Altered cardiometabolic profile in girls with central precocious puberty and adipokines: A propensity score matching analysis.

OBJECTIVE: To compare cardiometabolic factors and adipokines between patients with recently diagnosed CPP and controls without CPP, paired by BMI Z scores (BMIz) and classified into girls with adequate nutritional status and girls who are overweight or obese. METHODS: This cross-sectional study was performed from January 2012 to May 2015 at two tertiary care pediatric centers in Mexico City. We included female patients with idiopathic CPP without other chronic pathology and healthy controls. Patients were divided into groups, BMI < 85th and BMI ≥ 85th percentile, according to 2000 CDC Growth Charts. Anthropometric data and fasting plasma concentrations of lipids, glucose, insulin, and leptin were assessed. RESULTS: There were 73 patients with CPP and 82 without CPP. Sixty-six patients were matched between the groups; no significant difference was noted between the groups according to zBMI. However, differences in the bone/chronological age relationship, birth weight and proportions in different Tanner stages were observed. Among girls with normal BMI, the percentage of body fat (24.6% vs 18.9%, p < 0.001), serum triglycerides (102.9 vs 54.3 mg/dl, p < 0.001), leptin (7.46 vs 5.4 ng/ml, p = 0.010) and free leptin (0.44 vs 0.29 ng/ml, p = 0.044) were higher in those with CPP; additionally, girls with CPP presented a higher proportion of hypertriglyceridemia. In the overweight/obese group, adiponectin levels were lower in girls with CPP (6.23 vs 7.28 pg/ml, p = 0.011). CONCLUSIONS: Girls with CPP and normal BMI at diagnosis had a worse cardiometabolic profile, as reflected by higher levels of free leptin, and higher proportion of hypertriglyceridemia than girls without CPP.

[Thyroid dysfunction due to 131I-metaiodobenzylguanidine in patients with neuroblastoma]. / Disfunción tiroidea por I131-Metayodo Benzilguanidina en pacientes con neuroblastoma.

INTRODUCTION: The treatment of advanced neuroblastoma includes chemotherapy, surgery, and radiotherapy with 131-I-Metaiodobenzylguanidine (131-I-MIBG). Despite strategies to protect thyroid function, its dysfunction is reported between 12 and 85%. OBJECTIVE: To identify the frequency of thyroid dys function in cases of neuroblastoma treated with 131-I-MIBG. PATIENTS AND METHOD: Cross-sectional study. We included all the cases with neuroblastoma treated with 131-I-MIBG between 2002 and 2015, with complete somatometry, and complete thyroid profile (TSH, free and total T3 and T4, and anti-thyroglobulin and antiperoxidase antibodies). RESULTS: 27 patients were identified out of which eleven died (40%). Out of the 16 surviving cases, 9 (56%) presented thyroid dysfunction: 2 (13%) cases with subclinical hypothyroidism and 7 (44%) cases with clinical hypothyroidism (3 cases due to psychomotor developmental delay and 4 due to growth deceleration). The patients presented cli nical manifestations at 16.1 months (1.2-66.3 months) after receiving the radiopharmaceutical at a cumulative dose of 142 mCi (96-391.5 mCi). No differences were found in the age at diagnosis, age at the start of treatment with 131-I-MIBG, the cumulative dose of 131-I-MIBG, and the time elapsed between the dose and the thyroid profile among the cases with or without thyroid dysfunction. Con clusions: 56% of patients with neuroblastoma had thyroid dysfunction. Most of the cases with hy pothyroidism were referred when thyroid dysfunction was clinically evident. A thyroid profile should be performed every 6 months, along with an annual endocrinological evaluation during the next 5 years in these patients.

Diabetes Drug Discovery: hIAPP1-37 Polymorphic Amyloid Structures as Novel Therapeutic Targets.

