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

; Pizarro, Carolina

; Camacho-Guillén, Patricia

; Codner, Ethel

; Soto, Néstor

; Pérez-Bravo, Francisco

Archives of Endocrinology and Metabolism

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Fev 2018, Volume 62 Nº 1 Páginas 34 - 40

Resumo: En | Texto: En | PDF: En

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.

https://doi.org/10.20945/2359-3997000000006 2768 downloads

De la bomba de insulina y el monitoreo continuo de glucosa al páncreas artificial
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Apablaza, Pamela

; Soto, Néstor

; Codner, Ethel

Revista médica de Chile

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Mai 2017, Volume 145 Nº 5 Páginas 630 - 640

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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.

12430 downloads

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

; Araya, Verónica

; Lanas, Alejandra

; Sapunar, Jorge

; Arrese, Marco

; Aylwin, Carmen Gloria

; Bezanilla, Carmen Gloria

; Carrasco, Elena

; Carrasco, Fernando

; Codner, Ethel

; Díaz, Erik

; Durruty, Pilar

; Galgani, José

; García, Hernán

; Lahsen, Rodolfo

; Liberman, Claudio

; López, Gloria

; Maíz, Alberto

; Mujica, Verónica

; Poniachik, Jaime

; Sir, Teresa

; Soto, Néstor

; Valderas, Juan

; Villaseca, Paulina

; Zavala, Carlos

Revista médica de Chile

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Mai 2015, Volume 143 Nº 5 Páginas 627 - 636

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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.

40781 downloads

La pubertad en niños chilenos muestra un adelantamiento en el inicio del crecimiento testicular
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Gaete, Ximena

; García, Roberto

; Riquelme, Joel

; Codner, Ethel

Revista médica de Chile

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Mar 2015, Volume 143 Nº 3 Páginas 297 - 303

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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.

3914 downloads

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
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Angel B, Bárbara

; Codner, Ethel

; Arredondo O, Miguel

; Salas P, Francisca

; Pizarro A, Carolina

; Pérez B, Francisco

Revista médica de Chile

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Set 2012, Volume 140 Nº 9 Páginas 1109 - 1115

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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.

4392 downloads

A rational approach to the diagnosis of polycystic ovarian syndrome during adolescence
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Merino, Paulina M.

; Codner, Ethel

; Cassorla, Fernando

Arquivos Brasileiros de Endocrinologia & Metabologia

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Nov 2011, Volume 55 Nº 8 Páginas 590 - 598

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

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.

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.

11416 downloads

Polimorfismo -174 G/C del gen promotor de interleuquina 6 en mujeres con diabetes mellitus tipo 1
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PÉREZ-BRAVO, FRANCISCO

; SOTO M, FRANCISCA

; LÓPEZ A, PATRICIA

; EYZAGUIRRE C, FRANCISCA

; CODNER, ETHEL

Revista médica de Chile

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Fev 2011, Volume 139 Nº 2 Páginas 158 - 164

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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% versus 14.1%, 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.

4033 downloads

Diagnóstico del Síndrome de Ovario Poliquístico: nuevos fenotipos, nuevas incógnitas
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Merino, Paulina

; Schulin-Zeuthen, Carolina

; Codner, Ethel

Revista médica de Chile

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Ago 2009, Volume 137 Nº 8 Páginas 1071 - 1080

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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.

103729 downloads Citado 4 vezes em SciELO

Hipopituitarismo congénito: Experiencia en 23 casos
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Lammoglia, Juan Javier

; Eyzaguirre, Francisca

; Unanue, Nancy

; Román, Rossana

; Codner, Ethel

; Cassorla, Fernando

; Mericq, Verónica

Revista médica de Chile

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Ago 2008, Volume 136 Nº 8 Páginas 996 - 1006

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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.

29949 downloads Citado 1 vez em SciELO

10.

Utilidad del estudio molecular de CYP21A2 en el manejo prenatal de hiperplasia suprarrenal congénita: detección de dos nuevas mutaciones en Chile
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Merino, Paulina

; Bachega, Tania

; Céspedes, Pablo

; Trejo, León

; Billerbeck, Ana Elisa

; Codner, Ethel

Revista médica de Chile

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Nov 2007, Volume 135 Nº 11 Páginas 1450 - 1455

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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

4835 downloads Citado 1 vez em SciELO

11.

Edad de la menarquia y su relación con el nivel socioeconómico e índice de masa corporal
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Hernández, M Isabel

; Unanue, Nancy

; Gaete, Ximena

; Cassorla, Fernando

; Codner, Ethel

Revista médica de Chile

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Nov 2007, Volume 135 Nº 11 Páginas 1429 - 1436

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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

28505 downloads

12.

