The cardiovascular polypill as baseline treatment improves lipid profile and blood pressure regardless of body mass index in patients with cardiovascular disease. The Bacus study.

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.

In Vitro Exposure of Primary Human T Cells and Monocytes to Polyclonal Stimuli Reveals a Basal Susceptibility to Display an Impaired Cellular Immune Response and Develop Severe COVID-19.

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.

[Consensus on the use of iSGLT2 in the treatment of patients with type 2 diabetes mellitus]. / Documento de consenso sobre el uso de los iSGLT2 en el tratamiento de pacientes con diabetes mellitus tipo 2.

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.

Documento de consenso sobre el uso de los iSGLT2 en el tratamiento de pacientes con diabetes mellitus tipo 2 / Consensus on the use of iSGLT2 in the treatment of patients with type 2 diabetes mellitus

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.

Impact of Metabolic Syndrome in the Clinical Outcome of Disease by SARS-COV-2.

BACKGROUND: It has been observed that subjects with comorbidities related to metabolic syndrome (MetS) as hypertension, obesity, cardiovascular disease (CVD), and diabetes mellitus (DM2) show severe cases and a higher mortality by COVID-19. To date, there is little information available on the impact of the interaction between these comorbidities in the risk of death by COVID-19. AIM OF THE STUDY: To evaluate the impact of the combinations of MetS components in overall survival (OS) and risk of death among COVID-19 patients. METHODS: Using public data of the Ministry of Health, suspected, and confirmed COVID-19 cases from February 25-June 6, 2020 was analyzed. Mortality odds ratio (OR) was calculated with a univariate analysis (95% CI) and attributable risk. Interactions between components and survival curves were analyzed and a multivariate logistics regression analysis was conducted. RESULTS: The analysis included 528,651 cases out of which 202,951 were confirmed for COVID-19. Probabilities of OS among confirmed patients were 0.93, 0.89, 0.87, 0.86, and 0.83 while the OR of multivariate analysis was 1.83 (1.77-1.89), 2.58 (2.48-2.69), 2.83 (2.66-3.01), and 3.36 (2.83-3.99) for zero, one, two, three, and four MetS components, respectively. The combination with the highest risk was DM2 + hypertension at 2.22 (2.15-2.28), and the attributable risk for any component was 9.35% (9.21-9.49). Only the combination obesity + CVD showed no significant interaction. CONCLUSION: The presence of one MetS component doubles the risk of death by COVID-19, which was higher among patients with DM2 + hypertension. Only obesity and CVD do not interact significantly.

The Neutrophil-to-Monocyte Ratio and Lymphocyte-to-Neutrophil Ratio at Admission Predict In-Hospital Mortality in Mexican Patients with Severe SARS-CoV-2 Infection (Covid-19).

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.

Brain insulin circuit. From the basics to impact on the clinic.

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.

Six Month Polypill Therapy Improves Lipid Profile in Patients with Previous Acute Myocardial Infarction: The Heart-Mex Study.

BACKGROUND: Acute myocardial infarction (AMI) is a leading cause of death in Mexico. Atherogenic lipid profile is a key component in AMI. Thus, it is imperative to find drug therapies able to reduce atherogenic lipids in AMI patients and prevent subsequent myocardial infarctions. AIM OF THE STUDY: To investigate the effect of polypill (Sincronium®) alone or combined with beta blockers (BB) and/or thiazide diuretics (TD) on total cholesterol, triglycerides, low-density lipoproteins (LDL), high-density lipoproteins (HDL), and cardiovascular risk markers in a Mexican population with AMI. METHODS: Secondary AMI-prevention patients (n = 256) were included in the study and categorized into three groups depending on the drug scheme, as follows: polypill (n = 150), polypill+BB (n = 91), and polypill + BB + TD (n = 15). Lipid profile and cardiovascular risk markers were evaluated in each patient before and 6 months after drug therapy. RESULTS: The Wilcoxon-matched pairs signed rank test showed significant ∼25-30% reductions in total cholesterol, triglycerides, and LDL in the polypill group as compared to polypill + BB and polypill + BB + TD groups. On the contrary, HDL was significantly increased in polypill and polypill + BB groups. Polypill therapy showed more marked reductions in blood pressure, atherogenic index, Framingham risk score, and vascular age with respect to polypill + BB and polypill + BB + TD groups. CONCLUSION: This study demonstrates for the first time that polypill therapy without being combined with BB and TD is effective to improve the atherogenic lipid profile and cardiovascular risk markers in AMI patients. Further studies are needed to examine the efficacy of polypill in reducing the occurrence of a second AMI in the Mexican population.

