Thyrotropin-Releasing Hormone and Food Intake in Mammals: An Update.

Thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2) is an intercellular signal produced mainly by neurons. Among the multiple pharmacological effects of TRH, that on food intake is not well understood. We review studies demonstrating that peripheral injection of TRH generally produces a transient anorexic effect, discuss the pathways that might initiate this effect, and explain its short half-life. In addition, central administration of TRH can produce anorexic or orexigenic effects, depending on the site of injection, that are likely due to interaction with TRH receptor 1. Anorexic effects are most notable when TRH is injected into the hypothalamus and the nucleus accumbens, while the orexigenic effect has only been detected by injection into the brain stem. Functional evidence points to TRH neurons that are prime candidate vectors for TRH action on food intake. These include the caudal raphe nuclei projecting to the dorsal motor nucleus of the vagus, and possibly TRH neurons from the tuberal lateral hypothalamus projecting to the tuberomammillary nuclei. For other TRH neurons, the anatomical or physiological context and impact of TRH in each synaptic domain are still poorly understood. The manipulation of TRH expression in well-defined neuron types will facilitate the discovery of its role in food intake control in each anatomical scene.

Maternal history of maltreatment and offspring's emotional and behavioral problems in adolescence: Do family factors contribute to the intergenerational risk transmission?

BACKGROUND: A history of childhood maltreatment often has a negative and long-lasting impact across different domains in life. A childhood maltreatment experience in parents may even affect the next generation. So far, the effects of family factors have been considered in the intergenerational transmission of adversity across the childhood years, but whether the effects remain until adolescence is less clear. OBJECTIVE: Using data from a large population-based study in the Netherlands, including both mother and child reports, we examined whether maternal childhood maltreatment history is associated with increased mental health problems in offspring and the role of family functioning and harsh parenting as a potential pathway. PARTICIPANTS: 4912 adolescents (aged 13 years) and their mothers were recruited in the Generation R study. METHODS: Mothers reported childhood maltreatment experiences using the Childhood Trauma Questionnaire (CTQ), and adolescents reported on their mental health using the Youth Self Report (YSR). Structural equation modeling (SEM) was used to test the association of maternal childhood maltreatment on mental health problems in offspring and family functioning and harsh parenting as mechanisms to explain this association. RESULTS: Adolescents of mothers with a history of maltreatment had greater internalizing (ß = 0.07, p < .01) and externalizing problems (ß = 0.08, p < .01). Moreover, we found an indirect effect via family functioning over time and harsh parenting at ages 3 and 8 years which mediated this association. CONCLUSION: We concluded an intergenerational effect of maternal childhood maltreatment on adolescents internalizing and externalizing problems. The findings might enable earlier intervention within the family context to mitigate the consequences of maternal childhood maltreatment.

Inadequate diabetes knowledge is associated with poor glycemia control in patients with type 2 diabetes / El conocimiento inadecuado de la diabetes se asocia con un control glucémico deficiente en pacientes con diabetes de tipo 2

Objective: To identify the association between glycemia control with level of diabetes knowledge, diabetes education, and lifestyle variables in patients with type 2 diabetes. Design: Cross-sectional analytical study. Site: Clinics of the Mexican Institute of Social Security (IMSS), Mexico. Participants: Patients with type 2 diabetes. Main measurements: Glycated hemoglobin (HbA1c), glucose, and lipid profile levels were measured from fasting venous blood samples. Assessment of disease knowledge was performed using the Diabetes Knowledge Questionnaire (DKQ-24). Systolic and diastolic blood pressure was measured. Weight and abdominal circumference were measured, as well as body composition using bioimpedance. Sociodemographic, clinical, and lifestyle variables were obtained. Results: A total of 297 patients were included, sixty-seven percent (67%) were women with a median of six years since the diagnosis of diabetes. Only 7% of patients had adequate diabetes knowledge, and 56% had regular knowledge. Patients with adequate diabetes knowledge had a lower body mass index (p=0.016), lower percentage of fat (p=0.008), and lower fat mass (p=0.018); followed a diet (p=0.004) and had received diabetes education (p=0.002), and to obtain information about their illness (p=0.001). Patients with low levels of diabetes knowledge had a higher risk of HbA1c≥7% (OR: 4.68; 95% CI: 1.48,14.86; p=0.009), as well as those who did not receive diabetes education (OR: 2.17; 95% CI: 1.21–3.90; p=0.009) and those who did not follow a diet (OR: 2.37; 95% CI: 1.01,5.55; p=0.046). Conclusion: Inadequate knowledge of diabetes, lack of diabetes education, and dietary adherence are associated with poor glycemia control in patients with diabetes.(AU)

