Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. METHODS: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. DISCUSSION: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].

GrimAge is elevated in older adults with mild COVID-19 an exploratory analysis.

COVID-19 has been contained; however, the side effects associated with its infection continue to be a challenge for public health, particularly for older adults. On the other hand, epigenetic status contributes to the inter-individual health status and is associated with COVID-19 severity. Nevertheless, current studies focus only on severe COVID-19. Considering that most of the worldwide population developed mild COVID-19 infection. In the present exploratory study, we aim to analyze the association of mild COVID-19 with epigenetic ages (HorvathAge, HannumAge, GrimAge, PhenoAge, SkinAge, and DNAmTL) and clinical variables obtained from a Mexican cohort of older adults. We found that all epigenetic ages significantly differ from the chronological age, but only GrimAge is elevated. Additionally, both the intrinsic epigenetic age acceleration (IEAA) and the extrinsic epigenetic age acceleration (EEAA) are accelerated in all patients. Moreover, we found that immunological estimators and DNA damage were associated with PhenoAge, SkinBloodHorvathAge, and HorvathAge, suggesting that the effects of mild COVID-19 on the epigenetic clocks are mainly associated with inflammation and immunology changes. In conclusion, our results show that the effects of mild COVID-19 on the epigenetic clock are mainly associated with the immune system and an increase in GrimAge, IEAA, and EEAA.

[From genotype to phenotype: amylase gene in childhood obesity]. / Del genotipo al fenotipo: gen de la amilasa en obesidad infantil.

Worldwide, Mexico is one of the countries with the highest rate of obesity, which is a condition considered the main risk factor for type 2 diabetes. Among the mechanisms that predispose to obesity, the interaction between food intake and genetic components has been little explored. Recently we evidenced a significant association between the copy number (CN) of AMY1A and AMY2A genes, the enzymatic activity of salivary and pancreatic amylase, and the frequency of childhood obesity in Mexico, a particular population due to the high consumption of starch in the diet and the high prevalence of obesity in children and adults. This review aims to find a better understanding of the role of amylase in obesity through a description of the evolution of the CN of its genes, the association of its enzymatic activity with obesity, and the effect of its interaction with starch intake on Mexican children. In addition, it denotes the importance of the experimental perspectives of further investigation regarding the mechanism by which amylase could regulate the abundance of oligosaccharide-fermenting bacteria and producers of short-chain fatty acids and/or branched-chain amino acids that could contribute to the alteration of the physiological processes associated with intestinal inflammation and metabolic deregulation that predispose to the development of obesity.

A nivel mundial, México es uno de los países con la tasa más alta de obesidad, un padecimiento considerado como el principal factor de riesgo de diabetes tipo 2. Dentro de los mecanismos que predisponen a la obesidad, la interacción entre la ingesta alimentaria y el componente genético ha sido poco explorada. Recientemente evidenciamos la asociación del número de copias (NC) de los genes AMY1A y AMY2A, y la actividad enzimática de amilasa salival y pancreática con la frecuencia de obesidad infantil en México, una población que se caracteriza por presentar alto consumo de almidón en la dieta y alta prevalencia de obesidad. La presente revisión busca conseguir un mejor entendimiento del papel de la amilasa en la obesidad por medio de una descripción de la evolución del NC de sus genes, la asociación de su actividad enzimática con la obesidad y el efecto de su interacción con la ingesta de almidón en niños mexicanos. Además, refiere las perspectivas experimentales que permitirían profundizar en la investigación del mecanismo por el cual la amilasa podría regular la abundancia de bacterias fermentadoras de oligosacáridos y productoras de ácidos grasos de cadena corta o aminoácidos de cadena ramificada que podrían contribuir con la alteración de los procesos fisiológicos asociados con la inflamación intestinal y la desregulación metabólica que predispone al desarrollo de obesidad.

[Activation of endoplasmic reticulum stress sensors by metabolic disease-associated diets and COVID-19]. / Activación de sensores del estrés del retículo endoplásmico por dietas asociadas a enfermedades metabólicas y COVID-19.

