150 fue menor en pacientes con DM1 versus controles. No hubo asociación de los niveles de miR-22 (condición basal) y miR-150 (condición 11mM) con el perfil de autoinmunidad ni la presencia de cetoacidosis. Conclusión: miR-22 y miR-150 no se asocian a los niveles de autoanticuerpos, pero sí al componente de cetoacidosis en DM1 (AU)

Background and objective: Type 1 diabetes (T1D) is an autoimmune disease of complex aetiology. Several microRNAs (miR) have been linked to the pathogenesis of autoimmune diseases. To analyze the possible association of miR-22 and miR-150 with autoimmunity and clinical severity of T1D. Patients and methods: The study was performed in peripheral blood mononuclear cells of 20 patients with T1D and 20 control subjects. The expression of miR-22 and miR-150 was performed in peripheral blood mononuclear cells using TaqMan probes to different glucose concentrations (baseline, 11mm, 25mm). Results: Our results suggest that the expression of miR-22 is increased in T1D patients compared to the controls. This effect was observed in baseline glucose conditions and decreased in 11 and 25mM of glucose. The expression of miR-150 was lower in T1D patients versus the controls. There was no correlation between the autoimmune profile and the two studied miRNAs. miR-22 (baseline condition) and miR-150 (11mM condition) or the ketoacidosis component. Conclusion: miR-22 and 150 were not associated with the autoimmune component present in T1D patients (AU)

II Consenso de la Sociedad Chilena de Endocrinología y Diabetes sobre resistencia a la insulina

Insulin resistance is a prevalent condition commonly associated with unhealthy lifestyles. It affects several metabolic pathways, increasing risk of abnormalities at different organ levels. Thus, diverse medical specialties should be involved in its diagnosis and treatment. With the purpose of unifying criteria about this condition, a scientific-based consensus was elaborated. A questionnaire including the most important topics such as cardio-metabolic risk, non-alcoholic fatty liver disease and polycystic ovary syndrome, was designed and sent to national experts. When no agreement among them was achieved, the Delphi methodology was applied. The main conclusions reached are that clinical findings are critical for the diagnosis of insulin resistance, not being necessary blood testing. Acquisition of a healthy lifestyle is the most important therapeutic tool. Insulin-sensitizing drugs should be prescribed to individuals at high risk of disease according to clinically validated outcomes. There are specific recommendations for pregnant women, children, adolescents and older people.

La pubertad en niños chilenos muestra un adelantamiento en el inicio del crecimiento testicular / Age of onset of puberty in Chilean boys according to testicular volume and Tanner stage

Background: A secular trend towards a younger age of puberty onset has been reported in Chilean girls. Aim: To evaluate the age of onset of puberty and prevalence of early puberty in Chilean boys. Material and Methods: A pediatric endocrinologist examined 319 children attending schools in central Santiago. Pubertal development was assessed by testicular volume (TV) and genital inspection (GI) using Tanner graduation. Precocious and early puberty development was diagnosed if TV ≥ 4 ml or GI > stage 2 occurred in boys younger than 9 years and at 9-10 years of age, respectively. Results: Pubertal onset occurred at 10.2 ± 1.5 years according to TV and at 11.1 ± 1.6 years according to GI (p < 0.01). Before the age of nine, 15.2% of children had a VT ≥ 4 ml, 3% had genital changes in GI and only 3% had both changes simultaneously. Early puberty was observed in 23.8% of children according to TV and 9.5% according to GI. However, no child of less than 11 years old had a TV ≥ 4 ml, genital changes and pubic hair simultaneously. Late pubertal stages occurred at the same age according to both criteria used. Body mass index z score was not associated with the age of pubertal onset. Conclusions: Testicular enlargement occurs one year earlier than changes in genitalia according to inspection. Testicular growth, but not late stages of puberty, are occurring one year earlier than previously reported in Chile 10 years ago.

Expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito T-citotóxico (CTLA4) en pacientes chilenos con diabetes tipo 1 / Decreased caspase 3 expression and cytotoxic T lymphocyte antigen-4 polymorphism in Chilean patients with type 1 diabetes

Background: Several polymorphisms of the CTLA4 gene have been associated with autoimmune diseases. The activation of induced cell death is the major event and caspase 3 represents the main protein for the apoptotic machinery, especially in lymphocytes. Aim: To correlate CTLA4 polymorphisms with caspase 3 expression in peripheral blood mononuclear cells (PBMC) simulating in vitro the glucose effect. Material and Methods: CTLA4 polymorphisms were determined by restriction fragment length polymorphisms (RFLPs). PBMC from 21 patients with type 1 diabetes aged 8.5 ± 4.3 years and 21 healthy subjects aged 18.3 ± 1.8 years, were stimulated under normal (5 mM) and toxic (14 mM) glucose conditions to assess its effect on the expression and activity of caspase 3. Relative abundance of caspase 3 mRNA was measured by semi quantitative RT-PCR and its activity, by a colorimetric assay. Results: When stimulated with 14mM glucose, PBMC of G allele carriers with type 1 diabetes had significantly lower relative mRNA abundance of caspase 3 (median value = 0.12, range 0.01-0.70 AU) compared with non-carriers (median value = 0.81, range 0.06-1.09 AU). When the incubation was carried out with the lower glucose concentration, a similar profile of caspase 3 activity was observed in diabetic patients carrying G allele (median value = 0.57, range 0.13-1.20 AU) as compared with non-carriers (median value = 0.89, range 0.14-5.50 AU). No significant changes after stimulating with glucose, were observed in PBMCs of the control group. Conclusions: PBMC of recently diagnosed patients with T1D, carrying the G allele in + 49A/G polymorphisms of CTLA4, have a decreased expression and activity of caspase 3.

A rational approach to the diagnosis of polycystic ovarian syndrome during adolescence / Uma abordagem racional do diagnóstico da síndrome dos ovários policísticos na adolescência

Polycystic ovarian syndrome (PCOS) is a lifelong disorder characterized by hyperandrogenism and ovulatory dysfunction, with a wide spectrum of clinical symptoms and signs. Three different sets of diagnostic criteria have been established in order to define this disease in adult women, but there is controversy regarding the use of these criteria in adolescence. During puberty, the adult criteria for ovulatory dysfunction does not seem applicable, because an irregular menstrual pattern and a decreased ovulatory rate is a physiologic event during this period of life. Also, a higher prevalence of polycystic ovarian morphology (PCOM) may be observed during this period, so PCOM is not a useful criterion to define PCOS in young women. These findings suggest that a key factor to diagnose to PCOS during adolescence is hyperandrogenism. In addition, since PCOM is not clearly associated with hyperandrogenism during this period of life, the term "polycystic ovarian syndrome" during adolescence creates confusion and may be misleading.

A síndrome dos ovários policísticos (SOP) é uma desordem que afeta pacientes por toda a vida e é caracterizada por hiperandrogenismo e disfunção ovariana, com um amplo leque de sintomas e sinais clínicos. Três diferentes conjuntos de critérios diagnósticos foram estabelecidos para definir essa doença em mulheres adultas, mas existem controvérsias relacionadas ao uso desses critérios na adolescência. Durante a puberdade, o critério de disfunção ovariana usado em adultos não parece aplicável, porque um padrão menstrual irregular e uma menor taxa de ovulação são eventos fisiológicos nesse período da vida. Além disso, uma maior prevalência de morfologia ovariana policística (MOP) pode ser observada nesse período, de forma que a MOP não é um critério útil para se definir a SOP em mulheres jovens. Esses achados sugerem que o hiperandrogenismo é um fator-chave para o diagnóstico da SOP na adolescência. Além disso, como a MOP não está claramente associada com o hiperandrogenismo durante esse período da vida, o termo "síndrome dos ovários policísticos" durante a adolescência cria confusão e pode ser errôneo.

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.

