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The effects of non-nutritive sweeteners (NNS) on the gut microbiota are an area of increasing research interest due to their potential influence on weight gain, insulin resistance, and inflammation. Studies have shown that mice and rats fed saccharin develop weight gain and metabolic alterations, possibly related to changes in gut microbiota. Here, we hypothesized that chronic exposure to a commercial NNS would change the gut microbiota composition in Wistar rats when compared to sucrose exposure. To test this hypothesis, Wistar rats were fed either NNS- or sucrose-supplemented yogurt for 17 weeks alongside standard chow (ad libitum). The gut microbiome was assessed by 16S rDNA deep sequencing. Assembly and quantification were conducted using the Brazilian Microbiome Project pipeline for Ion Torrent data with modifications. Statistical analyses were performed in the R software environment. We found that chronic feeding of a commercial NNS-sweetened yogurt to Wistar rats, within the recommended dose range, did not significantly modify gut microbiota composition in comparison to sucrose-sweetened yogurt. Our findings do not support the hypothesis that moderate exposure to NNS is associated with changes in gut microbiota pattern compared to sucrose, at least in this experimental model.
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In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats.
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Ingestión de Energía , Resistencia a la Insulina , Sacarina/efectos adversos , Gusto , Aumento de Peso , Animales , Glucemia/metabolismo , Agua Potable , Ayuno , Transportador de Glucosa de Tipo 2/genética , Transportador de Glucosa de Tipo 2/metabolismo , Insulina/sangre , Leptina/sangre , Masculino , Péptido YY/sangre , Ratas , Sacarina/administración & dosificación , YogurRESUMEN
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease affecting 30% of the world's population and is often associated with metabolic disorders such as metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease. This review is an update of the Brazilian Diabetes Society (Sociedade Brasileira de Diabetes [SBD]) evidence-based guideline for the management of MASLD in clinical practice. METHODS: The methodology was published previously and was defined by the internal institutional steering committee. The SBD Metabolic Syndrome and Prediabetes Department drafted the manuscript, selecting key clinical questions for a narrative review using MEDLINE via PubMed with the MeSH terms [diabetes] and [fatty liver]. The best available evidence was reviewed, including randomized clinical trials (RCTs), meta-analyses, and high-quality observational studies related to MASLD. RESULTS AND CONCLUSIONS: The SBD Metabolic Syndrome and Prediabetes Department formulated 9 recommendations for the management of MASLD in people with prediabetes or T2D. Screening for the risk of advanced fibrosis associated with MASLD is recommended in all adults with prediabetes or T2D. Lifestyle modification (LSM) focusing on a reduction in body weight of at least 5% is recommended as the first choice for these patients. In situations where LSMs are insufficient to achieve weight loss, the use of anti-obesity medications is recommended for those with a body mass index (BMI) ≥ 27 kg/m2. Pioglitazone and glucagon-like peptide-1 receptor agonists (GLP-1RA) monotherapy are the first-line pharmacological treatments for steatohepatitis in people with T2D, and sodium-glucose cotransporter-2 (SGLT2) inhibitors may be considered in this context. The combination of these agents may be considered in the treatment of steatohepatitis and/or fibrosis, and bariatric surgery should be considered in patients with a BMI ≥ 35 kg/m2, in which the combination of LSM and pharmacotherapy has not been shown to be effective in improving MASLD.
