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BACKGROUND: Adiposity favors several metabolic disorders with an exacerbated chronic pro-inflammatory status and tissue damage, with high levels of plasminogen activator inhibitor type 1 (PAI-1) and proprotein convertase subtilisin/kexin type 9 (PCSK9). OBJECTIVE: To demonstrate the influence of bariatric surgery on the crosstalk between PAI-1 and PCSK9 to regulate metabolic markers. METHODS: Observational and longitudinal study of 190 patients with obesity and obesity-related comorbidities who underwent bariatric surgery. We measured, before and after bariatric surgery, the anthropometric variables and we performed biochemical analysis by standard methods (glucose, insulin, triglycerides [TG], total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C] and TG/HDL-C ratio, PAI-1 and PCSK9 were measured by ELISA). RESULTS: PAI-1 levels decreased significantly after bariatric surgery, and were positively correlated with lipids, glucose, and TG, with significance on PCSK9 and TG/HDL-C alleviating the insulin resistance (IR) and inducing a state reversal of type 2 diabetes (T2D) with a significant decrease in body weight and BMI (p <0.0001). Multivariate regression analysis predicted a functional model in which PAI-1 acts as a regulator of PCSK9 (p <0.002), TG (p <0.05), and BMI; at the same time, PCSK9 modulates LDL-C HDL-C and PAI-1. CONCLUSIONS: After bariatric surgery, we found a positive association and crosstalk between PAI-1 and PCSK9, which modulates the delicate balance of cholesterol, favoring the decrease of circulating lipids, TG, and PAI-1, which influences the glucose levels with amelioration of IR and T2D, demonstrating the crosstalk between fibrinolysis and lipid metabolism, the two main factors involved in atherosclerosis and cardiovascular disease in human obesity.

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Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. Materials and Methods: We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild (n = 7), moderate (n = 19), or severe (n = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Results: The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group (p = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.008 and p = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group (p = 0.005 and p < 0.0001, respectively). Conclusions: In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.

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BACKGROUND: Pharmacological treatment with lipid-lowering and antihypertensive drugs has been proposed as a strategy to improve excess cardiovascular (CV) risk among obese individuals. The present study aimed to assess whether the CV polypill (Sincronium®) could be an effective strategy to help improve CV risk factor control in obese/overweight individuals requiring secondary prevention. METHODS: This was an observational, retrospective study reviewing the hospital medical records of 479 patients with established CV disease who initiated treatment with the CV polypill between 2013 and 2019 at a general hospital in Mexico. Patients were grouped as normal weight, overweight or obese according to their initial body mass index (BMI). We collected blood pressure (BP), lipid profile, and vascular age at the last visit recorded during the period following treatment. RESULTS: At the end of the study, all assessed lipid parameters improved compared to baseline regardless of the initial BMI category (all p<0.001). There was an increase from baseline regarding the proportion of patients with at target low-density lipoprotein cholesterol after treatment (2.3% vs. 30.1%; p<0.001), more than 80% of patients achieved triglyceride levels <200 mg/dL (p<0.001), and more than 80% achieved target BP levels in all BMI subgroups (p<0.001). The subanalyses in the elderly population yielded similar results, with a significant overall improvement in lipid and BP control after initiating the CV polypill strategy. CONCLUSIONS: The use of the CV polypill as baseline therapy for secondary prevention seems to be a reasonable strategy that enhances CV risk factor control regardless of the patient's BMI.

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The contribution of the cellular immune response to the severity of coronavirus disease 2019 (COVID-19) is still uncertain because most evidence comes from patients receiving multiple drugs able to change immune function. Herein, we conducted a prospective cohort study and obtained blood samples from 128 unvaccinated healthy volunteers to examine the in vitro response pattern of CD4+ and CD8+ T cells and monocyte subsets to polyclonal stimuli, including anti-CD3, anti-CD28, poly I:C, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) recombinant spike S1 protein, and lipopolysaccharide. Then, we started a six-month follow-up and registered 12 participants who got SARS-CoV-2 infection, from whom we retrospectively analyzed the basal immune response pattern of T cells and monocytes. Of the 12 participants infected, six participants developed mild COVID-19 with self-limiting symptoms such as fever, headache, and anosmia. Conversely, six other participants developed severe COVID-19 with pneumonia, respiratory distress, and hypoxia. Two severe COVID-19 cases required invasive mechanical ventilation. There were no differences between mild and severe cases for demographic, clinical, and biochemical baseline characteristics. In response to polyclonal stimuli, basal production of interleukin-2 (IL-2) and interferon (IFN-) gamma significantly decreased, and the programmed cell death protein 1 (PD-1) increased in CD4+ and CD8+ T cells from participants who posteriorly developed severe COVID-19 compared to mild cases. Likewise, CD14++CD16- classical and CD14+CD16+ non-classical monocytes lost their ability to produce IFN-alpha in response to polyclonal stimuli in participants who developed severe COVID-19 compared to mild cases. Of note, neither the total immunoglobulin G serum titers against the virus nor their neutralizing ability differed between mild and severe cases after a month of clinical recovery. In conclusion, using in vitro polyclonal stimuli, we found a basal immune response pattern associated with a predisposition to developing severe COVID-19, where high PD-1 expression and low IL-2 and IFN-gamma production in CD4+ and CD8+ T cells, and poor IFN-alpha expression in classical and non-classical monocytes are linked to disease worsening. Since antibody titers did not differ between mild and severe cases, these findings suggest cellular immunity may play a more crucial role than humoral immunity in preventing COVID-19 progression.