Objetivo: Identificar la asociación entre el control de la glicemia con el nivel de conocimiento, la educación y las variables de estilo de vida en pacientes con diabetes tipo 2. Diseño: Estudio transversal analítico. Sitio: Clínicas del Instituto Mexicano del Seguro Social, México. Participantes: Pacientes con diabetes tipo 2. Medidas principales: Se midió el nivel de hemoglobina glicosilada (HbA1c), glucosa y perfil de lípidos en ayuno. La evaluación del conocimiento de la enfermedad se realizó con el Cuestionario de Conocimiento de la Diabetes (DKQ-24). Se midió presión arterial, peso y circunferencia abdominal, así como la composición corporal con bioimpedancia. Las variables clínicas y de estilo de vida fueron registradas. Resultados: Se incluyó a 297 participantes y 67% fueron mujeres, con una mediana de diagnóstico de diabetes de seis años. Solo 7% tuvo un conocimiento adecuado de la diabetes y 56% un conocimiento regular. Los pacientes con conocimiento adecuado de la diabetes tuvieron un índice de masa corporal más bajo (p = 0,016), seguían una dieta (p = 0,004), recibieron educación en diabetes (p = 0,002), y obtuvieron información de su enfermedad (p = 0,001). Los pacientes con bajo nivel de conocimiento tuvieron mayor riesgo de HbA1c ≥ 7% (OR: 4,68; IC 95%: 1,48-14,86; p = 0,009), así como aquellos sin educación en diabetes (OR: 2,17; IC 95%: 1,21-3,90; p = 0,009) y quienes no seguían una dieta (OR: 2,37; IC 95%: 1,01-5,55; p = 0,046). Conclusión. El conocimiento inadecuado de diabetes, la falta de educación en diabetes y adherencia a la dieta se asocian a un control glucémico deficiente en pacientes con diabetes.(AU)

Prevalence of type 2 diabetes mellitus in the pediatric population of a third-level care hospital in Mexico City in 2013 and 2018.

BACKGROUND: Diabetes mellitus type 2 (T2DM) is a state of hyperglycemia due to a defect in the secretion and/or action of insulin, and it represents the most common form of diabetes worldwide. In Mexico, 10.3% of the adult population have been diagnosed with T2DM and it is expanding to the pediatric population. AIM: To evaluate and compare the prevalence of T2DM in the pediatric population at the Children's Hospital, "Hospital Infantil de México Federico Gómez (HIMFG)", at two time periods: 2013 vs 2018. METHODS: A comparison of two cross-sectional studies was done (2013 and 2018). The study population was comprised of children and adolescents 8-17 years old, from the Diabetes Clinic at the aforementioned institution. A comprehensive interrogation regarding family history and perinatal antecedents was performed. Complete blood work after 12 h of fasting was obtained to determine serum levels of glucose, glycated hemoglobin, lipid profile, C-peptide, and insulin. The data were analysed using the statistical software package SPSS v. 23.0. A P value of < 0.05 was considered statistically significant. RESULTS: A total of 151 patients were included: 47 from 2013, and 104 from 2018. There were age differences noted between the two periods with younger patients presenting T2DM in 2013. Also, T2DM predominated in the male sex in 55.36% in 2013 vs 32.7% in 2018. An increased prevalence of T2DM was noted from 2013 to 2018 (20.2% vs 33.0%, respectively), which was a statistically significant 12.8% increase (P < 0.0001). The illness phenotype was more aggressive in the 2018 group with the presence of a higher proportion of obesity, insulin resistance, and adverse lipid profiles. CONCLUSION: The prevalence of T2DM at the HIMFG institution from 2013 to 2018 increased by 12.8% (20.2% vs 33.0%, respectively). The study results demonstrate the need for vigilance in T2DM trends, and to strengthen programs of healthy nutrition and physical activity as well as early detection and risk factors for obesity, data on insulin resistance, and metabolic syndrome, with the aim of preventing the development of T2DM.

Inadequate diabetes knowledge is associated with poor glycemia control in patients with type 2 diabetes.