[Asociación del estado hormonal con el riesgo cardiovascular evaluado por Globorisk en mujeres mexicanas].

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.

Metabolic Syndrome and Cardiovascular Disease: A Health Challenge.

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.

Correction: Family history and obesity in youth, their effect on acylcarnitine/aminoacids metabolomics and non-alcoholic fatty liver disease (NAFLD). Structural equation modeling approach.

[This corrects the article DOI: 10.1371/journal.pone.0193138.].

Family history and obesity in youth, their effect on acylcarnitine/aminoacids metabolomics and non-alcoholic fatty liver disease (NAFLD). Structural equation modeling approach.

BACKGROUND: Structural equation modeling (SEM) can help understanding complex functional relationships among obesity, non-alcoholic fatty liver disease (NAFLD), family history of obesity, targeted metabolomics and pro-inflammatory markers. We tested two hypotheses: 1) If obesity precedes an excess of free fatty acids that increase oxidative stress and mitochondrial dysfunction, there would be an increase of serum acylcarnitines, amino acids and cytokines in obese subjects. Acylcarnitines would be related to non-alcoholic fatty disease that will induce insulin resistance. 2) If a positive family history of obesity and type 2 diabetes are the major determinants of the metabolomic profile, there would be higher concentration of amino acids and acylcarnitines in patients with this background that will induce obesity and NAFLD which in turn will induce insulin resistance. METHODS/RESULTS: 137 normoglycemic subjects, mean age (SD) of 30.61 (8.6) years divided in three groups: BMI<25 with absence of NAFLD (G1), n = 82; BMI>30 with absence of NAFLD (G2), n = 24; and BMI>30 with NAFLD (G3), n = 31. Family history of obesity (any) was present in 53%. Both models were adjusted in SEM. Family history of obesity predicted obesity but could not predict acylcarnitines and amino acid concentrations (effect size <0.2), but did predict obesity phenotype. CONCLUSION: Family history of obesity is the major predictor of obesity, and the metabolic abnormalities on amino acids, acylcarnitines, inflammation, insulin resistance, and NAFLD.

Relationship of hyperuricemia with low density lipoprotein , liver function tests and markers of systemic inflammation in patients with morbid obesity. / Relación de la hiperuricemia con las lipoproteínas de baja densidad, las pruebas de funcionamiento hepático y los marcadores de inflamación sistémica en pacientes con obesidad mórbida.

Objective: To examine the relationship of uric acid levels with parameters of systemic inflammation, metabolic dysfunction as well as anthropometric parameters and liver function tests in subjects with morbid obesity. Methods: C-reactive protein (CRP), tumour necrosis factor-alpha, and interleukin 10 (IL-10) were analyzed in 49 women and men with morbid obesity, relating these markers with uric acid, hepatic function tests, anthropometric and metabolic parameters. Metabolic parameters as serum glucose level, glycosylated hemoglobin, total cholesterol, triglycerides, high density lipoprotein and low density lipoprotein (c-LDL) as well as hepatic function parameters were measured in all subjects. Results: -Comparing subjects with morbid obesity without hyperuricemia versus subjects with morbid obesity and hyperuricemia, an increase of total bilirubin values and gamma glutamil trans peptidase (GGT) was observed, suggesting hyperuricemia as associated with alteration of hepatic metabolism. Serum uric acid levels were statistically correlated with c-LDL, total bilirubin, albumin, GGT and CRP suggesting hyperuricemia could be associated with a dyslipidemic state, hepatic damage and increase in acute pro-inflammatory phase markers. In addition, a multiple linear regression analysis revealed that GGT and IL-10 were better predictors of the behavior of uric acid in the study population. Conclusion: These results suggest an -interdependent relationship among serum uric acid, CRP and IL-10 levels, which could be related to early hepatic -damage.

Nonalcoholic fatty liver disease can be predicted by retinal vascular changes in patients with obesity without hypertension or diabetes.