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BACKGROUND: Chronic kidney disease (CKD) affects around 10% of the global population and has been estimated to affect around 50% of individuals with type 2 diabetes and 50% of those with heart failure. The guideline-recommended approach is to manage with disease-modifying therapies, but real-world data suggest that prescribing rates do not reflect this in practice. OBJECTIVE: To develop a cross-specialty consensus on optimal management of the patient with CKD using a modified Delphi method. DESIGN: An international steering group of experts specialising in internal medicine, endocrinology/diabetology, nephrology and primary care medicine developed 42 statements on aspects of CKD management including identification and screening, risk factors, holistic management, guidelines, cross-specialty alignment and education. Consensus was determined by agreement using an online survey. PARTICIPANTS: The survey was distributed to cardiologists, nephrologists, endocrinologists and primary care physicians across 11 countries. MAIN OUTCOMES AND MEASURES: The threshold for consensus agreement was established a priori by the steering group at 75%. Stopping criteria were defined as a target of 25 responses from each country (N=275), and a 4-week survey period. RESULTS: 274 responses were received in December 2022, 25 responses from Argentina, Australia, Brazil, Guatemala, Mexico, Singapore, South Korea, Taiwan, Thailand, Turkey and 24 responses from Egypt. 53 responses were received from cardiologists, 52 from nephrologists, 55 from endocrinologists and 114 from primary care physicians. 37 statements attained very high agreement (≥90%) and 5 attained high agreement (≥75% and <90%). Strong alignment between roles was seen across the statements, and different levels of experience (2-5 years or 5+ years), some variation was observed between countries. CONCLUSIONS: There is a high degree of consensus regarding aspects of CKD management among healthcare professionals from 11 countries. Based on these strong levels of agreement, the steering group derived 12 key recommendations focused on diagnosis and management of CKD.
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Diabetes Mellitus Tipo 2 , Nefrología , Insuficiencia Renal Crónica , Humanos , Consenso , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , Nefrólogos , Nefrología/métodosRESUMEN
It has been suggested that the use of nonnutritive sweeteners (NNSs) can lead to weight gain, but evidence regarding their real effect in body weight and satiety is still inconclusive. Using a rat model, the present study compares the effect of saccharin and aspartame to sucrose in body weight gain and in caloric intake. Twenty-nine male Wistar rats received plain yogurt sweetened with 20% sucrose, 0.3% sodium saccharin or 0.4% aspartame, in addition to chow and water ad libitum, while physical activity was restrained. Measurements of cumulative body weight gain, total caloric intake, caloric intake of chow and caloric intake of sweetened yogurt were performed weekly for 12 weeks. Results showed that addition of either saccharin or aspartame to yogurt resulted in increased weight gain compared to addition of sucrose, however total caloric intake was similar among groups. In conclusion, greater weight gain was promoted by the use of saccharin or aspartame, compared with sucrose, and this weight gain was unrelated to caloric intake. We speculate that a decrease in energy expenditure or increase in fluid retention might be involved.
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Aspartame/administración & dosificación , Sacarina/administración & dosificación , Sacarosa/administración & dosificación , Aumento de Peso/efectos de los fármacos , Animales , Ingestión de Energía , Metabolismo Energético , Masculino , Ratas , Ratas Wistar , Saciedad/efectos de los fármacos , Edulcorantes/administración & dosificación , YogurRESUMEN
Recent data from meta-analyses of randomized clinical trials (RCTs) suggest that dietary intake of coconut oil, rich in saturated fatty acids, does not result in cardiometabolic benefits, nor in improvements in anthropometric, lipid, glycemic, and subclinical inflammation parameters. Nevertheless, its consumption has surged in recent years all over the world, a phenomenon which can possibly be explained by an increasing belief among health professionals that this oil is as healthy as, or perhaps even healthier than, other oils, in addition to social network misinformation spread. The objective of this review is to present nutritional and epidemiological aspects related to coconut oil, its relationship with metabolic and cardiovascular health, as well as possible hypotheses to explain its high rate of consumption, in spite of the most recent data regarding its actual effects.