Diagnóstico del Síndrome de Ovario Poliquístico: nuevos fenotipos, nuevas incógnitas / Current Diagnosis of Polycystic Ovary Syndrome: Expanding the phenotype but generating new questions

Polycystic ovarian syndrome (PCOS), includes a wide spectrum of clinical symptoms and signs. Three different diagnostic classifications have been proposed to define this disease. The first one, published in 1990, known as the "NIH criteria" requires the simultaneous presence of hyperandrogenism and menstrual dysfunction in order to diagnose PCOS. Later on, in 2004, an expert panel met in Rotterdam and added to the previous criteria the presence ofpolycystic ovarian morphology (PCOM) detected by transvaginal ultrasonography The later classification broadened the spectrum of PCOS and also included women with oligomenorrhea and PCOM without hyperandrogenism or hyperandrogenism and PCOM without menstrual dysfunction. Finally, the Androgen Excess Society, published in 2006 new diagnostic criteria which required the presence of clinical or biochemical hyperandrogenism, with either PCOM or menstrual dysfunction to diagnose PCOS. We review the different classifications employed in the diagnosis of PCOS, the diverse phenotypes that may lead to the diagnosis of PCOS and their association with cardiovascular and metabolic complications.

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.

Hipopituitarismo congénito: experiencia en 23 casos / Congenital hypopituitarism: report of 23 cases

Background: Congenital hypopituitarism is an uncommon cause of hypophyseal insufficiency It is less common than growth hormone deficiency which has an incidence of 1:4.000 to 1:8.000 Uve newborns. Early diagnosis ofthis condition is important to prevent impairment of cognitive function, poor growth and alterations in metabolic profile in these patients. Aim: To report 23 patients diagnosed with congenital hypopituitarism. Material and methods: Retrospective review of clinical records of 23 patients (12 males) with congenital hypopituitarism, diagnosed during a 21 years period. In a group of 16 patients a molecular study was performed searching for mutations in HESX1, PROP-1 or POUF-1. Results: Short stature was the most frequent sign at the first evaluation, followed by neonatal hypoglycemia and presence of nistagmus, strabismus, atrophic optic nerve or malformations in the middle Une showed in CNS imaging, suggesting septo-optic-dysplasia. All male patients diagnosed during neonatal period, exhibited micropenis. CNS images showed isolated hypophyseal hypoplasia or associated to an ectopic neurohypophysis in most patients. No patient in the subgroup subjected to molecular analysis had any of the mutations in the searched genes. Conclusions: The diagnosis of hypopituitarism must be based on clinical grounds, speciaUy when hypoglycemia, prolonged jaundice, micropenis or midline alterations are found in the neonatal period.

Asociación del polimorfismo Fok I del gen del receptor de vitamina D (VDR) con concentraciones plasmáticas del factor transformador de crecimiento Beta1 e interferón gamma en la diabetes mellitus tipo 1 / Association between Fok I vitamin D receptor (VDR) gene polymorphism and plasmatic concentrations of transforming growth factor-Beta1 and interferon gamma in type 1 diabetes mellitus