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Although in recent years in Mexico the quality of diabetes mellitus (DM) care has improved and access to health services and medications has increased, there is a lack of adherence to the recommendations of the clinical guidelines, which could explain the poor glycemic control in many of the patients with DM. Sodium-glucose cotransporter type 2 (iSGLT2) inhibitors have been the last class of antidiabetic agents to receive approval from the Food and Drug Administration (FDA) and COFEPRIS (Mexico). In order to improve the use of SGLT2i in clinical practice in Mexico, this paper presents the recommendations issued by a panel of eleven Mexican experts based on the new published evidence for the treatment of patients with DM2.

Aunque en los últimos años en México ha mejorado la calidad de la atención de la diabetes mellitus (DM) y ha aumentado el acceso a servicios de salud y medicamentos, existe una falta de apego a las recomendaciones de las guías de práctica clínica, que podría explicar la falta de un control glucémico adecuado en muchos de los pacientes con DM. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) han sido la última clase de agentes antidiabéticos en recibir la aprobación de la Food and Drug Administration (FDA) y de la Comisión Federal para la Protección contra Riesgos Sanitarios de México (COFEPRIS). Con el fin de mejorar el uso de los iSGLT2 en la práctica clínica en México, en este documento se presentan las recomendaciones emitidas por un panel de 11 expertos mexicanos con base en las nuevas evidencias publicadas para el tratamiento de los pacientes con DM2.

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Resumen Aunque en los últimos años en México ha mejorado la calidad de la atención de la diabetes mellitus (DM) y ha aumentado el acceso a servicios de salud y medicamentos, existe una falta de apego a las recomendaciones de las guías de práctica clínica, que podría explicar la falta de un control glucémico adecuado en muchos de los pacientes con DM. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) han sido la última clase de agentes antidiabéticos en recibir la aprobación de la Food and Drug Administration (FDA) y de la Comisión Federal para la Protección contra Riesgos Sanitarios de México (COFEPRIS). Con el fin de mejorar el uso de los iSGLT2 en la práctica clínica en México, en este documento se presentan las recomendaciones emitidas por un panel de 11 expertos mexicanos con base en las nuevas evidencias publicadas para el tratamiento de los pacientes con DM2.

Abstract Although in recent years in Mexico the quality of diabetes mellitus (DM) care has improved and access to health services and medications has increased, there is a lack of adherence to the recommendations of the clinical guidelines, which could explain the poor glycemic control in many of the patients with DM. Sodium-glucose cotransporter type 2 (iSGLT2) inhibitors have been the last class of antidiabetic agents to receive approval from the Food and Drug Administration (FDA) and COFEPRIS (Mexico). In order to improve the use of SGLT2i in clinical practice in Mexico, this paper presents the recommendations issued by a panel of eleven Mexican experts based on the new published evidence for the treatment of patients with DM2.

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There is a deep need for mortality predictors that allow clinicians to quickly triage patients with severe coronavirus disease 2019 (Covid-19) into intensive care units at the time of hospital admission. Thus, we examined the efficacy of the lymphocyte-to-neutrophil ratio (LNR) and neutrophil-to-monocyte ratio (NMR) as predictors of in-hospital death at admission in patients with severe Covid-19. A total of 54 Mexican adult patients with Covid-19 that met hospitalization criteria were retrospectively enrolled, followed-up daily until hospital discharge or death, and then assigned to survival or non-survival groups. Clinical, demographic, and laboratory parameters were recorded at admission. A total of 20 patients with severe Covid-19 died, and 75% of them were men older than 62.90 ± 14.18 years on average. Type 2 diabetes, hypertension, and coronary heart disease were more prevalent in non-survivors. As compared to survivors, LNR was significantly fourfold decreased while NMR was twofold increased. LNR ≤ 0.088 predicted in-hospital mortality with a sensitivity of 85.00% and a specificity of 74.19%. NMR ≥ 17.75 was a better independent risk factor for mortality with a sensitivity of 89.47% and a specificity of 80.00%. This study demonstrates for the first time that NMR and LNR are accurate predictors of in-hospital mortality at admission in patients with severe Covid-19.

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The discovery and synthesis of insulin has been vital in the study and treatment of diabetes mellitus. From the studies carried by Dr. Nicolae C. Paulescu in 1921 and descriptions of the pancrein, before those published by Banting and Macleod, the Nobel Prize winners in 1923, more metabolic and non-metabolic actions have been discovered and that are fundamental for life, growth and development of different organs and systems. Diverse studies in animal models have shown the participation in the development of the central nervous system, regeneration, neuronal apoptosis, and synaptic transmission, as well as the effects of its dysregulation in the pathophysiology of diseases such as dementia. Different researchers have demonstrated the synthesis of insulin at the brain, the mechanisms through which the blood-brain barrier crosses and how it regulates non-metabolic systems linked with the nueromodulation. This document to integrate these findings in the cerebral insulin circuit and the translation in clinical practice.