Human islet amyloid peptide (hIAPP1-37) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP1-37) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP1-37 aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs. The family of pharmaco-chaperones are modulators of the oligomerization and fibre formation of hIAPP1-37. When they interact with the amino acid in the amyloid-like steric zipper zone, they inhibit and/or delay the aggregation-oligomerization pathway by binding and stabilizing several amyloid structures of hIAPP1-37. Moreover, they can protect cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP1-37 oligomers. The modulation of proteostasis by the family of pharmaco-chaperones A-F is a promising potential approach to limit the onset and progression of diabetes and its comorbidities.

Association of leptin with cardiometabolic factors in schoolchildren and adolescents with congenital adrenal hyperplasia. / Asociación de leptina con factores cardiometabólicos en escolares y adolescentes con hiperplasia suprarrenal congénita.

Introduction: In congenital adrenal hyperplasia (CAH), obesity, hyperinsulinemia and leptin levels are increased. Objective: To identify the frequency of cardiometabolic risk factors (CRF) in children and adolescents with CAH and to explore the relationship with leptin levels. Method: Cross-sectional study of 40 patients who underwent anthropometric measurements and had fasting glucose, insulin, triglycerides, 17-hidroxyprogesterone, leptin, HDL and LDL-cholesterol assessed. The patients were classified according to the number of CRFs, and leptin levels were analyzed with the Kruskal-Wallis test. Pearson's correlation was applied between leptin, body mass index (BMI) z-score and body fat percentage. Results: Fifty percent of the patients had obesity and overweight, 59% had hypertriglyceridemia, 40%, hypoalphalipoproteinemia, 27.5%, high LDL-cholesterol and 22.5% insulin resistance. There was positive correlation between leptin and body fat percentage (r = 0.64), BMI z-score (r = 0.55) and the number of CRFs (r = 0.65). In the obesity-adjusted multivariate analysis, leptin levels were associated with the number of CRFs. Conclusion: CAH had a high frequency of CRFs and leptin appeared to be associated with a more adverse cardiometabolic profile in subjects with obesity and overweight.

Introducción: En la hiperplasia suprarrenal congénita (HSC), la obesidad, la hiperinsulinemia y los niveles de leptina se encuentran incrementados. Objetivo: Identificar la frecuencia de los factores de riesgo cardiometabólico (FRC) en niños y adolescentes con HSC y explorar la relación con los niveles de leptina. Método: Estudio transversal de 40 pacientes a quienes se realizó somatometría y evaluación de glucosa, insulina, triglicéridos, 17-hidroxiprogesterona, leptina, colesterol HDL y LDL en ayuno. Los pacientes fueron clasificados por el número de FRC y se analizaron los niveles de leptina con Kruskal-Wallis. Se aplicó correlación de Pearson entre la leptina, puntuación Z del índice de masa corporal (zIMC) y porcentaje de grasa corporal. Resultados: 50 % de los pacientes presentó obesidad y sobrepeso, 59 % hipertrigliceridemia, 40 % hipoalfalipoproteinemia, 27.5 % colesterol LDL alto y 22.5 % resistencia a la insulina. Hubo correlación positiva entre leptina y porcentaje de grasa corporal (r = 0.64), el zIMC (r = 0.55) y el número de FRC (r = 0.65). En el análisis multivariado ajustado por obesidad, los niveles de leptina se asociaron con el número de FRC. Conclusión: La HSC tuvo alta frecuencia de FRC y al parecer la leptina se asoció con perfil cardiometabólico más adverso en sujetos con obesidad y sobrepeso.

RELATIONSHIP BETWEEN SERUM LEPTIN LEVELS AND WEIGHT GAIN IN GIRLS WITH CENTRAL PRECOCIOUS PUBERTY AT 1-YEAR FOLLOW-UP.