OBJECTIVE: To identify the association between glycemia control with level of diabetes knowledge, diabetes education, and lifestyle variables in patients with type 2 diabetes. DESIGN: Cross-sectional analytical study. SITE: Clinics of the Mexican Institute of Social Security (IMSS), Mexico. PARTICIPANTS: Patients with type 2 diabetes. MAIN MEASUREMENTS: Glycated hemoglobin (HbA1c), glucose, and lipid profile levels were measured from fasting venous blood samples. Assessment of disease knowledge was performed using the Diabetes Knowledge Questionnaire (DKQ-24). Systolic and diastolic blood pressure was measured. Weight and abdominal circumference were measured, as well as body composition using bioimpedance. Sociodemographic, clinical, and lifestyle variables were obtained. RESULTS: A total of 297 patients were included, sixty-seven percent (67%) were women with a median of six years since the diagnosis of diabetes. Only 7% of patients had adequate diabetes knowledge, and 56% had regular knowledge. Patients with adequate diabetes knowledge had a lower body mass index (p=0.016), lower percentage of fat (p=0.008), and lower fat mass (p=0.018); followed a diet (p=0.004) and had received diabetes education (p=0.002), and to obtain information about their illness (p=0.001). Patients with low levels of diabetes knowledge had a higher risk of HbA1c≥7% (OR: 4.68; 95% CI: 1.48,14.86; p=0.009), as well as those who did not receive diabetes education (OR: 2.17; 95% CI: 1.21-3.90; p=0.009) and those who did not follow a diet (OR: 2.37; 95% CI: 1.01,5.55; p=0.046). CONCLUSION: Inadequate knowledge of diabetes, lack of diabetes education, and dietary adherence are associated with poor glycemia control in patients with diabetes.

Propiedades Psicométricas de la Escala de Evaluación Socioemocional Breve de Infantes y Niños (BITSEA) en una muestra de niños y niñas chilenos / Psychometric properties of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) in a sample of Chilean children

Introducción: La infancia temprana es una etapa crítica para la salud mental, por lo que es fundamental contar con herramientas eficaces para detectar tempranamente conductas infantiles relacionadas con psicopatología. Objetivo: Investigar las propiedades psicométricas de la Escala de Evaluación Socioemocional Breve de Infantes y Niños (BITSEA) en una muestra de infantes chilenos. Método: 289 padres de niños y niñas de entre 12 y 36 meses de edad completaron la BITSEA y el CBCL 1½-5. Resultados: Se encontró una confiabilidad aceptable para las puntuaciones de la subescala "problema socioemocional" (ω=0.84), y una confiabilidad baja para las puntuaciones de la subescala "competencia socioemocional" (ω=0.59). La estructura factorial fue adecuada y se observó una alta validez concurrente con otras escalas. El modelo confirmatorio mostró índices aceptables (CFI= 0.94; TLI= 0.94; SRMR= 0.07; RMSEA= 0.027). Conclusión: La BITSEA en esta muestra arrojó resultados similares a otros estudios, su aplicabilidad es prometedora para la detección temprana de problema socioemocional en la infancia temprana. Se sugiere continuar su estudio en muestra nacional representativa.

Introduction: Early childhood is a critical stage for mental health, and it is necessary to have effective tools for early detection of child behaviours related to psychopathology. Objective: to assess the psychometric properties of the Brief Infant and Toddler Social-Emotional Evaluation Scale (BITSEA) in a sample of Chilean children. Methods: 289 parents of infants and toddlers aged 12-36 months completed the BITSEA and the CBCL 1½-5. Results: Acceptable reliability was found for the "socioemotional problems" dimension (ω=0.84), and low reliability for the "socioemotional competence" subscale scores (ω=0.59). The factor structure was adequate and high concurrent validity with other scales was observed. The confirmatory model showed acceptable fit indices (CFI= 0.94; TLI= 0.94; SRMR= 0.07; RMSEA= 0.027). Conclusion: The BITSEA in this sample showed similar results to other studies, its applicability is promising for the early detection of socioemotional problems in early childhood. It is suggested to continue its study in a nationally representative sample.

Maternal sensitivity in early childhood and body mass index in adolescence: A population-based study on the role of self-regulation as a mediator.