OBJECTIVE: To evaluate the utility of predicting nonalcoholic fatty liver disease (NAFLD) and obesity by retinal vascular changes (RVC) found in fundoscopy and to determine whether this is related to a low-grade inflammatory process. METHODS: We carried out a cross-sectional analysis that included 152 (ages 18-45 years) patients divided into four groups: NAFLD and BMI less than 25, absence of NAFLD and BMI less than 25, NAFLD and BMI more than 30, and absence of NAFLD and BMI more than 30. Retinal fundoscopy, hepatic ultrasound, metabolic profile, and cytokine measurement were performed. We calculated odds ratio [95% confidence interval (CI)], performed diagnostic utility tests, and carried out a 2 factorial analysis. RESULTS: Obesity was associated with RVC (odds ratio: 21.25; 95% CI: 8.79-51.4) and NAFLD [25 (9.07-72.6)]. NAFLD was associated with RVC [11.24 (4.98-26.48)], and the prediction of NAFLD showed a sensitivity of 75% (95% CI: 68-82) and a specificity of 81% (75-86); when RVC-obesity were combined, sensitivity increased to 90% (88-91.7), with a specificity of 85% (84-85.8). C-reactive protein was associated with the three factors, suggesting an independent contribution. Thin patients with RVC and NAFLD had higher concentrations of interleukin-2, interleukin-6, tumor necrosis factor-α, and interferon-γ. CONCLUSION: NAFLD in patients with obesity without diabetes or hypertension can be predicted by RVC, a noninvasive technique carried out by eye fundoscopy. NAFLD alone can drive inflammatory conditions in the absence of obesity that manifests as RVC.

Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients.

Morbid obesity has been shown to increase the risk to develop hepatic steatosis, also referred to as non-alcoholic fatty liver disease (NAFLD). Emerging evidence suggests that the severity of NAFLD may associate with increased serum levels of inflammatory markers as well as decreased concentration of mediators with anti-inflammatory actions, such as tumor necrosis factor alpha (TNF-α) and interleukin (IL) 10, respectively. We thus examined the serum levels of TNF-α and IL-10 in 102 morbidly obese women and men (body mass index > 40 kg/m(2)), exhibiting different grades of NAFLD. Blood glucose, glycated hemoglobin, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, high- and low-density lipoproteins, parameters of liver function, TNF-α, and IL-10 were measured in each subject. The stage of NAFLD was estimated by abdominal ultrasound imaging. In comparison with morbidly obese subjects without steatosis, morbidly obese patients with NAFLD showed increased age (39.23 ± 9.80 years), HOMA-IR (6.74 ± 1.62), total cholesterol (219.7 ± 9.58 mg/dl), aspartate aminotransferase (36.25 ± 3.24 UI/l), gamma-glutamyl transpeptidase (37.12 ± 3.41 UI/l), and TNF-α (37.41 ± 1.72 pg/ml) as well as decreased serum levels of IL-10 (61.05 ± 2.43 pg/ml). Interestingly, the systemic levels of TNF-α increased, while IL-10 decreased in accordance with the severity of NAFLD, which supports a role for systemic inflammatory mediators in promoting steatosis progression. Further clinical prospective studies need to be addressed to elucidate the role of TNF-α and IL-10 in the development of NAFLD while also establishing their clinical utility in the assessment of morbidly obese patients at higher risk to develop severe steatosis.

[Low-grade systemic inflammation and the development of metabolic diseases: from the molecular evidence to the clinical practice]. / Inflamación sistémica de grado bajo y su relación con el desarrollo de enfermedades metabólicas: de la evidencia molecular a la aplicación clínica.