OBJECTIVE: Patients with central precocious puberty (CPP) may have increased serum leptin levels; however, it is not well known whether this increase differs between patients with and without obesity. Our objectives were to describe the changes in serum leptin in girls with CPP in the first 12 months after diagnosis based on body mass index (BMI) and to explore whether serum leptin level at CPP diagnosis is related to BMI z-score (BMIz) after a 1-year follow-up. METHODS: A prospective cohort study was performed. We included 42 girls with idiopathic CPP in Tanner stages II and III. Anthropometric measurements were performed, and serum leptin was measured at study initiation and after 12 months. Patients were stratified according to BMI category (30 with a BMI in the <94th percentile and 12 with a BMI in the >95th percentile). Study variables were compared. Correlations among leptin, BMIz, and body fat were assessed. RESULTS: Leptin increased gradually during the first year of treatment. In girls with a BMI in the <94th percentile at diagnosis, body fat percentage increased gradually during the first year of follow-up. CONCLUSION: Girls with a BMI in the <94th percentile have a greater risk of weight increase. Leptin level >10.5 ng/dL at diagnosis is a risk factor for weight gain after 1 year. ABBREVIATIONS: BMI = body mass index BMIz = BMI z-score CPP = central precocious puberty GnRHa = gonadotropin-releasing hormone analogue.

HLA Risk Haplotype: Insulin Deficiency in Pediatric Type 1 Diabetes.

BACKGROUND: Certain HLA class II haplotypes have long been related with the risk of developing type 1 diabetes. The presence of the HLA haplotype DRB1*04/DQA1*03/DQB1*03:02, together with specific ß-cell autoantibodies, contributes to the development and/or severity of insulin deficiency in type 1 diabetes. OBJECTIVE: To evaluate the association of HLA risk haplotype HLA-DRB1/-DQA1/-DQB1 with ß-cell function and antibody markers in recent-onset type 1 diabetes patients, their siblings, and controls. METHODS: We studied recently diagnosed type 1 diabetes pediatric patients, their siblings, and healthy controls, analyzing autoantibodies (anti-glutamic acid decarboxylase, anti-IA-2, and anti-insulin), HLA risk and protector haplotypes, and ß-cell function (plasma proinsulin, insulin and C-peptide). X2, ANOVA or Kruskal-Wallis and multiple logistic regression were used to analyze data. RESULTS: We included 46 patients, 72 siblings, and 160 controls. Prevalence of anti-tyrosine phosphatase-related islet antigen 2 and anti-glutamic acid decarboxylase antibodies was higher in patients than siblings and controls. We found risk haplotype DRB1*04/DQA1*03/DQB1*03:02 in 95.7% of patients vs. 51.87% of controls; DRB1*03:01/DQA1*05/DQB1*02 in 47.8% of patients vs. 8.12% of controls; and DRB1*14/DQA1*05/DQB1*03:01 in 2.2% of patients vs. 20.0% of controls. With DRB1*04/DQA1*03/DQB1*03:02, the prevalence of antibodies was significantly higher in patients, although not within any single group. In regression model based on insulin secretion, only anti-tyrosine phosphatase-related islet antigen 2 antibodies and age were associated with the risk haplotype. CONCLUSIONS: The DRB1*04/DQA1*03/DQB1*03:02 haplotype increased the risk for lower insulin, proinsulin, and C-peptide concentrations, suggesting an association with the severity of insulin deficiency in type 1 diabetes patients. This haplotype, added to antibody positivity, is a predictor of deficient insulin secretion in a Mexican pediatric population.

[Level of expression of gene CTSL and its correlation with natural killer T-Cells in mexican pediatric patients with recent-onset type 1 diabetes]. / Asociación de células NKT con la expresión del gen CTSL en población pediátrica mexicana con diabetes tipo 1 de reciente diagnóstico.