Maternal sensitivity has been implicated in various aspects of child health and development, including overweight. However, long-term effects, the role of paternal sensitivity and the explanatory pathways are unclear. This study examined whether maternal sensitivity in early childhood is prospectively associated with adolescent body mass index and whether children's self-regulation mediates this relation. Data from 540 children and their mothers were available from a large cohort study in the Netherlands. Maternal sensitivity was assessed at child ages 1, 3, and at 4 years paternal sensitivity was also included. Children's self-regulation skills were observed at age 3, eating behaviour was assessed at 10 years, and child BMI was measured at 13 years. Longitudinal structural equation modelling was applied. The cross-sectional association between maternal sensitivity and child self-regulation was significant, while lower levels of self-regulation and higher levels of food responsiveness and restrained eating predicted a higher child BMI at 13 years. Furthermore, a direct association of paternal sensitivity at 4 years with BMI at 13 years was found, but only in girls. Maternal sensitivity was not directly associated with child BMI after adjusting for covariates. Our findings showed the importance of self-regulation in the early years for subsequent weight development. Nevertheless, as self-regulation could not explain the relationship between parenting and child weight, research should focus on the contribution of other contextual factors, such as feeding styles and the social environment, to this relationship.

Sex-dependent and -independent regulation of thyrotropin-releasing hormone expression in the hypothalamic dorsomedial nucleus by negative energy balance, exercise, and chronic stress.

The dorsomedial nucleus of the hypothalamus (DMH) is part of the brain circuits that modulate organism responses to the circadian cycle, energy balance, and psychological stress. A large group of thyrotropin-releasing hormone (Trh) neurons is localized in the DMH; they comprise about one third of the DMH neurons that project to the lateral hypothalamus area (LH). We tested their response to various paradigms. In male Wistar rats, food restriction during adulthood, or chronic variable stress (CVS) during adolescence down-regulated adult DMH Trh mRNA levels compared to those in sedentary animals fed ad libitum; two weeks of voluntary wheel running during adulthood enhanced DMH Trh mRNA levels compared to pair-fed rats. Except for their magnitude, female responses to exercise were like those in male rats; in contrast, in female rats CVS did not change DMH Trh mRNA levels. A very strong negative correlation between DMH Trh mRNA levels and serum corticosterone concentration in rats of either sex was lost in CVS rats. CVS canceled the response to food restriction, but not that to exercise in either sex. TRH receptor 1 (Trhr) cells were numerous along the rostro-caudal extent of the medial LH. In either sex, fasting during adulthood reduced DMH Trh mRNA levels, and increased LH Trhr mRNA levels, suggesting fasting may inhibit the activity of TRHDMH->LH neurons. Thus, in Wistar rats DMH Trh mRNA levels are regulated by negative energy balance, exercise and chronic variable stress through sex-dependent and -independent pathways.

Diet and Maternal Obesity Are Associated with Increased Oxidative Stress in Newborns: A Cross-Sectional Study.

Overweight and obesity have become a world-health public problem, mainly for developing countries. Both health conditions have a higher prevalence among women of childbearing age. Physiopathology, overweight and obesity are characterized by a chronic oxidative stress status, which has deleterious effects on mothers and children. Hence, we determine whether the qualities of diet during pregnancy and maternal pregestational body mass index (BMI) are associated with increased oxidative stress markers in mothers and newborns. Two hundred forty-two (242) mother-newborn pairs were classified according to their pregestational BMI. Information on food intake was collected using a food frequency questionnaire in the third trimester of pregnancy. Levels of Malondialdehyde (MDA) and Nitric Oxide (NO) were measured in plasma from mothers at the end of the third trimester of pregnancy and from cord blood at birth. MDA and NO levels in mother-newborn pairs with maternal pregestational overweight or obesity were higher than in mother-newborn pairs with pregestational normal weight. For women (and newborns) who had a higher intake of fruit and vegetables, the levels of NO and MDA were lower. Lastly, women with pregestational obesity had lower fruit and vegetable intake during pregnancy and higher levels of oxidative stress and in their newborns.

Targeting the IspD Enzyme in the MEP Pathway: Identification of a Novel Fragment Class.

The enzymes of the 2-C-methylerythritol-d-erythritol 4-phosphate (MEP) pathway (MEP pathway or non-mevalonate pathway) are responsible for the synthesis of universal precursors of the large and structurally diverse family of isoprenoids. This pathway is absent in humans, but present in many pathogenic organisms and plants, making it an attractive source of drug targets. Here, we present a high-throughput screening approach that led to the discovery of a novel fragment hit active against the third enzyme of the MEP pathway, PfIspD. A systematic SAR investigation afforded a novel chemical structure with a balanced activity-stability profile (16). Using a homology model of PfIspD, we proposed a putative binding mode for our newly identified inhibitors that sets the stage for structure-guided optimization.