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Enfermedades Cardiovasculares , Salud Pública , Humanos , Aceite de Coco , Ácidos Grasos , Factores de Riesgo , Enfermedades Cardiovasculares/etiología , Aceites de Plantas/uso terapéutico , Grasas de la DietaRESUMEN
INTRODUCTION: For individuals diagnosed with diabetes mellitus, the practice of properly oriented physical exercises brings significant benefits to the individual's health and is considered an indispensable tool for metabolic management. The individualization of exercise routines is an essential aspect for therapeutic success, despite the need to consider some general recommendations. This review is an authorized literal translation of the Brazilian Society of Diabetes (SBD) Guidelines 2021-2022, which is based on scientific evidence and provides guidance on physical activities and exercises aimed at individuals with type 1 and 2 diabetes. METHODS: SBD designated 9 specialists from its "Department of Diabetes, Exercise & Sports" to author chapters on physical activities and exercises directed to individuals with type 1 and 2 diabetes. The aim of these chapters was to highlight recommendations in accordance with Evidence Levels, based on what is described in the literature. These chapters were analyzed by the SBD Central Committee, which is also responsible for the SBD 2021-2022 guidelines. Main clinical inquiries were selected to perform a narrated review by using MEDLINE via PubMed. Top available evidence, such as high-quality clinical trials, large observational studies and meta-analyses related to physical activity and exercise advisory, were analyzed. The adopted MeSh terms were [diabetes], [type 1 diabetes], [type 2 diabetes], [physical activity] [physical exercise]. RESULTS: 17 recommendations were defined by the members. For this review, it was considered different Evidence Levels, as well as different Classes of Recommendations. As to Evidence Levels, the following levels were contemplated: Level A) More than one randomized clinical trial or a randomized clinical trial meta-analysis with low heterogeneity. Level B) Meta analysis with observational studies, one randomized clinical trial, sizeable observational studies and sub-groups analysis. Level C) Small non-randomized studies, cross-sectional studies, case control studies, guidelines or experts' opinions. In respect to Recommendation Classes, the following criteria were adopted: I. "Recommended": Meaning there was a consent of more than 90% of the panel; IIa. "Must be considered": meaning there is a general preference of the panel which 70-90% agrees; IIb. "Can be considered". 50-70% agrees; III Not recommended: There is a consensus that the intervention should not be performed. CONCLUSION: Physical exercise aids on the glycemic control of type 2 diabetes individuals while also decreasing cardiovascular risk in individuals with type 1 and 2 diabetes. Individuals diagnosed with diabetes should perform combined aerobic and resistance exercises in order to manage the disease. In addition, exercises focusing on flexibility and balance should be specially addressed on elderly individuals. Diabetes individuals using insulin as therapeutic treatment should properly monitor glycemia levels before, during and after exercise sessions to minimize health incidents, such as hypoglycemia.
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BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.
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Existing risk prediction scores based on clinical and laboratory variables have been considered inaccurate in patients with Type 2 Diabetes Mellitus (T2DM). Circulating concentrations of natriuretic peptides have been used to aid in the diagnosis and to predict outcomes in heart failure. However, there is a growing body of evidence for the use of natriuretic peptides measurements, mainly N-terminal pro-B-type natriuretic peptide (NT-proBNP), as a tool in risk stratification for individuals with T2DM. Studies have demonstrated the ability of NT-proBNP to improve outcomes prediction when incorporated into multivariate models. More recently, evidence has emerged of the discriminatory power of NT-proBNP, demonstrating, as a single variable, a similar and even superior ability to multivariate risk models for the prediction of death and cardiovascular events in individuals with T2DM. Natriuretic peptides are synthesized and released from the myocardium as a counter-regulatory response to increased cardiac wall stress, sympathetic tone, and vasoconstriction, acting on various systems and affecting different biological processes. In this article, we present a review of the accumulated knowledge about these biomarkers, underscoring the strength of the evidence of their predictive ability for fatal and non-fatal outcomes. It is likely that, by influencing the functioning of many organs, these biomarkers integrate information from different systems. Although not yet recommended by guidelines, measurement of natriuretic peptides, and particularly NT-proBNP, should be strongly considered in the risk stratification of individuals with T2DM.