OBJECTIVE: To compare the level of expression of the gene CTSL and its correlation with NKT cells in patients with recent-onset type 1 diabetes (T1D), their siblings, and healthy controls. METHODS: Analytical cross-sectional design. Patients with T1D < 3 months evolution, their siblings, and healthy controls were included. Percentages and absolute numbers of NKT cells were measured with expression of the CTSL gene. RESULTS: 124 subjects: with T1D (n = 48), siblings (n = 44) and controls (n = 32) were included. HbA1c was greater and C-peptide lower in T1D than the other groups and sibling age was higher (p < 0.001). There were no differences in NKT cells between T1D (0.176 ± 0.202) and controls (0.118 ± 0.133), but the percentage was higher in siblings (0.246 ± 0.188; p = 0.002). Lower level of expression of the CTSL gene associated with both absolute number (r: 0.4607; 95% CI: -0.08425 to -0.7935; p = 0.043) and percentage of NKT cells (r: 0.4540; 95% CI: -0.0927 to -0.7903; p = 0.045) in the T1D group. CONCLUSIONS: Patients with T1D have lower percentage and absolute number of NKT cells compared to their siblings. NKT cells absolute numbers are correlated with the expression of CTSL in T1D patients.

Leptin/adiponectin ratio as a prognostic factor for increased weight gain in girls with central precocious puberty.

Objective: To determine if the leptin, adiponectin, and leptin/adiponectin ratio (LAR) can predict weight gain at the end of GnRH analogs (GnRHa) treatment in girls with central precocious puberty (CPP). Material and methods: Study design: prospective cohort. Serum levels of leptin and adiponectin were determined at diagnosis of CPP. Anthropometry was performed at diagnosis of CPP and every six-months, until treatment with GnRHa was discontinued and they presented menarche. Patients were divided according to BMI<94 and BMI>95 percentile at diagnosis of CPP. The outcome was the increased in weight gain (e.g., from normal weight to overweight) at the end of follow-up. Statistical analysis: repeated measures ANOVA test and Student's t-test were used to compare groups. Logistic regression analysis was used to evaluate the association of leptin and adiponectin levels, as well as LAR values with increased weight gain. Results: Fifty-six CPP patients were studied, 18 had BMI >95 percentile and 38 BMI <94 percentile. Of the 18 patients who initially had BMI >95th, two patients went from obesity to overweight, while among the 38 patients who started with BMI <94th, 21 (55.2%) increased their weight gain at the end of follow-up. This last group had higher leptin levels (8.99 ± 0.6 vs 6.14 ± 0.8, p=0.005) and higher LAR values compared to those who remained in the same weight (1.3 ± 0.5 vs 0.96 ± 0.56, p=0.01). In the logistic regression analysis, it was found that higher leptin levels and higher LAR values were associated with increased weight gain (RR 1.31, 95%CI 1.03-1.66, RR 4.86, 95%CI 1.10-21.51, respectively), regardless of birth weight, pubertal stage, age, and bone/chronological age ratio. Conclusions: In patients with CPP, leptin levels and higher LAR values appear to be associated with significantly greater weight gain during GhRHa treatment, particularly in girls starting with BMI < 94 percentile.

Burden in primary informal caregivers of children and adolescents with type 1 diabetes: Is it associated with depression, family dysfunction, and glycemic control?