Sex Dimorphic Responses of the Hypothalamus-Pituitary-Thyroid Axis to Energy Demands and Stress.

The hypothalamus-pituitary-thyroid-axis (HPT) is one of the main neuroendocrine axes that control energy expenditure. The activity of hypophysiotropic thyrotropin releasing hormone (TRH) neurons is modulated by nutritional status, energy demands and stress, all of which are sex dependent. Sex dimorphism has been associated with sex steroids whose concentration vary along the life-span, but also to sex chromosomes that define not only sexual characteristics but the expression of relevant genes. In this review we describe sex differences in basal HPT axis activity and in its response to stress and to metabolic challenges in experimental animals at different stages of development, as well as some of the limited information available on humans. Literature review was accomplished by searching in Pubmed under the following words: "sex dimorphic" or "sex differences" or "female" or "women" and "thyrotropin" or "thyroid hormones" or "deiodinases" and "energy homeostasis" or "stress". The most representative articles were discussed, and to reduce the number of references, selected reviews were cited.

Sex Dimorphic Changes in Trh Gene Methylation and Thyroid-Axis Response to Energy Demands in Maternally Separated Rats.

The hypothalamus-pituitary-thyroid (HPT) axis regulates energy balance through the pleiotropic action of thyroid hormones. HPT basal activity and stimulation by cold or voluntary exercise are repressed by previous chronic stress in adults. Maternal separation (MS) modifies HPT basal activity; we thus studied the response of the axis to energy demands and analyzed possible epigenetic changes on Trh promoter. Nonhandled (NH) or MS male Wistar rats were cold exposed 1 h at adulthood; Trh expression in the hypothalamic paraventricular nucleus (PVN) and serum thyrotropin (TSH) concentration were increased only in NH rats. Two weeks of voluntary exercise decreased fat mass and increased Trh expression, and thyroid hormones concentration changed proportionally to running distance in NH male rats and MS male rats. Although NH females ran more than MS and much more than males, exercise decreased body weight and fat mass only in NH rats with no change on any parameter of the HPT axis but increased Pomc expression in arcuate-nucleus of NH and Npy in MS females. Overall, the methylation pattern of PVN Trh gene promoter was similar in NH males and females; MS modified methylation of specific CpG sites, a thyroid hormone receptor (THR)-binding site present after the initiation site was hypomethylated in MS males; in MS females, the THR binding site of the proximal promoter (site 4) and 2 sites in the first intron were hypermethylated. Our studies showed that, in a sex-dimorphic manner, MS blunted the responses of HPT axis to energy demands in adult animals and caused methylation changes on Trh promoter that could alter T3 feedback.

Evolution of thyrotropin-releasing factor extracellular communication units.

Thyroid hormones (THs) are ancient signaling molecules that contribute to the regulation of metabolism, energy homeostasis and growth. In vertebrates, the hypothalamus-pituitary-thyroid (HPT) axis links the corresponding organs through hormonal signals, including thyrotropin releasing factor (TRF), and thyroid stimulating hormone (TSH) that ultimately activates the synthesis and secretion of THs from the thyroid gland. Although this axis is conserved among most vertebrates, the identity of the hypothalamic TRF that positively regulates TSH synthesis and secretion varies. We review the evolution of the hypothalamic factors that induce TSH secretion, including thyrotropin-releasing hormone (TRH), corticotrophin-releasing hormone (CRH), urotensin-1-3, and sauvagine, and non-mammalian glucagon-like peptide in metazoans. Each of these peptides is part of an extracellular communication unit likely composed of at least 3 elements: the peptide, G-protein coupled receptor and bioavailability regulator, set up on the central neuroendocrine articulation. The bioavailability regulators include a TRH-specific ecto-peptidase, pyroglutamyl peptidase II, and a CRH-binding protein, that together with peptide secretion/transport rate and transduction coupling and efficiency at receptor level shape TRF signal intensity and duration. These vertebrate TRF communication units were coopted from bilaterian ancestors. The bona fide elements appeared early in chordates, and are either used alternatively, in parallel, or sequentially, in different vertebrate classes to control centrally the activity of the HPT axis. Available data also suggest coincidence between apparition of ligand and bioavailability regulator.