Fundamento y objetivo: Analizar el polimorfismo Fok I del gen del receptor de vitamina D (VDR) y su relación con la susceptibilidad a desarrollar diabetes tipo 1. Se realizó un estudio de casos y controles y se relacionaron los genotipos del VDR con las concentraciones circulantes de 25(OH)-vitamina D y las concentraciones séricas de factor transformador de crecimiento ß1 (TGF-ß1) e interferón gamma (INF-*). Pacientes y método: Se analizaron 151 casos de diabetes tipo 1 y 182 controles sanos no relacionados. Se amplificó el exón 2 del gen VDR mediante reacción en cadena de la polimerasa. Los genotipos se obtuvieron mediante análisis de fragmentos de restricción. La concentración de 25(OH) vitamina D se determinó por radioinmunoanálisis y las de las citocinas TGF-ß1 e INF-*, por enzimoinmunoanálisis. Resultados: La distribución del polimorfismo Fok I no mostró diferencias entre casos y controles. El grupo de niños diabéticos mostró valores más altos de TGF-ß1 (mediana, 282,6 pg/ml; intervalos, 131,8-3.031,4) que los niños controles (mediana, 232,2 pg/ml; intervalos, 135,7-506,5) (p < 0,0038). También se observaron valores aumentados de INF-* (mediana, 121,1 pg/ml; intervalos, 5,3-228,8) en los casos comparados con los controles (mediana, 89,6 pg/ ml; intervalos, 10,9-117,2) (p < 0,0004). Los pacientes diabéticos portadores del genotipo ff mostraron concentraciones de 25(OH) vitamina D menores que los portadores del alelo F: media (desviación estándar) de 23,1 (5,9) frente a 27,9 (10,3) ng/ml (p < 0,03). De forma similar, los diabéticos portadores del genotipo ff mostraron valores aumentados de TGF-ß1 al compararlos con los genotipos portadores del alelo F (298,5 frente a 276,6 pg/ml; p < 0,05). Conclusiones: El polimorfismo Fok I del VDR podría tener un papel marginal en la alteración inmunológica que se desarrolla en la diabetes tipo 1 a través de una posible modulación de la vitamina D

Background and objective: In order to assess whether Fok I vitamin D receptor gene (VDR) polymorphism is involved in the genetic susceptibility of type 1 diabetes, a case-control study was conducted and VDR genotypes were related to serum concentrations of 25(OH) vitamin D and cytokines transforming growth factor ß1 (TGF-ß1) and interferon gamma (INF-*). Patients and method: 151 incident cases of type 1 diabetes and 182 non related healthy controls from Santiago were studied for VDR polymorphisms in peripheral blood DNA. Exon 2 (Fok I) segments were amplified by polimerase chain reaction and analyzed by means of restriction fragment length polymorphism to determine each corresponding genotype. Differences for allele, genotype and serological markers as 25(OH) vitamin D, TGF-ß1 and INF-* levels distribution between patients and controls were analyzed. Results: Fok I polymorphism distribution analysis showed no differences between patients and controls. Among diabetics, higher levels of TGF-ß1 (median, 282.6 pg/ml; range, 131.8-3,031.4) were observed compared with healthy children (median, 232.2 pg/ml; range, 135.7-506.5) (p < 0.0038). Similar results were observed for INF-* concentrations (median, 121.1 pg/ml, and range, 5.3-228.8, in cases, and median, 89.6 pg/ml, and range, 10.9-117.2 in controls) (p < 0.0004). The diabetic carriers of the ff genotype showed low levels of 25(OH) vitamin D compared with the carriers of the F allele: mean (standard deviation), 23.1 (5.9) versus 27.9 (10.3) ng/ml (p < 0.03). A similar result was observed for TGF-ß1 concentrations in diabetic carriers of ff genotype and patients carriers of the F allele (298.5 versus 276.6; p < 0.05). Conclusions: Fok I polymorphism of VDR could have a marginal role in the immunologic disturbance in type 1 diabetes

Diabetes mellitus neonatal transitoria por duplicación paterna 6q24 / Transient neonatal mellitus diabetes due to paternal duplication 6q24

Neonatal diabetes mellitus is defined as severe hyperglycemia beginning during the first six months of life, lasting at least one month and needing insulin as a treatment. The incidence is about 1 in 200.000 born alive. We report a preterm female newborn, small for gestational age, whose actual age is 19 months. At the third day of life she became severely ill, with serious shock, losing 20 percent of her weight at birth. Laboratory work-up showed a blood glucose level of 633 mg/dl, hypernatremia, metabolic acidosis and renal failure. During the initial 4 months she was treated with insulin infusions that were tapered and finally discontinued at four months of age. The molecular study of this patient showed abnormal maternal methylation at chromosome 6 and the novo paternal duplication of 6q24.

