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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Despite improvements in cardiovascular diseases &#40;CVD&#41; diagnosis and treatment&#44; continuous aging and the sedentary lifestyle of modern societies have led to an increased incidence of heart and blood vessels diseases&#46; The World Health Organization estimates that CVDs account for 31&#37; of all global deaths&#44; increasing to over 50&#37; mortality among individuals with diabetes mellitus&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">1</span></a> This chronic state of hyperglycemia is normally associated with defects in insulin secretion and insulin action&#44; also known as insulin resistance &#40;IR&#41;&#44; or both&#46; Moreover&#44; defects in uptake and oxidation of glucose&#44; glycogen synthesis&#44; and in the ability to suppress lipid oxidation are some of the metabolic alterations due to the IR state&#46; These metabolic events consequently trigger oxidative stress and inflammatory responses that ultimately lead to cell damage&#46; Thus&#44; in hyperglycemia and IR states&#44; metabolic&#44; structural and functional alterations have been shown to affect multiple tissues&#44; including the heart&#44; skeletal muscle&#44; liver&#44; and adipose tissue&#46; In the heart and vasculature&#44; the aforementioned IR-induced changes have been associated with the incidence of diabetic cardiomyopathy&#44; coronary artery disease&#44; myocardial ischemia&#44; and ultimately heart failure&#46; Despite this strong link between IR and increased CVD incidence&#44; the proportion of CVD that can be attributed to IR remains unclear&#46; Through a meta-analysis&#44; IR measured using the homeostasis model assessment &#40;HOMA&#41;&#44; a model of glucose-insulin feedback system in the overnight-fasted state&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a> was shown to be a good predictor of CVD&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> This method has been widely used in clinical practice to measure IR&#44; however due to cost-effectiveness and the instability of insulin in blood&#44; the efficacy of HOMA-IR is questionable&#46; Thus&#44; for clinical practice a simple&#44; robust and accessible marker as a surrogate for IR to address this pathology and predict cardiovascular risk is needed&#46; Triglyceride-glucose index&#44; a product of fasting triglycerides &#40;TG&#41; and glucose&#44; and TG-to-high density lipoprotein cholesterol &#40;HDL&#41; ratio &#40;TG&#47;HDL&#41; have been more recently suggested as an alternative to measure IR with improved efficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">4</span></a> Moreover&#44; some anthropometric measurements&#44; such as body mass index &#40;BMI&#41; and waist circumference &#40;WC&#41;&#44; are also used to identify IR&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">5</span></a> However&#44; in the current issue&#44; Nunes et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> found that there was a better correlation between lipid accumulation product &#40;LAP&#41; and HOMA-IR than with BMI&#44; neck circumference &#40;NC&#41;&#44; waist-hip ratio &#40;WHR&#41; and sagittal abdominal diameter &#40;SAD&#41;&#44; in elderly population&#46; Although these measurements are easy to obtain&#44; anthropometric measurements are not comprehensive in reflecting obesity and metabolic abnormalities for each individual&#46; In this scenario&#44; LAP emerges as a result of the correlation between waist measurements and fasting TG levels&#44; thus reflecting both anatomic and physiological alterations related to lipid accumulation&#46; The authors therefore suggest LAP as a useful and simple clinical marker to assess cardiometabolic risk factors&#46; Indeed&#44; in a cross-sectional study including non-diabetic subjects&#44; LAP was found to be closely associated with HOMA-IR&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> Recent studies have also corroborated the direct correlation between LAP and IR&#44; as well as increased incidence of CVD&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">8&#44;9</span></a> Thus&#44; LAP&#44; a single and inexpensive index&#44; has been suggested as a precise marker that outperforms BMI and WC in identifying IR in a large population range&#44; showing a strong association with CVD risk factors&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Considering the close association between LAP&#44; diabetes and metabolic syndrome&#44; and the fact that this index takes into account TG circulating levels&#44; it is expected to be strongly correlated with an altered circulating lipid profile&#46; Recent studies report that higher LAP is related to abnormal total cholesterol&#44; high density lipoprotein cholesterol &#40;HDL-C&#41; levels&#44; TG to HDL-C ratio and malondialdehyde&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">10</span></a> Similar results were obtained in the study by Nunes et al&#46;&#44; where a positive correlation between low levels of HDL-C as well as high levels of TG and increased levels of LAP was demonstrated&#46; Thus&#44; to gain a deeper knowledge of the etiology of metabolic disorders&#44; considerable efforts have been made to shift CVD research toward the study of dysregulated lipid metabolism by characterizing the circulating lipidome&#46; Very recent data showed&#44; through plasma lipidomic profiling via liquid chromatography-tandem mass spectrometry&#44; that lysoglycerophospholipids and sphingolipids are good lipid biomarkers associated with metabolic risk factors and consequent