Using Exploratory Structural Equation Modeling (ESEM) to Examine the Internal Structure of Posttraumatic Stress Disorder Symptoms.

Several studies have reported the factor structure of posttraumatic stress disorder (PTSD) using confirmatory factor analysis (CFA). The results show models with different number of factors, high correlations between factors, and symptoms that belong to different factors in different models without affecting the fit index. These elements could suppose the existence of considerable item cross-loading, the overlap of different factors or even the presence of a general factor that explains the items common source of variance. The aim is to provide new evidence regarding the factor structure of PTSD using CFA and exploratory structural equation modeling (ESEM). In a sample of 1,372 undergraduate students, we tested six different models using CFA and two models using ESEM and ESEM bifactor analysis. Trauma event and past-month PTSD symptoms were assessed with Life Events Checklist for DSM-5 (LEC-5) and PTSD Checklist for DSM-5 (PCL-5). All six tested CFA models showed good fit indexes (RMSEA = .051-.056, CFI = .969-.977, TLI = .965-.970), with high correlations between factors (M = .77, SD = .09 to M = .80, SD = .09). The ESEM models showed good fit indexes (RMSEA = .027-.036, CFI = .991-.996, TLI = .985-.992). These models confirmed the presence of cross-loadings on several items as well as loads on a general factor that explained 76.3% of the common variance. The results showed that most of the items do not meet the assumption of dimensional exclusivity, showing the need to expand the analysis strategies to study the symptomatic organization of PTSD.

La educación con una plataforma multimedia en web mejora los conocimientos y la HbA1c de pacientes mexicanos con diabetes tipo 2. Ensayo clínico abierto / Education with a multimedia web platform improves knowledge and HbA1c of Mexican patients with type 2 diabetes. Open clinical trial

INTRODUCCIÓN: El paciente con diabetes mellitus tipo 2 requiere recibir educación acerca de la enfermedad dirigida a mejorar los conocimientos y habilidades para su control. El objetivo de este estudio fue evaluar la eficacia de la terapia nutricia y de la educación a través de un sitio multimedia, sobre el nivel de conocimientos y control metabólico en pacientes con diabetes tipo 2. MATERIAL Y MÉTODOS: Ensayo clínico abierto de 12 meses de seguimiento en 161 pacientes con diabetes tipo 2. Se asignaron 101 pacientes al grupo de intervención con terapia nutricional (TN) + Nutriluv (sitio multimedia), 80 pacientes al grupo control con TN. Se midió al inicio y al final la hemoglobina glucosilada (HbA1c), glucosa, colesterol, triglicéridos, colesterol LDL y HDL. Se registró el peso, la circunferencia de cintura, el porcentaje de grasa, la presión arterial sistólica y la diastólica. El nivel de conocimientos se midió con el cuestionario de conocimientos en diabetes DKQ24 (por sus siglas en inglés). RESULTADOS: Los conocimientos en diabetes mejoraron en el grupo con TN+Nutriluv comparado con el grupo TN (p < 0,05). La HbA1c, HDL, presión arterial diastólica y circunferencia de cintura mejoraron en el grupo con TN+Nutriluv (p < 0,05). En el grupo con TN mejoró el colesterol HDL, la presión arterial diastólica, la circunferencia de cintura y se incrementó el porcentaje de grasa (p < 0,05). Presentaron mayor riesgo de una HbA1c > 7% quienes tuvieron más años de diagnóstico de la diabetes. CONCLUSIÓN: El uso de un sitio multimedia para proveer educación en diabetes mejora los conocimientos, el HbA1c y otros indicadores de riesgo cardiovascular en pacientes con diabetes tipo 2