The endoplasmic reticulum is an abundant, dynamic and energy-sensing organelle. Its abundant membranes, rough and smooth, are distributed in different proportions depending on the cell lineage and requirement. Its function is to carry out protein and lipid synthesis, and it is the main intracellular Ca2+ store. Caloric overload and glycolipotoxicity generated by hypercaloric diets cause alteration of the endoplasmic reticulum, activating the Unfolded Protein Response (UPR) as a reaction to cellular stress related to the endoplasmic reticulum and whose objective is to restore the homeostasis of the organelle by decreasing oxidative stress, protein synthesis and Ca2+ leakage. However, during chronic stress, the UPR induces reactive oxygen species formation, inflammation and apoptosis, exacerbating the state of the endoplasmic reticulum and propagating a deleterious effect on the other organelles. This is why endoplasmic reticulum stress has been considered an inducer of the onset and development of metabolic diseases, including the aggravation of COVID-19. So far, few strategies exist to reestablish endoplasmic reticulum homeostasis, which are targeted to sensors that trigger UPR. Therefore, the identification of new mechanisms and novel therapies related to mitigating the impact of endoplasmic reticulum stress and associated complications is urgently warranted.

El retículo endoplásmico es un organelo abundante, dinámico y sensor de energía. Sus abundantes membranas, rugosa y lisa, se encuentran distribuidas en diferentes proporciones dependiendo del linaje y requerimiento celular. Su función es llevar a cabo la síntesis de proteínas y lípidos, y es el almacén principal de Ca2+ intracelular. La sobrecarga calórica y la glucolipotoxicidad generada por dietas hipercalóricas provoca la alteración del retículo endoplásmico, activando la respuesta a proteínas mal plegadas (UPR, Unfolded Protein Response, por sus siglas en inglés) como reacción al estrés celular relacionado con el retículo endoplásmico y cuyo objetivo es restablecer la homeostasis del organelo al disminuir el estrés oxidante, la síntesis de proteínas y la fuga de Ca2+. Sin embargo, durante un estrés crónico, la UPR induce formación de especies reactivas de oxígeno, inflamación y apoptosis, exacerbando el estado del retículo endoplásmico y propagando un efecto nocivo para los demás organelos. Es por ello que el estrés del retículo endoplásmico se ha considerado un inductor del inicio y desarrollo de enfermedades metabólicas, incluido el agravamiento de COVID-19. Hasta el momento, existen pocas estrategias para reestablecer la homeostasis del retículo endoplásmico, las cuales son dirigidas a los sensores que desencadenan la UPR. Por tanto, se justifica con urgencia la identificación de nuevos mecanismos y terapias novedosas relacionadas con mitigar el impacto del estrés del retículo endoplásmico y las complicaciones asociadas.

Activación de sensores del estrés del retículo endoplásmico por dietas asociadas a enfermedades metabólicas y COVID-19 / Activation of endoplasmic reticulum stress sensors by metabolic disease-associated diets and COVID-19

El retículo endoplásmico es un organelo abundante, dinámico y sensor de energía. Sus abundantes membranas, rugosa y lisa, se encuentran distribuidas en diferentes proporciones dependiendo del linaje y requerimiento celular. Su función es llevar a cabo la síntesis de proteínas y lípidos, y es el almacén principal de Ca2+ intracelular. La sobrecarga calórica y la glucolipotoxicidad generada por dietas hipercalóricas provoca la alteración del retículo endoplásmico, activando la respuesta a proteínas mal plegadas (UPR, Unfolded Protein Response, por sus siglas en inglés) como reacción al estrés celular relacionado con el retículo endoplásmico y cuyo objetivo es restablecer la homeostasis del organelo al disminuir el estrés oxidante, la síntesis de proteínas y la fuga de Ca2+. Sin embargo, durante un estrés crónico, la UPR induce formación de especies reactivas de oxígeno, inflamación y apoptosis, exacerbando el estado del retículo endoplásmico y propagando un efecto nocivo para los demás organelos. Es por ello que el estrés del retículo endoplásmico se ha considerado un inductor del inicio y desarrollo de enfermedades metabólicas, incluido el agravamiento de COVID-19. Hasta el momento, existen pocas estrategias para reestablecer la homeostasis del retículo endoplásmico, las cuales son dirigidas a los sensores que desencadenan la UPR. Por tanto, se justifica con urgencia la identificación de nuevos mecanismos y terapias novedosas relacionadas con mitigar el impacto del estrés del retículo endoplásmico y las complicaciones asociadas.