El descubrimiento y la síntesis de la insulina ha sido vitales en el estudio y el tratamiento de la diabetes mellitus. Desde los estudios realizados por el Dr. Nicolae C. Paulescu en 1921 y sus descripciones de la pancreína, antes de los publicados por Banting y Macleod, galardonados con el Premio Nobel en 1923, se han descubierto cada vez más acciones metabólicas y no metabólicas fundamentales para la vida, el crecimiento y el desarrollo de diferentes órganos y sistemas. En la actualidad, el estudio de esta hormona se nutre con más evidencia científica de su utilidad en blancos terapéuticos no metabólicos. Diversos estudios en modelos animales han demostrado su participación en el desarrollo del sistema nervioso central, la regeneración, la apoptosis neuronal y la transmisión sináptica, así como los efectos de su disregulación en la fisiopatología de enfermedades como la demencia. En la actualidad, diferentes investigadores han demostrado la síntesis de insulina en el cerebro, los mecanismos por los cuales atraviesa la barrera hematoencefálica y cómo regula sistemas no metabólicos ligados con la nueromodulación. Este documento trata de integrar estos hallazgos en un sistema insulinérgico cerebral y su posible traducción en la práctica clínica.

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Metabolic Syndrome (MetS) is a cluster of risk factors that, taken alone or synergically, are independent predictors of type 2 diabetes and cardiovascular disease (CVD), which are both major public health problems that requires urgent containment actions. Current controversies regarding MetS are focused on ascertain the unifying explanation of molecular and pathophysiological mechanisms originating the syndrome, involving insulin resistance and low-grade chronic inflammation. This review aims to present the clinical relevance of MetS and its complications, as well as the hypotheses addressing its etiopathogenic relation with CVD. We conclude that health policies should emphasize basic research promotion, timely detection and early treatment of MetS, which will help to reduce the risk of CVD and their impact on public health and health-care related costs.

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INTRODUCTION: Cardiovascular disease is the main cause of mortality worldwide. In women, its incidence increases at the sixth decade of life, coinciding with postmenopause. Whether this effect is due to menopause-related hormonal changes is not known. OBJECTIVE: To evaluate the differences in cardiovascular risk in pre- and postmenopausal women by means of the Globorisk risk scale, the triglyceride/high-density lipoproteins cholesterol (Tg/HDL-C) ratio and metabolic syndrome (MS) criteria. METHOD: Cross-sectional study that included 408 women from 40 to 60 years of age; anthropometric measurements and biochemical determinations were performed. The participants were classified as premenopausal and postmenopausal. Cardiovascular risk was assessed using the MS criteria, the Globorisk risk calculator and the Tg/HDL-C ratio. RESULTS: Postmenopausal women showed a significant increase in waist circumference, total cholesterol and triglycerides in comparison with premenopausal women. Significant associations were found between hormonal state and Globorisk measured cardiovascular risk (OR = 2.50; 95 % CI = 1.67-3.74) and the Tg/HDL-C ratio (OR = 1.66; 95 % CI = 1.09-2.52). CONCLUSION: Cardiovascular risk factors have a higher prevalence in postmenopause. The Globorisk scale and Tg/HDL-C ratio identify cardiovascular risk in postmenopausal women.

INTRODUCCIÓN: La enfermedad cardiovascular es la principal causa de mortalidad en el mundo. En la mujer se incrementa en la sexta década de la vida, coincidiendo con la posmenopausia. Se desconoce si este efecto se debe a cambios hormonales relacionados con la menopausia. OBJETIVO: Evaluar diferencias del riesgo cardiovascular en mujeres pre y posmenopáusicas mediante la escala de riesgo Globorisk, el índice triglicéridos/c-HDL (Tg/c-HDL) y los criterios de síndrome metabólico (SM). MÉTODOS: Estudio transversal que incluyó a 408 mujeres de 40 a 60 años; se realizaron mediciones antropométricas y bioquímicas. Las participantes se clasificaron en premenopáusicas y posmenopáusicas. El riesgo cardiovascular se evaluó utilizando los criterios de SM, calculadora de riesgo Globorisk y el índice Tg/c-HDL. RESULTADOS: Las mujeres en etapa posmenopáusica presentaron incremento significativo en la circunferencia de cintura, de colesterol total y triglicéridos, en comparación con las mujeres premenopáusicas. Se encontraron asociaciones significativas del estado hormonal con el riesgo cardiovascular evaluado por Globorisk (RM = 2.50, IC 95 % = 1.67-3.74) y con el índice Tg/c-HDL (RM = 1.66, IC 95 % = 1.09-2.52). CONCLUSIÓN: Los factores de riesgo cardiovascular tienen mayor prevalencia en la posmenopausia. La escala Globorisk y el índice Tg/c-HDL identifican el riesgo cardiovascular en la mujer posmenopáusica.

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