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BACKGROUND: Interleukin-6 (IL-6) is an inflammation-related cytokine associated with an elevated risk of cardiovascular events. In a previous study, we demonstrated that increased IL-6 was predictive of sub-clinical atherosclerotic coronary disease in intermediate-risk patients undergoing coronary angiography. In the present study, we investigated whether increased serum IL-6 is predictive of cardiovascular events in high-risk patients. METHODS: In this observational study, consecutive patients referred for elective coronary angiography due to stable chest pain/myocardial ischemia had IL-6 measured immediately before the procedure. Long-term follow-up was performed by phone call or e-mail, and their clinical registries were revised. The primary outcome was a composite of new myocardial infarction, new ischemic stroke, hospitalization due to heart failure, new coronary revascularization, cardiovascular death, and death due to all causes. RESULTS: From 141 patients submitted to coronary angiography and IL-6 analysis, 100 had complete follow-up data for a mean of 5.7 years. The median age was 61.1 years, 44% were men, and 61% had type-2 diabetes. The median overall time-to-event for the primary outcome was 297 weeks (95% confidence interval [CI] 266.95-327.16). A receiver operator characteristic curve defined the best cut-off value of baseline serum IL-6 (0.44 pg/mL) with sensitivity (84.37%) and specificity (38.24%) to define two groups. High (> 0.44 pg/mL) IL-6 levels were predictive of cardiovascular events. (p for interaction = 0.015) (hazard ratio = 2.81; 95% CI 1.38-5.72, p = 0.01). Subgroup analysis did not find interactions between patients with or without diabetes, obesity, or hypertension. CONCLUSION: In conclusion, an interleukin-6 level higher than 0.44 pg/mL, obtained just before elective coronary angiography, was associated with a poorer prognosis after a mean of 5,7-year. A pre-procedure IL-6 below 0.44 pg/mL, on the other hand, has a very good negative predictive value, suggesting a good prognosis, and may be useful to better indicate coronary angiography in high-risk patients. .
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BACKGROUND: Insulin therapy regimens for people with type 1 diabetes (PWT1D) should mimic the physiological insulin secretion that occurs in individuals without diabetes. Intensive insulin therapy, whether by multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII), constitutes the fundamental therapy from the initial stages of type 1 diabetes (T1D), at all ages. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021-2022. This evidence-based guideline supplies guidance on insulin therapy in T1D. METHODS: The methods were published elsewhere in earlier SBD guidelines and was approved by the Internal Institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated fourteen experts to constitute the Central Committee, designed to regulate the method review of the manuscripts, and judge the degrees of recommendations and levels of evidence. SBD Type 1 Diabetes Department drafted the manuscript selecting key clinical questions to do a narrative review using MEDLINE via PubMed, with the best evidence available, including high-quality clinical trials, metanalysis, and large observational studies related to insulin therapy in T1D, by using the Mesh terms [type 1 diabetes] and [insulin]. RESULTS: Based on extensive literature review the Central Committee defined ten recommendations. Three levels of evidence were considered: A. Data from more than one randomised clinical trial (RCT) or one metanalysis of RCTs with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single RCT, or a pre-specified subgroup analysis. C: Data from small or non-randomised studies, exploratory analysis, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panellists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa if 75-89% of agreement; IIb if 50-74% of agreement, and III, when most of the panellist recommends against a defined treatment. CONCLUSIONS: In PWT1D, it is recommended to start insulin treatment immediately after clinical diagnosis, to prevent metabolic decompensation and diabetic ketoacidosis. Insulin therapy regimens should mimic insulin secretion with the aim to achieve glycemic control goals established for the age group. Intensive treatment with basal-bolus insulin therapy through MDI or CSII is recommended, and insulin analogues offers some advantages in PWT1D, when compared to human insulin. Periodic reassessment of insulin doses should be performed to avoid clinical inertia in treatment.
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BACKGROUND: Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021-2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. METHODS: The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. RESULTS: The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75-89% of agreement; IIb 50-74% of agreement, and III, when most of the panelist recommends against a defined treatment. CONCLUSIONS: To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin-angiotensin-aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients' survival.
