Plasma metabolite profile of legume consumption and future risk of type 2 diabetes and cardiovascular disease

Journal of Clinical Medicine

Background: Lifestyles influence atrial fibrillation (AF) risk. Determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways could help understand AF pathophysiology and contribute to AF prevention. Methods: We studied 532 participants enrolled in the PREDIMED-Plus trial, a Spanish randomized trial conducted in adults (55–75 years) with metabolic syndrome and body mass index between 27–40 kg/m2. Eligible participants were randomized 1:1 to an intensive lifestyle intervention, emphasizing physical activity, weight loss, and adherence to an energy-reduced Mediterranean diet or to a control group. Serum biomarkers [carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)] were measured at baseline, 3 and 5 years after randomization. Mixed models were used to evaluate the effect of intervention on changes in biomarkers through year 5. Mediation analysis was performed to examine the proportion mediated by each component of the intervention. Results: At baseline, participants’ mean age was 65, 40% were female, and 50% were assigned to the intervention. After five years, mean changes in log-transformed biomarkers were −0.01 (PICP), 0.20 (hsTnT), −0.17 (hsCRP), 0.12 (3-NT), and 0.27 (NT-proBNP). Compared to the control group, participants in the intervention group experienced greater decreases in hsCRP (−14%, 95% confidence interval (CI) −26%, 0%) or smaller increases in 3-NT (−16%, 95% CI −25%, −5 …

Diabetes Care

OBJECTIVE Breastfeeding duration is inversely associated with risks of cardiovascular disease (CVD) and type 2 diabetes in parous women. However, the association among women at high risk, including women with type 2 diabetes or gestational diabetes (GDM) is unclear. RESEARCH DESIGN AND METHODS We included 15,146 parous women with type 2 diabetes from the Nurses’ Health Study I and II (NHS, NHS II) and 4,537 women with a history of GDM from NHS II. Participants reported history of breastfeeding via follow-up questionnaires. Incident CVD by 2017 comprised stroke or coronary heart disease (CHD: myocardial infarction, coronary revascularization). Adjusted hazard ratios (aHRs) and 95% CIs were estimated using Cox models. RESULTS We documented 1,159 incident CVD cases among women with type 2 diabetes in both cohorts during …

Metabolism

BackgroundMetabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion.MethodsThe study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was …

Clinical Pediatrics

Dr. Lester F. Soyka: E. M., a 13-year-old girl, was referred to the Massachusetts General Hospital because of uncontrolled hyper-tension. She was in apparent good health until four years ago when she had an episode of dysuria and pyuria diagnosed as cystitis and treated with Furadantin. She had two subsequent attacks three years ago and one year ago similarly treated. She seemed well until six weeks prior to admission when gross hematuria developed with no associated symptoms and no previous history of recent upper respiratory infection. Penicillin was started. In the next few days she developed headache, abdominal cramps, and anorexia. On admission to another hospital it was found that her blood pressure was 270/190, there was marked arteriolar spasm on funduscopy, and her urine was loaded with red and white blood cells with no casts. Intravenous and retrograde pyelography showed a shrunken …

Healthy blood vessels supply neurons to preserve metabolic function. In blinding proliferative retinopathies (PRs), pathological neovascular tufts often emerge in lieu of needed physiological revascularization of the ischemic neuroretina. Here we show that metabolic shifts in the neurovascular niche define angiogenic fate. Fatty acid oxidation (FAO) metabolites accumulated in human and murine retinopathy samples. Neovascular tufts with a distinct single-cell transcriptional signature highly expressed FAO enzymes. The deletion of Sirt3, an FAO regulator, shifted the neurovascular niche metabolism from FAO to glycolysis and suppressed tuft formation. This metabolic transition increased Vegf expression in astrocytes and reprogrammed pathological EC to a physiological phenotype, hastening vascular regeneration of the ischemic retina. Hence, strategies to change the metabolic environment of vessels could promote a regenerative phenotype in vascular diseases.