The endoplasmic reticulum is an abundant, dynamic and energy-sensing organelle. Its abundant membranes, rough and smooth, are distributed in different proportions depending on the cell lineage and requirement. Its function is to carry out protein and lipid synthesis, and it is the main intracellular Ca2+ store. Caloric overload and glycolipotoxicity generated by hypercaloric diets cause alteration of the endoplasmic reticulum, activating the Unfolded Protein Response (UPR) as a reaction to cellular stress related to the endoplasmic reticulum and whose objective is to restore the homeostasis of the organelle by decreasing oxidative stress, protein synthesis and Ca2+ leakage. However, during chronic stress, the UPR induces reactive oxygen species formation, inflammation and apoptosis, exacerbating the state of the endoplasmic reticulum and propagating a deleterious effect on the other organelles. This is why endoplasmic reticulum stress has been considered an inducer of the onset and development of metabolic diseases, including the aggravation of COVID-19. So far, few strategies exist to reestablish endoplasmic reticulum homeostasis, which are targeted to sensors that trigger UPR. Therefore, the identif ication of new mechanisms and novel therapies related to mitigating the impact of endoplasmic reticulum stress and associated complications is urgently warranted.

[Scientific evidence of the consequences of modernity]. / La evidencia científica de las consecuencias de la modernidad.

The prevalence of type 2 diabetes (T2D) in Mexico is 14.4%. This disease is characterized by a state of hyperglycemia and chronic inflammation secondary to inadequate insulin secretion and its resistance. Among its risk factors for metabolic diseases development, the interaction between obesity, sedentary lifestyle, hypercaloric diets and genetic variants play an important role. For decades, different basic and applied research groups have worked in an interdisciplinary way to provide scientific evidence that has helped to understand the mechanisms involved in the pathophysiology of T2D in Mexicans. However, today the urgency of the advance and better proposals for prevention and management of patients with T2D makes it necessary to use translational medicine, which integrates scientific knowledge with the use of innovative technologies to provide comprehensive health care. In this sense, the present document concisely describes, with a translational approach, the implications of the interaction of environmental and genetic risk factors in the development of childhood obesity and T2D in Mexico.

La prevalencia de diabetes tipo 2 (DT2) en México es del 14.4%. La enfermedad se caracteriza por un estado de hiperglucemia e inflamación crónica secundaria a la resistencia y la secreción inadecuada de insulina. Dentro de sus factores de riesgo destacan la obesidad, el sedentarismo, las dietas hipercalóricas y las variantes genéticas. Durante décadas, diferentes grupos de investigación básica y aplicada han trabajado de forma interdisciplinaria para ofrecer evidencia científica que ha ayudado a entender los mecanismos implicados en la fisiopatología de la DT2 en pacientes mexicanos. Sin embargo, hoy en día la urgencia de conseguir mejores propuestas de prevención y manejo del paciente con DT2 hace necesario el uso de la medicina traslacional, que integra el conocimiento científico con el uso de tecnologías innovadoras para brindar una atención integral. El presente documento describe de forma concisa y con un enfoque traslacional las implicaciones de la interacción de factores de riesgo ambientales y genéticos en el desarrollo de obesidad infantil y DT2 en México.

La evidencia científica de las consecuencias de la modernidad / Scientific evidence of the consequences of modernity

Resumen La prevalencia de diabetes tipo 2 (DT2) en México es del 14.4%. La enfermedad se caracteriza por un estado de hiperglucemia e inflamación crónica secundaria a la resistencia y la secreción inadecuada de insulina. Dentro de sus factores de riesgo destacan la obesidad, el sedentarismo, las dietas hipercalóricas y las variantes genéticas. Durante décadas, diferentes grupos de investigación básica y aplicada han trabajado de forma interdisciplinaria para ofrecer evidencia científica que ha ayudado a entender los mecanismos implicados en la fisiopatología de la DT2 en pacientes mexicanos. Sin embargo, hoy en día la urgencia de conseguir mejores propuestas de prevención y manejo del paciente con DT2 hace necesario el uso de la medicina traslacional, que integra el conocimiento científico con el uso de tecnologías innovadoras para brindar una atención integral. El presente documento describe de forma concisa y con un enfoque traslacional las implicaciones de la interacción de factores de riesgo ambientales y genéticos en el desarrollo de obesidad infantil y DT2 en México.