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This paper reviews involvement of the serotonergic system in the control of food intake and satiety. It is of great interest to understand the relevance of this system for physiological control of energy balance and obesity. Over 35 years of research suggest that serotonin (5-HT) plays an important role in satiety. Thus, the serotonergic system has been a viable target for weight control. The 5-HT has control over hunger and satiety through different receptors with distinct functions. The 5-HT2C receptor may be more important in the relationship between food intake and energy balance. This review will discuss the mechanisms of the serotonergic system involved in the control of food intake and satiety.
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Ingestión de Alimentos/fisiología , Hambre/fisiología , Hipotálamo/metabolismo , Saciedad/fisiología , Agonistas de Receptores de Serotonina/fisiología , Animales , Humanos , Neurotransmisores/fisiología , Obesidad/tratamiento farmacológico , Saciedad/efectos de los fármacos , Serotonina/fisiología , Agonistas del Receptor de Serotonina 5-HT1/fisiología , Agonistas del Receptor de Serotonina 5-HT2/fisiologíaRESUMEN
Statins are among the most widely prescribed medicines in the world and have proved their value in reducing cardiovascular events and mortality. Many patients report adverse effects that lead to interruption of treatment. This review aims to individualize statin treatment, considering efficacy for reducing cardiovascular risk and safety, in the setting of specific diseases, to minimize the side effects and improve compliance. We gathered evidence that may help clinicians to choose specific statins in different clinical situations, such as the risk of new diabetes, chronic kidney disease, liver disease, human immunodeficiency virus infection, organ transplant, heart failure and elderly people. Efficacy of statins is well established in a large number of clinical conditions. Therefore, main objective is to revise statin in specific clinical settings, based on pharmacokinetics, safety, drug metabolism and interactions to provide the best choice in different clinical scenarios.
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Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Anciano , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéuticoRESUMEN
BACKGROUND: The aim of this study is to evaluate the impact of diabetes, hypertension, cardiovascular disease and the use of angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB) with severity (invasive mechanical ventilation or intensive care unit admission or O2 saturation < 90%) and mortality of COVID-19 cases. METHODS: Systematic review of the PubMed, Cochrane Library and SciELO databases was performed to identify relevant articles published from December 2019 to 6th May 2020. Forty articles were included involving 18.012 COVID-19 patients. RESULTS: The random-effect meta-analysis showed that diabetes mellitus and hypertension were moderately associated respectively with severity and mortality for COVID-19: Diabetes [OR 2.35 95% CI 1.80-3.06 and OR 2.50 95% CI 1.74-3.59] Hypertension: [OR 2.98 95% CI 2.37-3.75 and OR 2.88 (2.22-3.74)]. Cardiovascular disease was strongly associated with both severity and mortality, respectively [OR 4.02 (2.76-5.86) and OR 6.34 (3.71-10.84)]. On the contrary, the use of ACEI/ARB, was not associate with severity of COVID-19. CONCLUSION: In conclusion, diabetes, hypertension and especially cardiovascular disease, are important risk factors for severity and mortality in COVID-19 infected people and are targets that must be intensively addressed in the management of this infection.