Metabolism

BackgroundMetabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion.MethodsThe study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was …

Environment International

Los disruptores endocrinos (DE) se han convertido en posibles contribuyentes al desarrollo de la diabetes tipo 2. El sulfonato de perfluorooctano (PFOS) es uno de estos DE vinculados con enfermedades crónicas y que atrajo atención debido a su presencia generalizada en los alimentos. Objetivo Evaluar al inicio y después de 1 año de seguimiento las asociaciones entre la ingesta dietética estimada (DI) de PFOS y los parámetros de homeostasis de la glucosa y el índice de masa corporal (IMC) en una población de personas mayores de 4600 participantes no diabéticos del PREDIMED. -más estudio. Métodos Se realizaron modelos de regresión lineal multivariable para evaluar las asociaciones entre el valor inicial de PFOS-DI en el límite inferior (LB) y el límite superior (UB) establecidos por la EFSA, los parámetros de homeostasis de la glucosa y el IMC. Resultados En comparación con aquellos en el tercil más bajo, los participantes en el tercil más alto de PFOS-DI inicial en LB y UB mostraron niveles más altos de HbA1c [coeficiente β (CI)] [0,01 % (0,002 a 0,026) y [0,06 mg/dL (0,026 a 0,087), ambas tendencia p ≤ 0,001] y glucosa plasmática en ayunas en el LB PFOS-DI [1,05 mg/dL (0,050 a 2,046), tendencia p = 0,022]. Prospectivamente, se demostró una asociación positiva entre el LB de PFOS-DI y el IMC [0,06 kg/m 2 (0,014 a 0,106) por incremento de 1 DE de PFOS-DI ajustado en función de la energía. Los participantes en el tercil superior mostraron un aumento en HOMA-IR [0,06 (0,016 a 0,097), tendencia p = 0,005] en comparación con los participantes en el tercil de referencia después de 1 año de seguimiento. Discusión …

EBioMedicine

BackgroundLung function trajectories (LFTs) have been shown to be an important measure of long-term health in asthma. While there is a growing body of metabolomic studies on asthma status and other phenotypes, there are no prospective studies of the relationship between metabolomics and LFTs or their genomic determinants.MethodsWe utilized ordinal logistic regression to identify plasma metabolite principal components associated with four previously-published LFTs in children from the Childhood Asthma Management Program (CAMP) (n = 660). The top significant metabolite principal component (PCLF) was evaluated in an independent cross-sectional child cohort, the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) (n = 1151) and evaluated for association with spirometric measures. Using meta-analysis of CAMP and GACRS, we identified associations between PCLF and microRNA, and …

Journal of Allergy and Clinical Immunology

BackgroundThere are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations.ObjectiveWe sought to identify metabolites unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort, the Boston Birth Cohort.MethodsMass spectrometry–based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (n = 811). FA was diagnosed according to clinical symptoms consistent with an acute hypersensitivity reaction at food ingestion and food specific-IgE > 0.35 kU/L. Asthma was defined on the basis of physician diagnosis. Generalized estimating equations were applied to analyze metabolomic associations with FA and asthma, adjusting for potential confounders.ResultsDuring a …

EClinicalMedicine

BackgroundUltra-processed foods (UPFs) are emerging as a risk factor for colorectal cancer (CRC), yet how post-diagnostic UPF intake may impact CRC prognosis remains unexplored.MethodsData collected from food frequency questionnaires were used to estimate intakes of total UPFs and UPF subgroups (serving/d) at least 6 months but less than 4 years post-diagnosis among 2498 patients diagnosed with stages I–III CRC within the Nurses' Health Study and Health Professionals Follow-up Study during 1980–2016. Hazard ratios (HR) and 95% confidence intervals (CIs) of all-cause, CRC- and cardiovascular disease (CVD)-specific mortality in association with UPF consumption were estimated using an inverse probability weighted multivariable Cox proportional hazards regression model, adjusted for confounders.FindingsThe mean (SD) age of patients at diagnosis was 68.5 (9.4) years. A total of 1661 deaths …

The American Journal of Clinical Nutrition

BackgroundThe health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood.ObjectivesOur goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors.MethodsA total of 400 participants (200 from each study group), aged 55–75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry …

Journal of Allergy and Clinical Immunology

MethodsUntargeted metabolomic profiling was conducted on plasma samples from 4 timepoints during a longitudinal peanut OIT interventional trial in children ages 7-18. After OIT, participants were challenged before and after a 4-week avoidance period and categorized as either having persistent protection (sustained unresponsiveness (SU)) or loss of protection (transient desensitization (TD)). Using linear and logistic regression and time series analyses, we identified changes in metabolites and pathways associated with (1) OIT over time, and (2) differences between SU and TD participants.ResultsWe identified decreases in arachidonic acid (p= 1.3 e-23) and linoleic acid (p= 1.0 e-04) pathways during OIT. Comparing SU versus TD revealed differing concentrations of bile acid (p= 3.7 e-08), arachidonic acid (p= 3.2 e-09), and histidine pathways. Notably, the bile acid metabolite, lithocholate (3.48 [1.53, 9.24], p …

Communications Biology

Type 2 diabetes (T2D) is known as one of the important risk factors for the severity and mortality of COVID-19. Here, we evaluate the impact of T2D and its genetic susceptibility on the severity and mortality of COVID-19, using 459,119 individuals in UK Biobank. Utilizing the polygenic risk scores (PRS) for T2D, we identified a significant association between T2D or T2D PRS, and COVID-19 severity. We further discovered the efficacy of vaccination and the pivotal role of T2D-related genetics in the pathogenesis of severe COVID-19. Moreover, we found that individuals with T2D or those in the high T2D PRS group had a significantly increased mortality rate. We also observed that the mortality rate for SARS-CoV-2-infected patients was approximately 2 to 7 times higher than for those not infected, depending on the time of infection. These findings emphasize the potential of T2D PRS in estimating the severity and …

Cell Metabolism

Common genetic variants in glucokinase regulator (GCKR), which encodes GKRP, a regulator of hepatic glucokinase (GCK), influence multiple metabolic traits in genome-wide association studies (GWASs), making GCKR one of the most pleiotropic GWAS loci in the genome. It is unclear why. Prior work has demonstrated that GCKR influences the hepatic cytosolic NADH/NAD+ ratio, also referred to as reductive stress. Here, we demonstrate that reductive stress is sufficient to activate the transcription factor ChREBP and necessary for its activation by the GKRP-GCK interaction, glucose, and ethanol. We show that hepatic reductive stress induces GCKR GWAS traits such as increased hepatic fat, circulating FGF21, and circulating acylglycerol species, which are also influenced by ChREBP. We define the transcriptional signature of hepatic reductive stress and show its upregulation in fatty liver disease and …

medRxiv

Aims To explore the associations between breakfast energy intake and quality and time trajectories of cardiometabolic traits in high cardiovascular risk. Methods 383 participants aged 55-75 from the PREDIMED-Plus cohort were included. Longitudinal averages of breakfast energy intake and quality were calculated. Three categories were defined for energy intake: 20-30% (reference), <20% (low), and >30% (high). Quality was estimated using the Meal Balance Index; categories were above (reference) or below the median score (low). Smoothed cubic spline mixed effects regressions described trajectories of cardiometabolic indicators (anthropometry, blood pressure, lipids, glucose, glycated hemoglobin, and estimated glomerular filtration rate) at breakfast groups. Inter-group differences in predicted values were estimated by linear regressions. Results At 36 months, compared to the reference, low- or high-energy breakfasts were associated with differences in: body mass index (low: 0.62 kg/m2 [95% confidence interval: 0.28; 0.96]; high: 1.17 kg/m2 [0.79; 1.56]), waist circumference (low: 2.24 cm [1.16; 3.32]; high: 4.55 cm [3.32; 5.78]), triglycerides (low: 18.3 mg/dL [15.3; 21.4]; high: 34.5 cm [31.0; 38.1]), and HDL cholesterol (low: -2.13 mg/dL [-3.40; -0.86]; high: -4.56 mg/dL [-6.02; -3.10]). At 36 months, low-quality breakfast was associated with higher waist circumference (1.49 cm [0.67; 2.31]), and triglycerides (3.46 mg/dL [1.13; 5.80]) and less HDL cholesterol (-1.65 mg/dL [-2.61; -0.69]) and glomerular filtration rate (-1.21 mL/min/1.73m2 [-2.01; -0.41]). Conclusions Low- or high-energy and low-quality breakfasts were associated with higher …