Abstract The prevalence of type 2 diabetes (T2D) in Mexico is 14.4%. This disease is characterized by a state of hyperglycemia and chronic inflammation secondary to inadequate insulin secretion and its resistance. Among its risk factors for metabolic diseases development, the interaction between obesity, sedentary lifestyle, hypercaloric diets and genetic variants play an important role. For decades, different basic and applied research groups have worked in an interdisciplinary way to provide scientific evidence that has helped to understand the mechanisms involved in the pathophysiology of T2D in Mexicans. However, today the urgency of the advance and better proposals for prevention and management of patients with T2D makes it necessary to use translational medicine, which integrates scientific knowledge with the use of innovative technologies to provide comprehensive health care. In this sense, the present document concisely describes, with a translational approach, the implications of the interaction of environmental and genetic risk factors in the development of childhood obesity and T2D in Mexico.

Situación actual de la obesidad infantil en México / Childhood obesity: current situation in Mexico

México ha reportado en el año 2016 una prevalencia combinada de obesidad y sobrepeso del 33,2% en niños. El objetivo de este trabajo fue hacer una revisión bibliográfica de los factores asociados a la obesidad en niños mexicanos, como factores genéticos, patrones de alimentación, sedentarismo y microbiota intestinal. Se encontró que en niños mexicanos existe la presencia de SNP (single nucleotide polymorphism) en genes como MC4R, FTO y ADRB1, asociados a la obesidad, y que el polimorfismo PON1-192 incrementa el riesgo de padecer resistencia a la insulina. Por otro lado, la variante del gen ADIPOR2 (rs11061971) protege a los niños mexicanos contra la obesidad, al tiempo que un mayor número de copias del gen AMY fue encontrada en niños con peso normal. La evidencia del número de copias es de gran importancia, ya que la dieta actual del mexicano es rica en carbohidratos y grasas, origen de una transición nutricional que incluye actividades sedentarias y un alto consumo de bebidas azucaradas. El consumo de determinados alimentos provoca cambios importantes en la microbiota intestinal que contribuyen al desarrollo de la obesidad y la resistencia a la insulina. Se ha encontrado que niños mexicanos con obesidad presentan mayor abundancia de bacterias del phylum Firmicutes y de la especie B. eggerhii. Al ser tan diverso el tema de obesidad, es indispensable diversificar el tratamiento en el que se involucren autoridades gubernamentales, padres de familia e instancias sanitarias, así como reforzar temas de nutrición y alimentación saludable en la educación primaria del país para revertir las cifras y prevenir el desarrollo de otras patologías en los niños mexicanos

Mexico has reported in 2016 a combined prevalence of obesity and overweight of 33.2% in children. The objective of this work was to make a literature review of the factors associated with obesity in Mexican children, such as genetic factors, feeding patterns, sedentary lifestyle and gut microbiota. We found that in Mexican children SNP (single nucleotide polymorphism) is present in genes such as MC4R, FTO and ADRB1, associated with obesity, and that PON-1192 polymorphism increases the risk of suffering insulin resistance. On the other hand, the variant of the ADIPOR2 gene (rs11061971) protects Mexican children against obesity, as well as a greater number of copies of the AMY gene was found in children with normal weight. The evidence of the number of copies is very important, since the current diet of the Mexican population is rich in carbohydrates and fats, origin of a nutritional transition that includes sedentary activities and a high consumption of sugary drinks. The consumption of certain foods causes important changes in the gut microbiota that contribute to the development of obesity and insulin resistance. It has been found that Mexican children with obesity have a higher abundance of phylum Firmicutes and B. eggerhii bacteria. Therefore, as obesity is so diverse, it is essential to diversify the treatment in which government authorities, parents and health authorities should get involved, as well as reinforcing nutrition and healthy eating issues in primary education in the country in order to reverse the prevalence and prevent the development of other pathologies in Mexican children

Childhood obesity: current situation in Mexico. / Situación actual de la obesidad infantil en México

Introduction: Mexico has reported in 2016 a combined prevalence of obesity and overweight of 33.2% in children. The objective of this work was to make a literature review of the factors associated with obesity in Mexican children, such as genetic factors, feeding patterns, sedentary lifestyle and gut microbiota. We found that in Mexican children SNP (single nucleotide polymorphism) is present in genes such as MC4R, FTO and ADRB1, associated with obesity, and that PON-1192 polymorphism increases the risk of suffering insulin resistance. On the other hand, the variant of the ADIPOR2 gene (rs11061971) protects Mexican children against obesity, as well as a greater number of copies of the AMY gene was found in children with normal weight. The evidence of the number of copies is very important, since the current diet of the Mexican population is rich in carbohydrates and fats, origin of a nutritional transition that includes sedentary activities and a high consumption of sugary drinks. The consumption of certain foods causes important changes in the gut microbiota that contribute to the development of obesity and insulin resistance. It has been found that Mexican children with obesity have a higher abundance of phylum Firmicutes and B. eggerhii bacteria. Therefore, as obesity is so diverse, it is essential to diversify the treatment in which government authorities, parents and health authorities should get involved, as well as reinforcing nutrition and healthy eating issues in primary education in the country in order to reverse the prevalence and prevent the development of other pathologies in Mexican children.