Objective: The requirement of a chronic treatment and the increase in life expectancy in children with type 1 diabetes (T1D) leads to the possibility of caregiver burden. The aim of our study was to evaluate the burden in primary informal caregivers (PIC) of children and adolescents with type 1 diabetes and its association with depression, family dysfunction, and glycemic control. Materials and methods: A retrospective study was performed in PIC of children and adolescents with T1D. Zarit Burden Interview Scale (ZBIS) was used to evaluate caregiver burden. Beck Depression Inventory (BDI-II) was used to evaluate depression in PIC, and the Family APGAR questionnaire was used to evaluate the family functionality. Results: A total of 100 PIC of children and adolescents with T1D were included. Caregiver burden was found in 33% of caregivers. The total score of the Zarit scale was 41 (34-49); 19% had mild caregiver burden, and 14% had severe caregiver burden. According to the BDI-II, 82% had minimal depression, 11% mild depression, 5% moderate depression, and 2% severe depression. Family function was good in 69%; 13% had moderate dysfunction, and 18% had severe dysfunction. A positive correlation between caregiver burden and BDI-II score (r = 0.84; p = 0.001) and the grade of depression (r = 0.87; p = 0.001) was found. A logistic regression model showed that BDI-II score was associated with caregiver burden (OR 1.14; 95% CI 1.061-1.23; p = 0.001). A BDI-II cut off of 9 or more had a sensibility and specificity of 58% and 28%, respectively, for caregiver burden [AUC 0.751 (0.64-0.85); p = 0.001]. A BDI-II score ≥9 was a predictor of caregiver burden (OR 3.4; 95% CI 1.4-8.1; p = 0.008). Conclusion: Caregiver burden is present in more than one third of the PIC of patients with T1D and is associated with depression. A BDI-II score ≥9 is a predictor of caregiver burden which may be a point to take into account in the integral approach to the patient with T1D and his or her family nucleus.

Downregulation of SLC16A11 is Present in Offspring of Mothers with Gestational Diabetes.

BACKGROUND: Studies have identified that diseases in pregnancy affect fetal growth and development of the newborn. In Mexican population, the gene SLC16A11 has been identified as a factor that increases the risk of developing type 2 diabetes mellitus. To date, information is scarce about its expression in gestational diabetes mellitus (GDM); epigenetic modifications due to maternal hyperglycemic state could be identified early in fetal development. PURPOSE: This study aimed to determine the SLC16A11 expression and methylation status in umbilical cord blood of newborns offspring of mothers with or without GDM. METHODS: Cross-sectional, analytic study. Pregnant patients undergoing caesarean delivery with and without GDM in the Unidad Medica de Alta Especialidad Hospital de Gineco-obstetricia #4 Luis Castelazo Ayala, Instituto Mexicano del Seguro Social, were invited to participate. DNA was extracted from the mothers' blood cells, or umbilical cord blood cells of their newborns, and subjected to methylation status. Total RNA was used to evaluate the SLC16A11 expression by endpoint RT-PCR. Variables were analyzed with Student t. Values of p <0.05 were considered statistically significant. RESULTS: A SLC16A11 downregulation was observed for newborns, while methylation status was found in only 1 of 68 mother-child pairs. Somatometry of newborns showed no differences between groups. Differences were found in total cholesterol, triglycerides, ALT, glucose, and HbA1c. CONCLUSIONS: For the first time, a differential expression for SLC16A11 was observed in offspring. Downregulation in this gene expression could characterize the offspring from GDM. No difference was found in somatometry of newborns of mothers with and without GDM.

Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early ß-cell damage in obesity and diabetes.

BACKGROUND AND AIMS: This is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when ß-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early ß-cell damage. MATERIALS AND METHODS: We performed a multicentric collaborative, cross-sectional, analytical, ambispective and blinded study; the RIAO from pretreated samples (PTS) of sera of 146 pediatric patients with obesity or DM and 16 healthy children, were isolated, measured by sound indirect ELISA with novel anti-hIAPP cytotoxic oligomers polyclonal antibody (MEX1). We carried out morphological and functional studied and cluster-clinical data driven analysis. RESULTS: We demonstrated by western blot, Transmission Electron Microscopy and cell viability experiments that RIAO circulate in the blood and can be measured by ELISA; are elevated in serum of childhood obesity and diabetes; are neurotoxics and works as biomarkers of early ß-cell failure. We explored the range of evidence-based medicine clusters that included the RIAO level, which allowed us to classify and stratify the obesity patients with high cardiometabolic risk. CONCLUSIONS: RIAO level increases as the number of complications rises; RIAOs > 3.35 µg/ml is a predictor of changes in the current indicators of ß-cell damage. We proposed a novel physio-pathological pathway and shows that PCD affect not only elderly patients but also children. Here we reduced the gap between basic biomedical research, clinical practice and health decision making.