INTRODUCTION: The patient with diabetes mellitus type requires to receive education about the disease aimed at improving knowledge and skills for their control. The objective of this study is to evaluate the efficacy of nutritional therapy and education through a multimedia site on the level of knowledge and metabolic control in patients with type 2 diabetes. PATIENTS AND METHODS: Open-label clinical trial of 12 months of follow-up in 161 patients with type 2 diabetes. A total of 101 patients were assigned to the intervention group with nutrition therapy (TN) + Nutriluv (multimedia site in diabetes), 80 patients to the TN control group. The glycosylated hemoglobin (HbA1c), glucose, cholesterol, triglycerides, LDL and HDL cholesterol were measured at the beginning and end. Weight, waist circumference, percentage of fat, systolic blood pressure and diastolic blood pressure were recorded. The level of knowledge was measured with the Diabetes Knowledge Questionnaire (DKQ24). RESULTS: The knowledge in diabetes improved in the group with TN+Nutriluv compared with the TN group (P<0.05). HbA1c, HDL, diastolic blood pressure and waist circumference, improved in the group with TN+Nutriluv (P<0.05). In the group with TN, cholesterol HDL, diastolic blood pressure, waist circumference and the fat percentage was increased (P<0.05). They had a higher risk of having an HbA1c>7% who had more years of diagnosis of diabetes. CONCLUSIONS: The use of a multimedia site with education in diabetes, improves knowledge, HbA1c, and other indicators of cardiovascular risk in diabetes type 2 patients

Effects of fatty liver on the size and composition of high-density lipoprotein cholesterol subpopulations in adolescents with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an emerging disease in the pediatric population. The association between T2DM and non-alcoholic fatty liver disease (NAFLD) has been described. Recent evidence suggests that sizes and composition of high-density lipoprotein (HDL) may be more important that HDL-C levels in predicting coronary heart disease. There is not data regarding the HDL subclasses distribution and composition in T2DM youths with NAFLD. METHODS: This cross-sectional study included 47 adolescents with T2DM and 23 non-diabetic controls of both sexes aged 10 to 18 years. The presence of NAFLD was determined estimated proton density fat fraction (PDFF) by magnetic resonance by spectroscopy. We compared the HDL subclasses distribution (HDL2b, HDL2a, HDL3a HDL3b and HDL3c) and the HDL chemical composition (total protein, triglyceride, phospholipid, cholesteryl esters, and free cholesterol) between the groups of adolescents with T2DM and the control group. RESULTS: Patients with T2DM and NAFLD had a significantly lower proportion HDL2b (P = .040) and a higher proportion of HDL3c (P = .035); higher proportion of TG (P = .032) and a lower CE (P = .002) and FC (P < .001). A negative association was observed between PDFF and the percentages of HDL2b (r2 = -0.341, P = .004) and the average particle size (r2 = -0.327, P = .05), and a positive association with HDL3c subpopulations (r2 = 0.327, P = .015); about composition inside HDL particle, a positive association with PDFF and the TG (r2 = 0.299, P = .013) and negative with CE (r2 = -0.265, P = .030). CONCLUSIONS: In adolescents diagnosed with T2DM, the presence of NAFLD is associated with abnormalities in the distribution of HDL subpopulations and the lipid composition of HDL particles.

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.

Growth hormone ameliorates high glucose-induced steatosis on in vitro cultured human HepG2 hepatocytes by inhibiting de novo lipogenesis via ChREBP and FAS suppression.

OBJECTIVE: Growth hormone (GH) deficiency has been associated with increased steatosis but the molecular mechanism has not been fully elucidated. We investigated the effect of GH on lipid accumulation of HepG2 cells cultured on an in vitro steatosis model and examined the potential involvement of insulin-like growth factor 1 (IGF-1) as well as lipogenic and lipolytic molecules. METHODS: Control and steatosis conditions were induced by culturing HepG2 cells with 5.5 or 25 mmol/l glucose for 24 h, respectively. Afterward, cells were exposed to 0, 5, 10 or 20 ng/ml GH for another 24 h. Lipid content was quantified as well as mRNA and protein levels of IGF-1, carbohydrate responsive element-binding protein (ChREBP), sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyltransferase 1A (CPT1A), and peroxisome proliferator-activated receptor alpha (PPAR-alpha) by qPCR and western blot, respectively. Data were analyzed by one-way ANOVA and the Games-Howell post-hoc test. RESULTS: In the steatosis model, HepG2 hepatocytes showed a significant 2-fold increase in lipid amount as compared to control cells. IGF-1 mRNA and protein levels were significantly increased in control cells exposed to 10 ng/ml GH, whereas high glucose abolished this effect. High glucose also significantly increased both mRNA and protein of ChREBP and FAS without having effect on SREBP1c, CPT1A and PPAR-alpha. However, GH inhibited ChREBP and FAS production, even in HepG2 hepatocytes cultured under steatosis conditions. CONCLUSIONS: Growth hormone ameliorates high glucose-induced steatosis in HepG2 cells by suppressing de novo lipogenesis via ChREBP and FAS down-regulation.

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.