Edad de la menarquia y su relación con el nivel socioeconómico e índice de masa corporal / Age of menarche and its relationship with body mass index and socioeconomic status

Background: A decline in the age of menarche was observed from early 1900s to the 1970s. However, it is not known if a further decline ocurred thereafter. Aim: To evaluate the age of menarche in girls from Santiago, Chile and its relationship with body mass index (BMI) and socioeconomic status. Material and Methods: We studied 1302 healthy girls aged 7 to 19 years. Age of menarche was evaluated through a questionnaire to the patient and her parents. Kaplan-Meier curves were used to determine age of menarche and Cox regression analysis was employed to evaluate the effect of the type of school and BMI on the age of menarche. Results: The mean age at menarche was 12.7±0.04 years. Girls from public and private schools had their period at 12.5±0.1 and 13.05±0.05 years respectively. A negative correlation between z scores for BMIand age of menarche was observed (r-0.3: p =0.001). Girls whose menarche occurred before 11.5 years had higher z scores for BMI and a larger proportion were overweight, compared to girls who had menarche later. Cox regression analysis showed that after adjusment for BMI, age of menarche was similar in both types of schools. Conclusions: Age of menarche is ocurring three months earlier in girls from public schools, which is associated with higher z scores for BMI. Type of school, a marker of socio-economic status in Chile, affects timing of menarche due to differences in body mass index.

Utilidad del estudio molecular de CYP21A2 en el manejo prenatal de hiperplasia suprarrenal congénita: detección de dos nuevas mutaciones en Chile / Molecular study of CYP21A2 gene for prenatal diagnosis of congenital adrenal hyperplasia: Report of a family

Prenatal treatment of pregnancies at risk of congenital adrenal hyperplasia (CAH) may prevent ambiguous genitalia in female fetuses. We present the prenatal treatment performed in an extended family with two mutations. The proband, a boy with CAH-salt losing form, and his relatives were studied. The proband's paternal uncles/aunts were married to the maternal aunts/uncles, respectively. The relatives had normal basal and stimulated 170HProgesterone levels, which did not clarify their carrier status. The CYP21A2 gene was sequenced. The proband and the paternal relatives harbored a Q318X, R483W mutation in one alíele. The maternal relatives and the proband exhibited an R483 frameshift mutation. Early dexametasone treatment was given during two pregnancies and stopped when male gender was confirmed by early ultrasonography Both newborns were healthy and had normal 170HProgesterone levels. This family had three mutations which abolish the 21-hydroxilase activity. Two mutations were detected in codon 483 of CYP21A2 gene, exon 10, which have not been reported previously in Latin-America. The molecular study performed in this family allowed us to give an appropriate genetic counseling and prenatal treatment.

Incidencia de diabetes mellitus tipo 1 en Santiago de Chile: análisis por comunas de la Región Metropolitana en el período 2000-2004 / Type 1 diabetes mellitus incidence in Santiago, Chile: Analysis by counties in the period 2000-2004

Background: There are great geographical differences in the incidence of type I diabetes mellitus. Aim: To determine the incidence rate of type 1 diabetes mellitus (DM1) in the Metropolitan Region of Santiago, Chile from January 1, 2000 to December 31, 2004 and to observe the distribution of cases in the different counties of Santiago. Material and methods: All the cases diagnosed with DM1 in the Metropolitan Region who fulfilled the following requirements were included in the study: age of onset <15 years, insulin treatment from onset, permanent residency in the area, and a diagnosis made between January, 2000 and December, 2004. Results: The incidence of DM1 was 6.58/100.000 inhabitants/year, and showed a significant increase from 2001 to 2004 (5.44 and 8.33 inhabitants/year, respectively, p <0.04). The incidence of DM1 also increased significantly in children younger than 4 years old. The incidence by counties exhibited large differences, ranging from 1,5 to 26,6/100.000 inhabitants. Counties with higher income, urbanization and low aborigine component showed a high incidence rate of type 1 diabetes. Conclusions: In the Metropolitan Region of Santiago, an increase of the incidence of DM1 has occurred in the period 2000-2004, especially in children younger than 4 years old. Large differences among counties were observed.