Puberty blockade: Clinical guideline for the diagnosis and treatment of precocious puberty.

The Mexican Society of Pediatric Endocrinology developed a clinical practice guide for the diagnosis and treatment of precocious puberty. This document presents recommendations related to the interventions for the inhibition of central precocious puberty. The detailed description of the methodology for the development of this guide and the grading system, as well as the synthesis of the evidence on which it is based can be consulted in this same supplement.

La Sociedad Mexicana de Endocrinología Pediátrica elaboró una guía de práctica clínica para el diagnóstico y el tratamiento de la pubertad precoz. Este documento presenta recomendaciones relacionadas con las intervenciones para inhibir la pubertad precoz central. La descripción detallada de la metodología para el desarrollo de esta guía y del sistema de gradación, así como la síntesis de la evidencia en la que se basa, pueden consultarse en este mismo suplemento.

Diagnosis of precocious puberty: clinical guideline for the diagnosis and treatment of precocious puberty.

The Mexican Society of Pediatric Endocrinology developed a clinical practice guide for the diagnosis and treatment of precocious puberty. This document presents recommendations related to the diagnosis of precocious puberty. The detailed description of the methodology for the development of this guide and the grading system, as well as the synthesis of the evidence on which it is based can be accessed in this same supplement.

La Sociedad Mexicana de Endocrinología Pediátrica elaboró una guía de práctica clínica para el diagnóstico y el tratamiento de la pubertad precoz. Este documento presenta recomendaciones relacionadas con el diagnóstico de pubertad precoz. La descripción detallada de la metodología para el desarrollo de esta guía y del sistema de gradación, así como la síntesis de la evidencia en la que se basa, pueden consultarse en este suplemento.

Methodology for the development of the Clinical guideline for the diagnosis and treatment of precocious puberty.

Background: The Mexican Society of Pediatric Endocrinology presents recommendations for the diagnosis and treatment of precocious puberty (PP), a condition defined as the development of sexual characteristics due to an increase in pituitary gonadotropin secretion before 8 or 9 years of age in girls and boys, respectively. Methods: Three systematic reviews were conducted: controlled clinical trials on interventions for PP treatment, diagnostic tests, and observational studies on the long-term effects of PP. The quality evaluation and data extraction from the studies were conducted by two independent reviewers. The Scottish Intercollegiate Guidelines Network and the Oxford Center for Evidence-Based Medicine systems were used for grading the quality of evidence for recommendations on intervention and diagnosis, respectively. Recommendations were submitted to a consensus by a Delphi method and were validated by another 143 certified pediatric endocrinologists through an online questionnaire. Results: The group generated 12 recommendations on the diagnosis of PP, seven on the diagnosis of secondary causes of PP, eight on interventions for inhibition of puberty, five on other interventions for PP treatment, and 14 for the monitoring and follow-up of these patients. The online questionnaires submitted to certified pediatric endocrinologists showed more than 90% of approval for each one of the recommendations. Conclusions: Although a high degree of consensus for the recommendations for diagnosis, treatment, and monitoring of PP among pediatric endocrinologists was achieved, most of these recommendations showed a low level of evidence.