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INTRODUCTION: New antihyperglycemic medications have been proven to have cardiovascular (CV) and renal benefits in type 2 diabetes mellitus (T2DM); however, an evidence-based decision tree in specific clinical scenarios is lacking. MATERIALS AND METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs), with trial sequential analysis (TSA). Randomized controlled trial inclusion criteria were patients with T2DM from 1 of these subgroups: elderly, obese, previous atherosclerotic CV disease (ASCVD), previous coronary heart disease (CHD), previous heart failure (HF), or previous chronic kidney disease (CKD). Randomized controlled trials describing those subgroups with at least 48 weeks of follow-up were included. Outcomes: 3-point major adverse cardiovascular events (MACE), CV death, hospitalization due to HF, and renal outcomes. We performed direct meta-analysis with the number of events in the intervention and control groups in each subset, and the relative risk of the events was calculated. RESULTS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) were the only antihyperglycemic agents related to a reduction in CV events in different populations. For obese and elderly populations, GLP-1 RA were associated with benefits in 3-point MACE; for patients with ASCVD, both SGLT2i and GLP-1 RA had benefits in 3-point MACE, while for patients with CHD, only SGLT2i were beneficial. CONCLUSIONS: SGLT2i and GLP-1 RA reduced CV events in selected populations: SGLT2i led to a reduction in events in patients with previous CHD, ASCVD, and HF. GLP-1 RA led to a reduction in CV events in patients with ASCVD, elderly patients, and patients with obesity. Trial sequential analysis shows that these findings are conclusive. This review opens a pathway towards evidence-based, personalized treatment of T2DM. REGISTRATION: PROSPERO CRD42019132807.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hipoglucemiantes/uso terapéutico , Incretinas/uso terapéutico , Atención Dirigida al Paciente , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Manejo de la Enfermedad , Receptor del Péptido 1 Similar al Glucagón/agonistas , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. METHODS: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5-7.5%. When HbA1c is 7.5-9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction (< 40%) and glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30-60 mL/min/1.73 m2 or eGFR 30-90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.
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This study aimed to compare the effect of high-intensity interval training (HIIT) with moderate-intensity continuous training (MCT) on endothelial function, oxidative stress and clinical fitness in patients with type 1 diabetes. Thirty-six type 1 diabetic patients (mean age 23.5 ± 6 years) were randomized into 3 groups: HIIT, MCT, and a non-exercising group (CON). Exercise was performed in a stationary cycle ergometers during 40 min, 3 times/week, for 8 weeks at 50-85% maximal heart rate (HRmax) in HIIT and 50% HRmax in MCT. Endothelial function was measured by flow-mediated dilation (FMD) [endothelium-dependent vasodilation (EDVD)], and smooth-muscle function by nitroglycerin-mediated dilation [endothelium-independent vasodilation (EIVD)]. Peak oxygen consumption (VO2peak) and oxidative stress markers were determined before and after training. Endothelial dysfunction was defined as an increase < 8% in vascular diameter after cuff release. The trial is registered at ClinicalTrials.gov, identifier: NCT03451201. Twenty-seven patients completed the 8-week protocol, 9 in each group (3 random dropouts per group). Mean baseline EDVD was similar in all groups. After training, mean absolute EDVD response improved from baseline in HIIT: + 5.5 ± 5.4%, (P = 0.0059), but remained unchanged in MCT: 0.2 ± 4.1% (P = 0.8593) and in CON: -2.6 ± 6.4% (P = 0.2635). EDVD increase was greater in HIIT vs. MCT (P = 0.0074) and CON (P = 0.0042) (ANOVA with Bonferroni). Baseline VO2peak was similar in all groups (P = 0.96). VO2peak increased 17.6% from baseline after HIIT (P = 0.0001), but only 3% after MCT (P = 0.055); no change was detected in CON (P = 0.63). EIVD was unchanged in all groups (P = 0.18). Glycemic control was similar in all groups. In patients with type 1 diabetes without microvascular complications, 8-week HIIT produced greater improvement in endothelial function and physical fitness than MCT at a similar glycemic control.
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ABSTRACT Recent data from meta-analyses of randomized clinical trials (RCTs) suggest that dietary intake of coconut oil, rich in saturated fatty acids, does not result in cardiometabolic benefits, nor in improvements in anthropometric, lipid, glycemic, and subclinical inflammation parameters. Nevertheless, its consumption has surged in recent years all over the world, a phenomenon which can possibly be explained by an increasing belief among health professionals that this oil is as healthy as, or perhaps even healthier than, other oils, in addition to social network misinformation spread. The objective of this review is to present nutritional and epidemiological aspects related to coconut oil, its relationship with metabolic and cardiovascular health, as well as possible hypotheses to explain its high rate of consumption, in spite of the most recent data regarding its actual effects.