Introducción: México ha reportado en el año 2016 una prevalencia combinada de obesidad y sobrepeso del 33,2% en niños. El objetivo de este trabajo fue hacer una revisión bibliográfica de los factores asociados a la obesidad en niños mexicanos, como factores genéticos, patrones de alimentación, sedentarismo y microbiota intestinal. Se encontró que en niños mexicanos existe la presencia de SNP (single nucleotide polymorphism) en genes como MC4R, FTO y ADRB1, asociados a la obesidad, y que el polimorfismo PON1-192 incrementa el riesgo de padecer resistencia a la insulina. Por otro lado, la variante del gen ADIPOR2 (rs11061971) protege a los niños mexicanos contra la obesidad, al tiempo que un mayor número de copias del gen AMY fue encontrada en niños con peso normal. La evidencia del número de copias es de gran importancia, ya que la dieta actual del mexicano es rica en carbohidratos y grasas, origen de una transición nutricional que incluye actividades sedentarias y un alto consumo de bebidas azucaradas. El consumo de determinados alimentos provoca cambios importantes en la microbiota intestinal que contribuyen al desarrollo de la obesidad y la resistencia a la insulina. Se ha encontrado que niños mexicanos con obesidad presentan mayor abundancia de bacterias del phylum Firmicutes y de la especie B. eggerhii. Al ser tan diverso el tema de obesidad, es indispensable diversificar el tratamiento en el que se involucren autoridades gubernamentales, padres de familia e instancias sanitarias, así como reforzar temas de nutrición y alimentación saludable en la educación primaria del país para revertir las cifras y prevenir el desarrollo de otras patologías en los niños mexicanos.

Molecular alterations induced by fructose and its impact on metabolic diseases / Alteraciones moleculares inducidas por fructosa y su impacto en las enfermedades metabólicas

Scientific evidence has identified that the excessive consumption of products made from high-fructose corn syrup is a trigger for obesity, whose prevalence increased in recent years. Due to the metabolic characteristics of fructose, a rapid gastric emptying is produced, altering signals of hunger-satiety and decreasing the appetite. In addition to the hepatic level during catabolism, triose phosphate is generated and adenosine triphosphate (ATP) is reduced, producing uric acid. Triose phosphate triggers the synthesis of fatty acids that increase the production and accumulation of triglycerides, diacylglycerols and ceramides that induce insulin resistance. Hyperlipidemia, insulin resistance and hyperuricemia contribute to the development of hypertension, cardiovascular disease, kidney failure, non-alcoholic fatty liver disease and some kinds of cancer. Understanding the molecular mechanisms and signaling pathways altered by the consumption of fructose is relevant to understand the development of metabolic diseases, as well as to seek therapeutic strategies to improve quality of life.

Las evidencias científicas identifican que el excesivo consumo de productos elaborados con jarabe de maíz de alta fructosa es el detonante de la obesidad, cuya prevalencia incrementó en los últimos años. Debido a las características metabólicas de la fructosa, se produce un rápido vaciado gástrico que altera las señales de hambre-saciedad y disminuye el apetito. A nivel hepático, durante su catabolismo se generan triosas fosfato y decrece el trifosfato de adenosina (ATP, por sus siglas en inglés), lo cual produce ácido úrico. Las triosas fosfato son dirigidas hacia la síntesis de ácidos grasos, incrementando la producción y la acumulación de triacilglicéridos, diacilglicerol y ceramidas que inducen resistencia a la insulina. La hiperlipidemia, la resistencia a la insulina y la hiperuricemia contribuyen al desarrollo de hipertensión, enfermedad cardiovascular, enfermedad renal crónica, hígado graso no alcohólico y algunos tipos de cáncer. Entender los mecanismos moleculares y las vías de señalización alteradas por el consumo de fructosa es relevante para comprender el desarrollo de enfermedades metabólicas, así como la búsqueda de estrategias terapéuticas para procurar una mejor calidad de vida.

Expression of candidate genes associated with obesity in peripheral white blood cells of Mexican children.