BACKGROUND: Systemic inflammation is characterised by high circulating levels of inflammatory cytokines and increased macrophage infiltration in peripheral tissues. Most importantly, this inflammatory state does not involve damage or loss of function of the infiltrated tissue, which is a distinctive feature of the low-grade systemic inflammation. The term "meta-inflammation" has also been used to refer to the low-grade systemic inflammation due to its strong relationship with the development of cardio-metabolic diseases in obesity. OBJECTIVE: A review is presented on the recent clinical and experimental evidence concerning the role of adipose tissue inflammation as a key mediator of low-grade systemic inflammation. Furthermore, the main molecular mechanisms involved in the inflammatory polarization of macrophages with the ability to infiltrate both the adipose tissue and the vascular endothelium via activation of toll-like receptors by metabolic damage-associated molecular patterns, such as advanced glycation-end products and oxidized lipoproteins, is discussed. Finally, a review is made of the pathogenic mechanisms through which the low-grade systemic inflammation contributes to develop insulin resistance, dyslipidaemia, atherogenesis, type 2 diabetes, and hypertension in obese individuals. CONCLUSIONS: A better understanding of the molecular mechanisms of low-grade systemic inflammation in promoting cardio-metabolic diseases is necessary, in order to further design novel anti-inflammatory therapies that take into consideration clinical data, as well as the circulating levels of cytokines, immune cells, and metabolic damage-associated molecular patterns in each patient.

Reduced systemic levels of IL-10 are associated with the severity of obstructive sleep apnea and insulin resistance in morbidly obese humans.

Obstructive sleep apnea (OSA) has been related to elevation of inflammatory cytokines and development of insulin resistance in morbidly obese (MO) subjects. However, it is still unclear whether the systemic concentration of anti-inflammatory mediators is also affected in MO subjects directly related to the severity of OSA and level of insulin resistance. Normal weight and MO subjects were subjected to overnight polysomnography in order to establish the severity of OSA, according to the apnea-hypopnea index (AHI). Blood samples were obtained for estimation of total cholesterol and triglycerides, insulin, glucose, insulin resistance, tumor necrosis factor alpha (TNF-α), interleukin 12 (IL12), and interleukin 10 (IL-10). Serum levels of IL-10 were significantly lower in MO subjects with OSA than in MO and control individuals without OSA. Besides being inversely associated with serum TNF-α and IL-12, decreased IL-10 levels were significantly related to increased AHI, hyperinsulinemia, and insulin resistance. Serum IL-10 is significantly reduced in morbidly obese subjects with severe OSA while also showing a clear relationship with a state of hyperinsulinemia and insulin resistance probably regardless of obesity in the present sample. It may be of potential clinical interest to identify the stimulatory mechanisms of IL-10 in obese individuals with OSA.

Hyperleptinemia is associated with parameters of low-grade systemic inflammation and metabolic dysfunction in obese human beings.

Leptin is an adipose tissue-derived hormone that has been involved in hypothalamic and systemic inflammation, altered food-intake patterns, and metabolic dysfunction in obese mice. However, it remains unclear whether leptin has a relationship with parameters of systemic inflammation and metabolic dysfunction in humans. We thus evaluated in a cross-sectional study the circulating levels of leptin in 40 non-obese and 41 obese Mexican individuals, examining their relationship with tumor necrosis factor alpha (TNF-α), interleukin (IL) 12, IL-10, central obesity, serum glucose and insulin levels, and serum triglyceride and cholesterol concentrations. Circulating levels of leptin, TNF-α, IL-12, IL-10, and insulin were measured by ELISA, while concentrations of glucose, triglyceride, and cholesterol were determined by enzymatic assays. As expected, serum levels of leptin exhibited a significant elevation in obese individuals as compared to non-obese subjects, showing a clear association with increased body mass index (r = 0.4173), central obesity (r = 0.4678), and body fat percentage (r = 0.3583). Furthermore, leptin also showed a strong relationship with serum TNF-α (r = 0.6989), IL-12 (r = 0.3093), and IL-10 (r = -0.5691). Interestingly, leptin was also significantly related with high concentrations of fasting glucose (r = 0.5227) and insulin (r = 0.2229), as well as elevated levels of insulin resistance (r = 0.3611) and circulating triglyceride (r = 0.4135). These results suggest that hyperleptinemia is strongly associated with the occurrence of low-grade systemic inflammation and metabolic alteration in obese subjects. Further clinical research is still needed to determine whether hyperleptinemia may be a potential marker for recognizing the advent of obesity-related metabolic disorders in human beings.