good biomarkers for CVD&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a> Moreover&#44; work carried out in the Strong Heart Family Study &#40;SHFS&#41;&#44; a well-characterized cohort study conducted in a population at high risk of diabetes&#44; demonstrated that higher levels of plasma ceramides were associated with higher fasting plasma insulin and HOMA-IR&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">12</span></a> Accordingly&#44; due to the complex phenotype and dynamics of chronic metabolic-related diseases&#44; affected by multiple genetic and environmental factors&#44; scientific and clinical communities have made efforts to find the molecular etiology behind these diseases&#46; In this scenario&#44; metabolomics appears as a powerful phenotyping tool&#44; which is described as a comprehensive analysis of all small molecules present in a biological system&#46; These types of approach provide an integrated view of the metabolic profiles due to the sensitive detection of molecular changes over time as result of intrinsic and extrinsic factors&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a> Thus&#44; metabolites&#44; as single molecules or integrated in a comprehensive signature&#44; are promising targets for efficient diagnosis&#44; prognosis and therapeutic approaches&#44; to overcome the limitation of the current conventional clinical markers during risk assessment and stratification&#46; The application of this technology can therefore contribute to decipher molecular mechanisms underlying metabolic diseases&#46; In line with this&#44; recent results obtained from machine learning classifiers&#44; based on the plasma lipidomes&#44; enabled the accurate distinction between different atherosclerosis-related CVD&#44; including ischemic stroke and systemic lupus erythematosus&#44; based on the lipid profile&#46; Notably&#44; this tool was also sensitive to statin treatment&#44; showing a distinct lipid fingerprint from the CVD cohorts&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In conclusion&#44; the work developed by Nunes et al&#46; has contributed to the field of metabolic disorder diagnosis&#44; such as IR&#44; revealing the LAP measurement as a valuable tool for the assessment of IR&#46; Moreover&#44; due to its tight correlation with CVD&#44; this marker can predict cardiometabolism risk in elderly population&#44; thus paving the way for the development of alternative methodologies to accurately measure the odds of cardiovascular events&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0020" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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Editorial comment
Insulin resistance as a predictor of cardiovascular diseases
Resistência à insulina como preditivo das doenças cardiovasculares
Neuza Dominguesa,b,c
a University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal
b University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal
c Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Despite improvements in cardiovascular diseases &#40;CVD&#41; diagnosis and treatment&#44; continuous aging and the sedentary lifestyle of modern societies have led to an increased incidence of heart and blood vessels diseases&#46; The World Health Organization estimates that CVDs account for 31&#37; of all global deaths&#44; increasing to over 50&#37; mortality among individuals with diabetes mellitus&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">1</span></a> This chronic state of hyperglycemia is normally associated with defects in insulin secretion and insulin action&#44; also known as insulin resistance &#40;IR&#41;&#44; or both&#46; Moreover&#44; defects in uptake and oxidation of glucose&#44; glycogen synthesis&#44; and in the ability to suppress lipid oxidation are some of the metabolic alterations due to the IR state&#46; These metabolic events consequently trigger oxidative stress and inflammatory responses that ultimately lead to cell damage&#46; Thus&#44; in hyperglycemia and IR states&#44; metabolic&#44; structural and functional alterations have been shown to affect multiple tissues&#44; including the heart&#44; skeletal muscle&#44; liver&#44; and adipose tissue&#46; In the heart and vasculature&#44; the aforementioned IR-induced changes have been associated with the incidence of diabetic cardiomyopathy&#44; coronary artery disease&#44; myocardial ischemia&#44; and ultimately heart failure&#46; Despite this strong link between IR and increased CVD incidence&#44; the proportion of CVD that can be attributed to IR remains unclear&#46; Through a meta-analysis&#44; IR measured using the homeostasis model assessment &#40;HOMA&#41;&#44; a model of glucose-insulin feedback system in the overnight-fasted state&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">2</span></a> was shown to be a good predictor of CVD&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">3</span></a> This method has been widely used in clinical practice to measure IR&#44; however due to cost-effectiveness and the instability of insulin in blood&#44; the efficacy of HOMA-IR is questionable&#46; Thus&#44; for clinical practice a simple&#44; robust and accessible marker as a surrogate for IR to address this pathology and predict cardiovascular risk is needed&#46; Triglyceride-glucose index&#44; a product of fasting triglycerides &#40;TG&#41; and glucose&#44; and TG-to-high density lipoprotein cholesterol &#40;HDL&#41; ratio &#40;TG&#47;HDL&#41; have been more recently suggested as an alternative to measure IR with improved efficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">4</span></a> Moreover&#44; some