INTRODUCTION: Obesity is a chronic, complex, and multifactorial disease, characterized by excess body fat. Diverse studies of the human genome have led to the identification of susceptibility genes that contribute to obesity. However, relatively few studies have addressed specifically the association between the level of expression of these genes and obesity. MATERIAL AND METHODS: We studied 160 healthy and obese unrelated Mexican children aged 6 to 14 years. We measured the transcriptional expression of 20 genes associated with obesity, in addition to the biochemical parameters, in peripheral white blood cells. The detection of mRNA levels was performed using the OpenArray Real-Time PCR System (Applied Biosystems). RESULTS: Obese children exhibited higher values of fasting glucose (p = 0.034), fasting insulin (p = 0.004), low-density lipoprotein (p = 0.006), triglycerides (p < 0.001), systolic blood pressure and diastolic blood pressure (p < 0.001), and lower values of high-density lipoprotein (p < 0.001) compared to lean children. Analysis of transcriptional expression data showed a difference for ADRB1 (p = 0.0297), ADIPOR1 (p = 0.0317), GHRL (p = 0.0060) and FTO (p = 0.0348) genes. CONCLUSIONS: Our results suggest that changes in the expression level of the studied genes are involved in biological processes implicated in the development of childhood obesity. Our study contributes new perspectives for a better understanding of biological processes involved in obesity. The protocol was approved by the National Committee and Ethical Committee Board from the Mexican Social Security Institute (IMSS) (IMSS FIS/IMSS/PRIO/10/011).

Aterosclerosis placentaria y marcadores de disfunción endotelial en neonatos hijos de madres con diabetes gestacional / Placental atherosclerosis and markers of endothelial dysfunction in infants born to mothers with gestational diabetes

Antecedentes y objetivo: La fisiopatología de la diabetes gestacional provoca por sí misma una hiperestimulación del tejido adiposo y de las células placentarias que aumenta la producción de citocinas inflamatorias, las cuales provocan cambios en los tejidos expuestos como la placenta y el feto, por lo que en este estudio el objetivo fue comparar los marcadores metabólicos y de disfunción endotelial en sangre de cordón umbilical, así como determinar la presencia de aterosclerosis en las placentas de hijos neonatos de pacientes con diabetes gestacional y en pacientes con embarazo normoevolutivo. Pacientes y método: Se realizó un estudio transversal analítico en 84 pacientes, de las cuales se obtuvieron datos como edad, tabaquismo y ganancia de peso en el embarazo; del recién nacido se determinó la edad gestacional por Capurro, el peso y el destino posterior al nacimiento. Además se utilizaron las placentas para la búsqueda de aterosclerosis mediante estudio anatomopatológico y en las muestras sanguíneas obtenidas de cordón umbilical se determinaron glucosa, insulina, colesterol, c-VLDL, c-HDL, triglicéridos, fibrinógeno, PCR y los marcadores de disfunción endotelial (adiponectina, VCAM-1, ICAM-1 e IL-6). Resultados: La aterosclerosis placentaria se presentó en un 28,94% del grupo que cursó con diabetes gestacional frente a un 10,52% del grupo con embarazo normoevolutivo (p=0,044); se encontraron diferencias en glucosa, colesterol, triglicéridos, fibrinógeno, HOMA-IR, PCR-us y c-HDL, no encontrándose en c-VLDL. El 21,05% de los recién nacidos de las pacientes con diabetes gestacional requirieron hospitalización frente al 5,2% del grupo control. Conclusiones: Los embarazos que cursan con diabetes presentan una mayor proporción de aterosclerosis, de hospitalización en el recién nacido, de resistencia a la insulina, así como de elevación de marcadores relacionados con inflamación y disfunción endotelial en sangre de cordón umbilical (AU)