Introducción: La Sociedad Mexicana de Endocrinología Pediátrica presenta recomendaciones para el diagnóstico y el tratamiento de la pubertad precoz (PP), condición definida como el desarrollo de caracteres sexuales por incremento en la secreción hipofisiaria de gonadotropinas antes de los 8 años en las niñas y de los 9 años en los niños. Métodos: Se realizaron tres revisiones sistemáticas de ensayos clínicos controlados sobre intervenciones para el tratamiento de la PP, pruebas diagnósticas y estudios observacionales sobre efectos a largo plazo de la PP. La evaluación de la calidad de los estudios y la extracción de datos se realizó por pares. La evidencia se graduó con el sistema de la Scottish Intercollegiate Guidelines Network (SIGN) y del Oxford Centre for Evidence-Based Medicine (OCEBM) para las recomendaciones sobre la intervención y el diagnóstico, respectivamente. Las recomendaciones generadas se sometieron a un consenso por el método Delphi y fueron validadas por otros 143 endocrinólogos pediatras certificados mediante un cuestionario en línea. Resultados: Mediante consenso se generaron 12 recomendaciones para el diagnóstico de PP, siete sobre diagnóstico de causas secundarias de PP, ocho sobre intervenciones para inhibición de la pubertad, cinco sobre otras intervenciones en PP y 14 para la monitorización del tratamiento y el seguimiento de estos pacientes. Se obtuvo más del 90% de aprobación para cada una de las recomendaciones por el grupo de endocrinólogos certificados que respondieron el cuestionario en línea. Conclusiones: Si bien se logró un alto grado de consenso para las recomendaciones para el diagnóstico, el tratamiento y la monitorización de la PP entre los endocrinólogos pediatras, el nivel de evidencia para la mayoría de estas recomendaciones resultó bajo.

Diagnosis of secondary causes of precocious puberty: Clinical guideline for the diagnosis and treatment of precocious puberty.

The Mexican Society of Pediatric Endocrinology developed a clinical practice guide for the diagnosis and treatment of precocious puberty. This document presents recommendations related to the diagnosis of secondary causes of central PP. The detailed description of the methodology for the development of this guide and the grading system, as well as the synthesis of the evidence on which it is based can be consulted in this same supplement.

La Sociedad Mexicana de Endocrinología Pediátrica elaboró una guía de práctica clínica para el diagnóstico y el tratamiento de la pubertad precoz. Este documento presenta recomendaciones relacionadas con el diagnóstico de causas secundarias de pubertad precoz central. La descripción detallada de la metodología para el desarrollo de esta guía y del sistema de gradación, así como la síntesis de la evidencia en la que se basa, pueden consultarse en este mismo suplemento.

Adjuvant interventions in the treatment of precocious puberty: Clinical guideline for the diagnosis and treatment of precocious puberty.

The Mexican Society of Pediatric Endocrinology developed a clinical practice guide for the diagnosis and treatment of precocious puberty. This document presents recommendations related to the complementary interventions for the treatment of precocious puberty besides puberty blockade. The detailed description of the methodology for the development of this guide and the grading system, as well as the synthesis of the evidence on which it is based, can be consulted in this same supplement.

La Sociedad Mexicana de Endocrinología Pediátrica elaboró una guía de práctica clínica para el diagnóstico y el tratamiento de la pubertad precoz. Este documento presenta recomendaciones relacionadas con intervenciones adyuvantes en el tratamiento de la pubertad precoz distintas de la inhibición de la pubertad. La descripción detallada de la metodología para el desarrollo de esta guía y del sistema de gradación, así como la síntesis de la evidencia en la que se basa, pueden consultarse en este mismo suplemento.

Monitoring during the treatment of precocious puberty: Clinical guideline for the diagnosis and treatment of precocious puberty.

The Mexican Society of Pediatric Endocrinology developed a clinical practice guide for the diagnosis and treatment of precocious puberty. This document presents recommendations related to the monitorization of the treatment and follow-up of patients with central precocious puberty. The detailed description of the methodology for the development of this guide and the grading system, as well as the synthesis of the evidence on which it is based, can be consulted in this same supplement.

La Sociedad Mexicana de Endocrinología Pediátrica elaboró una guía de práctica clínica para el diagnóstico y el tratamiento de la pubertad precoz. Este documento presenta recomendaciones relacionadas con la monitorización del tratamiento y el seguimiento de pacientes con pubertad precoz central. La descripción detallada de la metodología para el desarrollo de esta guía y del sistema de gradación, así como la síntesis de la evidencia en la que se basa, pueden consultarse en este mismo suplemento.