anthropometric measurements&#44; such as body mass index &#40;BMI&#41; and waist circumference &#40;WC&#41;&#44; are also used to identify IR&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">5</span></a> However&#44; in the current issue&#44; Nunes et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">6</span></a> found that there was a better correlation between lipid accumulation product &#40;LAP&#41; and HOMA-IR than with BMI&#44; neck circumference &#40;NC&#41;&#44; waist-hip ratio &#40;WHR&#41; and sagittal abdominal diameter &#40;SAD&#41;&#44; in elderly population&#46; Although these measurements are easy to obtain&#44; anthropometric measurements are not comprehensive in reflecting obesity and metabolic abnormalities for each individual&#46; In this scenario&#44; LAP emerges as a result of the correlation between waist measurements and fasting TG levels&#44; thus reflecting both anatomic and physiological alterations related to lipid accumulation&#46; The authors therefore suggest LAP as a useful and simple clinical marker to assess cardiometabolic risk factors&#46; Indeed&#44; in a cross-sectional study including non-diabetic subjects&#44; LAP was found to be closely associated with HOMA-IR&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> Recent studies have also corroborated the direct correlation between LAP and IR&#44; as well as increased incidence of CVD&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">8&#44;9</span></a> Thus&#44; LAP&#44; a single and inexpensive index&#44; has been suggested as a precise marker that outperforms BMI and WC in identifying IR in a large population range&#44; showing a strong association with CVD risk factors&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Considering the close association between LAP&#44; diabetes and metabolic syndrome&#44; and the fact that this index takes into account TG circulating levels&#44; it is expected to be strongly correlated with an altered circulating lipid profile&#46; Recent studies report that higher LAP is related to abnormal total cholesterol&#44; high density lipoprotein cholesterol &#40;HDL-C&#41; levels&#44; TG to HDL-C ratio and malondialdehyde&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">10</span></a> Similar results were obtained in the study by Nunes et al&#46;&#44; where a positive correlation between low levels of HDL-C as well as high levels of TG and increased levels of LAP was demonstrated&#46; Thus&#44; to gain a deeper knowledge of the etiology of metabolic disorders&#44; considerable efforts have been made to shift CVD research toward the study of dysregulated lipid metabolism by characterizing the circulating lipidome&#46; Very recent data showed&#44; through plasma lipidomic profiling via liquid chromatography-tandem mass spectrometry&#44; that lysoglycerophospholipids and sphingolipids are good lipid biomarkers associated with metabolic risk factors and consequent good biomarkers for CVD&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a> Moreover&#44; work carried out in the Strong Heart Family Study &#40;SHFS&#41;&#44; a well-characterized cohort study conducted in a population at high risk of diabetes&#44; demonstrated that higher levels of plasma ceramides were associated with higher fasting plasma insulin and HOMA-IR&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">12</span></a> Accordingly&#44; due to the complex phenotype and dynamics of chronic metabolic-related diseases&#44; affected by multiple genetic and environmental factors&#44; scientific and clinical communities have made efforts to find the molecular etiology behind these diseases&#46; In this scenario&#44; metabolomics appears as a powerful phenotyping tool&#44; which is described as a comprehensive analysis of all small molecules present in a biological system&#46; These types of approach provide an integrated view of the metabolic profiles due to the sensitive detection of molecular changes over time as result of intrinsic and extrinsic factors&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">11</span></a> Thus&#44; metabolites&#44; as single molecules or integrated in a comprehensive signature&#44; are promising targets for efficient diagnosis&#44; prognosis and therapeutic approaches&#44; to overcome the limitation of the current conventional clinical markers during risk assessment and stratification&#46; The application of this technology can therefore contribute to decipher molecular mechanisms underlying metabolic diseases&#46; In line with this&#44; recent results obtained from machine learning classifiers&#44; based on the plasma lipidomes&#44; enabled the accurate distinction between different atherosclerosis-related CVD&#44; including ischemic stroke and systemic lupus erythematosus&#44; based on the lipid profile&#46; Notably&#44; this tool was also sensitive to statin treatment&#44; showing a distinct lipid fingerprint from the CVD cohorts&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In conclusion&#44; the work developed by Nunes et al&#46; has contributed to the field of metabolic disorder diagnosis&#44; such as IR&#44; revealing the LAP measurement as a valuable tool for the assessment of IR&#46; Moreover&#44; due to its tight correlation with CVD&#44; this marker can predict cardiometabolism risk in elderly population&#44; thus paving the way for the development of alternative methodologies to accurately measure the odds of cardiovascular events&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0020" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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