Background and objective: The pathophysiology of gestational diabetes itself causes hyperstimulation of adipose tissue and of the placenta cells increasing the production of inflammatory cytokines, which cause changes in the tissues exposed such as the placenta and foetus. Therefore, the objective of this study was to compare metabolic markers and endothelial dysfunction in umbilical cord blood, as well as to determine the presence of atherosclerosis in the placentas of newborn infants of patients with gestational diabetes and in patients with normally progressing pregnancies. Patients and method: An analytical cross-sectional study was carried out in 84 patients, obtaining data such as age, smoking and weight gain in pregnancy; the gestational age of the newborns was determined by Capurro, and their weight and destination subsequent to birth, the placentas were also collected in order to look for atherosclerosis through histological studies and glucose, insulin, VLDL-C, HDL-C, triglycerides, cholesterol, fibrinogen, PCR and markers of endothelial dysfunction (adiponectin, VCAM-1, ICAM-1 and IL-6) were determined in blood samples obtained from the umbilical cord. Results: Placental atherosclerosis presented in 28.94% of the group with gestational diabetes compared to 10.52% of the group with normally progressing pregnancies (P=.044); differences were found in glucose, cholesterol, triglycerides, fibrinogen, HOMA-IR, PCR-us, HDL-C, not in VLDL-C. Twenty-one point five percent of the newborns of the gestational diabetes patients required hospitalization, against 5.2% in the control group, Conclusions: Pregnancies that involve diabetes have higher proportion of atherosclerosis, hospitalization of the newborn, insulin resistance, as well as elevation of markers associated with inflammation and endothelial dysfunction in umbilical cord blood (AU)

[Placental atherosclerosis and markers of endothelial dysfunction in infants born to mothers with gestational diabetes]. / Aterosclerosis placentaria y marcadores de disfunción endotelial en neonatos hijos de madres con diabetes gestacional.

BACKGROUND AND OBJECTIVE: The pathophysiology of gestational diabetes itself causes hyperstimulation of adipose tissue and of the placenta cells increasing the production of inflammatory cytokines, which cause changes in the tissues exposed such as the placenta and foetus. Therefore, the objective of this study was to compare metabolic markers and endothelial dysfunction in umbilical cord blood, as well as to determine the presence of atherosclerosis in the placentas of newborn infants of patients with gestational diabetes and in patients with normally progressing pregnancies. PATIENTS AND METHOD: An analytical cross-sectional study was carried out in 84 patients, obtaining data such as age, smoking and weight gain in pregnancy; the gestational age of the newborns was determined by Capurro, and their weight and destination subsequent to birth, the placentas were also collected in order to look for atherosclerosis through histological studies and glucose, insulin, VLDL-C, HDL-C, triglycerides, cholesterol, fibrinogen, PCR and markers of endothelial dysfunction (adiponectin, VCAM-1, ICAM-1 and IL-6) were determined in blood samples obtained from the umbilical cord. RESULTS: Placental atherosclerosis presented in 28.94% of the group with gestational diabetes compared to 10.52% of the group with normally progressing pregnancies (P=.044); differences were found in glucose, cholesterol, triglycerides, fibrinogen, HOMA-IR, PCR-us, HDL-C, not in VLDL-C. Twenty-one point five percent of the newborns of the gestational diabetes patients required hospitalization, against 5.2% in the control group, CONCLUSIONS: Pregnancies that involve diabetes have higher proportion of atherosclerosis, hospitalization of the newborn, insulin resistance, as well as elevation of markers associated with inflammation and endothelial dysfunction in umbilical cord blood.

The interleukin-1ß-511 T>C (rs16944) gene polymorphism is associated with risk of developing silent myocardial ischemia in diabetic patients.

Silent myocardial ischemia (SMI) is a multifactorial and polygenic disorder that results from an excessive inflammatory response. Considering the prominent role of IL-1ß, IL-1F10 and IL-1RN as regulators of the inflammatory process and vascular physiology, the aim of the present study was to analyze whether IL-1ß, IL-1F10 and IL-1RN single nucleotide polymorphisms (SNPs) are associated with SMI. One polymorphism was associated with risk of SMI. Under co-dominant, recessive and additive models, the IL-1ß-511 T>C polymorphism was associated with increased risk of SMI when compared to healthy controls (OR=4.68, 95%CI=2.21-9.92, pCCo-dom=0.0048; OR=3.97, 95%CI=1.97-7.99, pCRec=0.0024; OR=2.02, 95%CI=1.41-2.90, pCAdd=0.0024, respectively). All models were adjusted for gender, age and smoking. Linkage disequilibrium analysis showed four haplotypes (CTCC, CCTC, CCCT and CTCC) with increased frequency in SMI patients when compared to healthy controls (OR=2.53, 95%CI=1.47-4.36, pC=0.0009, OR=2.34, 95%CI=1.15-4.74, pC=0.02, OR=2.44, 95%CI=1.14-5.18, pC=0.02, OR=5.11, 95%CI=1.37-19.05, pC=0.01, respectively). In summary, our data suggest that the IL-1ß-511 T>C polymorphism plays an important role in the development of SMI in diabetic patients. In addition, in our study was possible to distinguish one protective and four risk haplotypes for development of SMI.