Incidencia de diabetes mellitus tipo 1 en Santiago de Chile: análisis por comunas de la Región Metropolitana en el período 2000-2004
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Carrasco P, Elena

; Angel B, Bárbara

; Codner, Ethel

; García D, Diego

; Ugarte P, Francisca

; Bruzzone V, M Eugenia

; Pérez B, Francisco

Revista médica de Chile

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Out 2006, Volume 134 Nº 10 Páginas 1258 - 1264

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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

13300 downloads

13.

Glicemia de ayuno versus prueba de tolerancia oral a la glucosa en la detección de intolerancia a la glucosa en niños y adolescentes obesos
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Gallardo T, Vivian

; Avila A, Alejandra

; Unuane M, Nancy

; Codner, Ethel

Revista médica de Chile

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Set 2006, Volume 134 Nº 9 Páginas 1146 - 1152

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

Background: Recently, the cut-off point for normal fasting glucose (FG) level, was decreased to 100 mg/dl. Aim: To determine the frequency of abnormal carbohydrate abnormalities in children with obesity and evaluate if the fasting glucose level is a useful tool for the screening of glucose intolerance (GI). Patients and methods: Children and adolescents, referred for evaluation of obesity were evaluated with an oral glucose tolerance test (OGTT) and FG. The sensitivity of FG for detection of GI, using the 100 and 110 mg/dl cut-off point, was evaluated. Results: We studied 186 patients (125 females) aged 12.1 (range: 5.4-19.3) years with a body mass index (BMI) of 29.9 (18.3-44.6) kg/mt² and a BMI Z score of 2.1 (1.7-3.2). Seven patients (3.8%) had abnormalities in the carbohydrate metabolism. The sensitivity of FG for the detection of GI using the 100 and 110 mg/dl cut-off values was 42.9 and 14.3%, respectively. Receiver operating characteristic (ROC) curves showed that the optimal diagnostic level for FG corresponds to 80 mg/dl (sensitivity: 85.7% and specificity of 74.9%). Conclusions: An abnormal carbohydrate metabolism was detected in 3.8% of the obese children and adolescents in this sample. FG of 100 mg/dl does not detect 57.1% of the patients with glucose intolerance. These data suggest that FG is not a useful screening tool for glucose intolerance in young patients

36096 downloads

14.

Análogos de insulina: en búsqueda del reemplazo fisiológico
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Eyzaguirre C, Francisca

; Codner, Ethel

Revista médica de Chile

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Fev 2006, Volume 134 Nº 2 Páginas 239 - 250

Resumo: En Es | Texto: En Es | PDF: En | PDF: Es

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

15856 downloads

15.

Response to the gonadotropin releasing hormone agonist leuprolide in immature female sheep androgenized in utero
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RECABARREN, SERGIO E

; SIR-PETERMANN, TERESA

; LOBOS, ALEJANDRO

; CODNER, ETHEL

; ROJAS-GARCÍA, PEDRO P

; REYES, VÍCTOR

Biological Research

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2005, Volume 38 Nº 2-3 Páginas 235 - 244

Resumo: En | Texto: En | PDF: En

Similar to women with Polycystic Ovary Syndrome (PCOS), female sheep treated prenatally with testosterone (T-females) are hypergonadotropic, exhibit neuroendocrine defects, multifollicular ovarian morphology, hyperinsulinemia and cycle defects. Hypergonadotropism and multifollicular morphology may in part be due to developmentally regulated increase in pituitary responsiveness to GnRH and may culminate in increased ovarian estradiol production. In this study, we utilized a GnRH agonist, leuprolide, to determine the developmental impact of prenatal testosterone exposure on pituitary-gonadal function and to establish if prenatal exposure produces changes in the reproductive axis similar to those described for women with PCOS. Eight control and eight T-females were injected intravenously with 0.1 mg of leuprolide acetate per kilogram of body weight at 5, 10 and 20 weeks of age. Blood samples were collected by means of an indwelling jugular vein catheter at 0, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 hours after leuprolide. Area under the curve (AUC) of LH response to leuprolide increased progressively between the three ages studied (P<0.05). AUC of LH in T-females was higher than in control females of the same age at 5 and 10 weeks of age (P<0.05), but similar at 20 weeks of age. AUC of estradiol response was lower at 10 but higher at 20 weeks of age in T-females compared to controls of the same age (P<0.05). Our findings suggest that prenatal T treatment alters the pituitary and ovarian responsiveness in a manner comparable to that observed in women with PCOS.

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