Posición de consenso sobre las bebidas con edulcorantes no calóricos y su relación con la salud / Consensus about beverages with non-caloric sweeteners and its relation to health

Las principales bebidas consumidas por los mexicanos son los refrescos, aguas frescas, jugos, leche entera, café y té con azúcar agregada, atole, bebidas alcohólicas y bebidas energizantes. Las bebidas con edulcorantes no calóricos pueden ser útiles en el control de enfermedades crónicas, su ingesta diaria aceptable (IDA) es para acesulfame K 40mg/kg, aspartame 15mg/kg, ciclamato 11mg/kg, sacarina 5mg/kg, sucralosa 15mg/kg, Estevia/rebaudiósido A 4mg/kg. Aspartame: Es 200 veces más dulce que el azúcar. No debe administrarse en pacientes con fenilcetonuria. Acesulfame K: Es 100-200 veces más dulce que el azúcar. Se absorbe en el intestino delgado y su excreción es renal. Sin evidencia de efectos nocivos a la salud. Sacarina: Se absorbe a nivel intestinal y se excreta vía renal sin metabolizarse. Sin efectos tóxicos. Sucralosa: Es 600 veces más dulce que el azúcar. El proceso de cloración le da resistencia al calor, por lo que los alimentos que lo contienen se pueden calentar sin perder su característica edulcorante y sin efectos tóxicos. Estevia: Edulcorante natural sin efectos adversos. El papel de los edulcorantes no calóricos en el desarrollo de hiperinsulinemia, su posible impacto en la reserva pancreática o niveles de GLP-1 continúa en estudio. El uso de bebidas con edulcorantes no calóricos es una alternativa que permite a los pacientes el acceso a bebidas de mayor agrado. No hay contraindicación para su uso en adultos mayores, en el embarazo, en niños ni adolescentes siempre y cuando se cuiden sus necesidades nutricionales básicas y no sustituya otras intervenciones fundamentales.

The main beverages that are drunk by Mexican people are sodas, fresh water with sugar, juice, milk, coffee and tea with sugar, atole, alcoholic and energetic beverages. The beverages with non-caloric sweeteners might be useful to control chronic diseases. The acceptable daily intake of acesulfame K is 40mg/kg, aspartame 15mg/kg, cyclamate 11mg/kg, saccharin 5mg/kg, sucralose 15mg/kg, stevia/ rebaudioside A 4mg/kg. Aspartame: It is 200 times sweeter than sugar. This sweetener must not be given to patients with phenylketonuria. Acesulfame K: It is 100-200 times sweeter than sugar. Its absorption is in small intestine and has renal excretion. There is no evidence of adverse health effects. Saccharine: It is absorbed in the intestine and has renal excretion but without being metabolized. No toxic effects. Sucralose: It is 600 times sweeter than sugar. The chlorination process gives the property of being heat resistant, without losing their sweet taste. No toxic effects for health. Stevia: Natural sweetener. No adverse effects. The role of non-caloric sweeteners in the development of hyperinsulinemia, its impact on the pancreatic reserve or the GLP-1 levels is still on study. In general, for patients with chronic diseases the beverages with non-caloric sweeteners may be an alternative that let them have beverages with better taste. There's no contraindication in the use of non-caloric sweeteners in seniors, pregnancy, children or teenagers as long as their basic nutritional needs are respected, also that this action doesn't replace other important interventions.

Elevated triglycerides/HDL-cholesterol ratio associated with insulin resistance.

BACKGROUND: Cardiovascular disease is the main cause of death worldwide and insulin resistance (IR) plays an important role for its development. In addition, IR has been associated with hypertension and metabolic syndrome according to the triglyceride/HDL-cholesterol (TGL/HDL) ratio. We undertook this study to determine whether the TGL/HDL ratio is associated with IR in apparently healthy subjects. METHODS: A cross-sectional study including healthy men and nonpregnant women was performed. Individuals with IR were compared against subjects without IR. Variables studied were age, gender, body mass index, and waist circumference. Exclusion criteria were chronic diseases such as renal disease, hepatic disease, malignancy, and diabetes. RESULTS: A total of 177 subjects were enrolled, 117 females (66.1%) and 60 males (33.9%). Of these, 145 (93 females and 52 males) with IR were compared against 32 subjects (24 females and 8 males) without IR. Elevated ratio TGL/HDL ratio was detected in 89 (61.4%) and 12 (38.6%) subjects with and without IR, respectively. The elevated TGL/HDL ratio was significantly associated with IR (OR 2.64, 95% CI = 1.12-6.29). CONCLUSIONS: In apparently healthy subjects, elevated TGL/HDL ratio was significantly associated with the presence of IR.