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COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status.
Thomas, T, Stefanoni, D, Reisz, JA, Nemkov, T, Bertolone, L, Francis, RO, Hudson, KE, Zimring, JC, Hansen, KC, Hod, EA, et al
JCI insight. 2020;5(14)
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There is increasing urgency for the development of Covid-19 therapies. Treatments preventing infection and decreasing the amount of virus in the body have largely been unsuccessful and so the focus has turned to host biological pathways, which may be altered by Covid-19 infection. This observational study of forty-nine Covid-19 positive and negative individuals aimed to determine alterations in the hosts metabolism. The results showed that Covid-19 infection was associated with disrupted host inflammatory and immune pathways. Markers for kidney dysfunction were also increased alongside raised blood sugar levels and fatty acids in the blood. It was concluded that inflammatory markers may be an indicator for disease severity and a target for Covid-19 therapy. Dietary therapy could be used to target blood fatty acid changes brought about by Covid-19 infection. This study could be used by healthcare professionals to understand that inflammation is increased in Covid-19 patients and in lieu of approved therapies, dietary intervention may be of benefit.
Abstract
BACKGROUNDReprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks.METHODSTo investigate metabolic effects of SARS-CoV-2 infection, we evaluated serum metabolites of patients with COVID-19 (n = 33; diagnosed by nucleic acid testing), as compared with COVID-19-negative controls (n = 16).RESULTSTargeted and untargeted metabolomics analyses identified altered tryptophan metabolism into the kynurenine pathway, which regulates inflammation and immunity. Indeed, these changes in tryptophan metabolism correlated with interleukin-6 (IL-6) levels. Widespread dysregulation of nitrogen metabolism was also seen in infected patients, with altered levels of most amino acids, along with increased markers of oxidant stress (e.g., methionine sulfoxide, cystine), proteolysis, and renal dysfunction (e.g., creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis. Interestingly, metabolite levels in these pathways correlated with clinical laboratory markers of inflammation (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen).CONCLUSIONIn conclusion, this initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.FUNDINGBoettcher Foundation Webb-Waring Biomedical Research Award; National Institute of General and Medical Sciences, NIH; and National Heart, Lung, and Blood Institute, NIH.
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Is waist-to-height ratio the best predictive indicator of hypertension incidence? A cohort study.
Rezende, AC, Souza, LG, Jardim, TV, Perillo, NB, Araújo, YCL, de Souza, SG, Sousa, ALL, Moreira, HG, de Souza, WKSB, do Rosário Gondim Peixoto, M, et al
BMC public health. 2018;18(1):281
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A variety of methods of measuring body fat are used as tools to predict the risk of developing certain lifestyle-related diseases such as high blood pressure. It is not yet clear which of these methods is the most accurate. The aim of this study was to evaluate and compare the effectiveness of using different measures of body fat to predict high blood pressure. The study was performed in Brazil. Adult volunteers with normal blood pressure were assessed for body fat using waist-to-height ratio (WHtR), body mass index (BMI) and waist circumference (WC), and then followed-up 13 years later to find out whether they had developed high blood pressure. 44% of the participants developed high blood pressure during the study period. BMI, WC and WHtR were all associated with the risk of high blood pressure and had similar accuracy in predicting the disease. However, the associations were only significant for women. The cut-off points for predicting high blood pressure agreed with current recommendations, except for the WC in men. The results suggest that both overall obesity (BMI) and central obesity (WC and WHtR) indicators can be used in this population to evaluate the risk of developing high blood pressure.
Abstract
BACKGROUND The best anthropometric indicator to verify the association between obesity and hypertension (HTN) has not been established. We conducted this study to evaluate and compare the discriminatory power of waist-to-height ratio (WHtR) in relation to body mass index (BMI) and waist circumference (WC) in predicting HTN after 13 years of follow-up. METHODS This study was an observational prospective cohort study performed in the city of Firminópolis, in Brazilian's midwest. The cohort baseline (phase 1) was initiated in 2002 with the evaluation of a representative sample of the normotensive population (≥ 18 years of age). The incidence of HTN was evaluated as the outcome (phase 2). Sociodemographic, dietary and lifestyle variables were used to adjust proportional hazards models and evaluate risk of HTN according to anthropometric indices. The areas under the receiver operating characteristic (ROC) curves were used to compare the predictive capacity of these indices. The best HTN predictor cut-offs were obtained based on sensitivity and specificity. RESULTS A total of 471 patients with a mean age of 38.9 ± 12.3 years were included in phase 1. The mean follow-up was 13.2 years, and 207 subjects developed HTN. BMI, WC and WHtR were associated with risk of HTN incidence and had similar power in predicting the disease. However, the associations were only significant for women. The cut-off points with a better HTN predictive capacity were in agreement with current recommendations, except for the WC in men. CONCLUSIONS The results suggest that both overall obesity (BMI) and central obesity (WC and WHtR) anthropometric indicators can be used in this population to evaluate the risk of developing hypertension.