Synthesis of the evidence: Clinical guideline for the diagnosis and treatment of precocious puberty.

Three systematic reviews were conducted to formulate the recommendations on diagnosis, treatment and follow-up of patients with precocious puberty: interventions for the treatment of precocious puberty that included the outcomes of final or near-final height, mental health, metabolic health, health bone, or blockade success; comparative observational studies evaluating long-term outcomes in subjects with a history of precocious puberty; and diagnostic test accuracy studies for puberty.

Se realizaron tres revisiones sistemáticas para la formulación de las recomendaciones sobre diagnóstico, tratamiento y seguimiento de pacientes con pubertad precoz: intervenciones para el tratamiento de la pubertad precoz que incluyeran los desenlaces de talla final o casi final, salud mental, salud metabólica, salud ósea o éxito en el bloqueo; estudios observacionales comparativos que evaluaran desenlaces a largo plazo en sujetos con antecedentes de pubertad precoz; y por último, estudios de exactitud de prueba diagnóstica para pubertad.

Unpacking the aggregation-oligomerization-fibrillization process of naturally-occurring hIAPP amyloid oligomers isolated directly from sera of children with obesity or diabetes mellitus.

The formation of amyloid oligomers and fibrils of the human islet amyloid polypeptide (hIAPP) has been linked with ß- cell failure and death which causes the onset, progression, and comorbidities of diabetes. We begin to unpack the aggregation-oligomerization-fibrillization process of these oligomers taken from sera of pediatric patients. The naturally occurring or real hIAPP (not synthetic) amyloid oligomers (RIAO) were successfully isolated, we demonstrated the presence of homo (dodecamers, hexamers, and trimers) and hetero-RIAO, as well as several biophysical characterizations which allow us to learn from the real phenomenon taking place. We found that the aggregation/oligomerization process is active in the sera and showed that it happens very fast. The RIAO can form fibers and react with anti-hIAPP and anti-amyloid oligomers antibodies. Our results opens the epistemic horizon and reveal real differences between the four groups (Controls vs obesity, T1DM or T2DM) accelerating the process of understanding and discovering novel and more efficient prevention, diagnostic, transmission and therapeutic pathways.

Resistin levels are not associated with obesity in central precocious puberty.

OBJECTIVE: To compare serum resistin concentrations between prepubertal girls with a BMI > 85th percentile and girls with precocious puberty (CPP) who have and have not undergone GnRH analog treatment. PATIENTS AND METHODS: This is a cross-sectional study in girls with a BMI > 85th percentile and a median age of 8 years. We included 31 girls with CPP who did not receive treatment (CPPoT), 23 girls with CPP who were treated with leuprolide (CPPT), 22 prepubertal girls and 24 pubertal girls. Anthropometric data and the fasting plasma concentrations of lipids, glucose, insulin, and resistin were measured. RESULTS: The z-BMI scores were similar among the groups (p = 0.344), and body fat percentage (BF%) was similar among CPPT, CPPoT and prepubertal girls (p = 0.151). Resistin and insulin levels were lower in girls with CPP (CPPT and CPPoT) than in prepubertal and pubertal girls (median resistin level: CPPT 11.8 pg/ml vs CPPoT 11 pg/ml vs prepubertal 16 pg/ml vs pubertal 16 pg/ml, p = 0.001; median insulin level: CPPT 10.7 µUI/mL vs CPPoT 10.2 µUI/mL vs prepubertal 14.4 µUI/mL vs pubertal 32 µUI/mL p = 0.02). ANCOVA analysis, after adjustments for pubertal stage, BF% and z-BMI, showed that CPP modifies resistin levels (F = 31.4; p = 0.0001) independently of these parameters (p < 0.05). CONCLUSIONS: In the group of girls with overweight or obesity, the resistin level was lower in girls with CPP than in prepubertal and pubertal girls. More studies are needed to understand the role of resistin in CPP patients.