[Genetics of pediatric obesity]. / Genética de la obesidad infantil.

Obesity is a major health problem around the globe. The statistics of overweight and obesity at early ages have reached alarming levels and placed our country in the first place in regard to childhood obesity. In the development of obesity two major factors take part, one genetic and the other one environmental. From the perspective of environmental changes both overweight and obesity result from the imbalance in the energy balance: people ingest more energy than they expend. Despite people live in the same obesogenic environment not all of them develop obesity; it requires genetic factors for this to happen. This review focuses on the description of the main methodologies to find genetic markers, as well as the main loci in candidate genes, whose single nucleotide polymorphisms (SNPs) are associated with obesity and its comorbidities in children, highlighting the association of these genes in the Mexican population. Knowledge of the genetic markers associated with obesity will help to understand the molecular and physiological mechanisms, the genetic background and changes in body mass index in the Mexican population. This information is useful for the planning of new hypotheses in the search for new biomarkers that can be used in a predictive and preventive way, as well as for the development of new therapeutic strategies.

La obesidad es uno de los principales problemas de salud a nivel mundial. Las cifras de sobrepeso y obesidad a edades tempranas han alcanzado niveles alarmantes y ubican a nuestro país en el primer lugar de obesidad infantil. En el desarrollo de la obesidad participan dos grandes factores, uno genético y otro ambiental. Desde la perspectiva de las alteraciones ambientales, tanto el sobrepeso como la obesidad resultan del desequilibrio en el balance energético: las personas ingieren mayor cantidad de energía de la que gastan. A pesar de que las personas vivan en el mismo ambiente obesógeno, no todos desarrollan obesidad; para que esto ocurra, se requiere de los factores genéticos. Esta revisión se enfoca en la descripción de las principales metodologías para la búsqueda de marcadores genéticos, así como los principales loci en genes candidatos, cuyos polimorfismos de un solo nucííleótido (SNP, por sus siglas en inglés) se encuentran asociados con la obesidad y sus comorbilidades en la población infantil, de lo cual resalta la asociación de estos genes en la población mexicana. El conocimiento de los marcadores genéticos asociados a la obesidad ayudará a comprender los mecanismos moleculares y fisiológicos, el fondo genético y las modificaciones en el índice de masa corporal en la población mexicana. Esta información es de gran utilidad para el planteamiento de nuevas hipótesis en la búsqueda de nuevos biomarcadores que puedan ser utilizados de una manera predictiva y preventiva, así como para el desarrollo de nuevas estrategias terapéuticas.

High expression of Toll-like receptors 2 and 9 and Th1/Th2 cytokines profile in obese asthmatic children.

Asthma is a common pulmonary disease with chronic inflammation of the airways, and obesity is a chronic state of low-grade inflammation. Toll-like receptors (TLRs) are involved in the innate immune response. This study was designed to analyze whether obesity has an effect on the immune response of patients with asthma. We included obese asthmatic, obese, asthmatic, and healthy children. Biochemical and anthropometric analyses were performed. Interleukin (IL)-2, interferon (IFN) gamma, IL-4, IL-10, IL-1beta, and tumor necrosis factor alpha were measured. Peripheral blood mononuclear cells were analyzed by immunostaining with anti-TLR2 and anti-TLR9 antibodies. The data were expressed as means ± SEM or medians and percentiles. Kruskal-Wallis test and Dunn's multiple comparison test were applied. Asthmatic patients, both obese and nonobese, exhibited a mild asthma phenotype; none had infectious process, exacerbation, or acute symptoms during the 30 days before the inclusion in the study. The IL-2 and IFN-gamma levels in the obese asthmatic group were lower than in the other three groups. IL-4 levels in the obese asthmatic group were almost equal to those of the asthmatic group and more than in the other two groups, without significant difference. There were higher levels of TLR2 and TLR9 in obese asthmatic patients than in the other three groups. There is a decrease in Th1 cytokines in obese asthmatic patients, and we only found a trend to an increased Th2 profile. Patients studied do not appear to fit into any of the endotypes described until now. This is the first study showing the high expression of TLR2 and TLR9 in obese asthmatic patients. It is necessary to study other cytokines in obese asthmatic patients to see if it is possible to fit them into any of the already described endotypes or if it is a distinct endotype.