Cancer Research

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all cancer types. A key — yet poorly understood — facet in the disease state is cachexia, a multi-organ pathological state characterized by physical wasting and tissue catabolism. It occurs in 80% of PDAC patients, and to date there are no preventative or early detection methods. Cachexia leads to limited tolerance to anti-cancer therapy and contributes to disease lethality. Here, we present the first-of-its-kind systemic metabolomic analysis across cachectic stages to better understand disease progression. We used the well-established mutant KRASG12D(LSL/+) mutant p53 inducible mouse model of PDAC. Model physiology faithfully recaptures human cachexia: we observe progressive overall weight loss as well as loss of skeletal muscle and adipose tissue. As with human disease, weight loss occurs prior to loss of appetite in the animals …

Metabolism

BackgroundMetabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion.MethodsThe study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was …

The American Journal of Clinical Nutrition

BackgroundThe health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood.ObjectivesOur goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors.MethodsA total of 400 participants (200 from each study group), aged 55–75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry …

Public Health

ObjectiveThis article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD).MethodsBaseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models.ResultsAfter one year of intervention, the kcal/day consumed was …

The American Journal of Clinical Nutrition

BackgroundDistinct circulating bile acid (BA) subtypes may play roles in regulating lipid homeostasis and atherosclerosis.ObjectivesWe investigated whether changes in circulating BA subtypes induced by weight-loss dietary interventions were associated with improved lipid profiles and atherosclerotic cardiovascular disease (ASCVD) risk estimates.MethodsThis study included adults with overweight or obesity (n=536) who participated in a randomized weight-loss diet intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 months after weight-loss diet interventions. The ASCVD risk estimates were calculated by the validated equations.ResultsAt baseline, higher levels of specific BA subtypes were related to higher levels of atherogenic VLDL lipid subtypes and ASCVD risk estimates. Weight-loss diet-induced decreases in …

Cardiovascular diabetology

BackgroundIn this study, we evaluated the lipidome alterations caused by type 1 diabetes (T1D) and type 2 diabetes (T2D), by determining lipids significantly associated with diabetes overall and in both sexes, and lipids associated with the glycaemic state.MethodsAn untargeted lipidomic analysis was performed to measure the lipid profiles of 360 subjects (91 T1D, 91 T2D, 74 with prediabetes and 104 controls (CT)) without cardiovascular and/or chronic kidney disease. Ultra-high performance liquid chromatography-electrospray ionization mass spectrometry (UHPLC-ESI-MS) was conducted in two ion modes (positive and negative). We used multiple linear regression models to (1) assess the association between each lipid feature and each condition, (2) determine sex-specific differences related to diabetes, and (3) identify lipids associated with the glycaemic state by considering the prediabetes stage. The …

Cardiovascular Diabetology

BackgroundType 2 diabetes (T2D) and peripheral artery disease (PAD) are recognized as independent risk factors contributing to excess mortality. Contemporary observational studies exploring the associations of risk factors, and risk of all-cause and atherosclerotic cardiovascular disease mortality in persons with T2D following the onset of incident peripheral artery disease are limited. The objectives of this study were to investigate the associations of risk factors, and assess mortality risks in people with T2D compared with controls without T2D after the onset of PAD.MethodsAll persons with T2D (n = 150,215) registered in the Swedish National Diabetes Register between 2005 and 2009 were included, along with 346,423 controls without T2D matched for sex and age. Data were retrieved from several national registries, capturing information on risk factors, onset of incident peripheral artery disease, other …

Cardiovascular Diabetology

BackgroundGestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) share many pathophysiological factors including genetics, but whether epigenetic marks are shared is unknown. We aimed to test whether a DNA methylation risk score (MRS) for T2DM was associated with GDM across ancestry and GDM criteria.MethodsIn two independent pregnancy cohorts, EPIPREG (n = 480) and EPIDG (n = 32), DNA methylation in peripheral blood leukocytes was measured at a gestational age of 28 ± 2. We constructed an MRS in EPIPREG and EPIDG based on CpG hits from a published epigenome-wide association study (EWAS) of T2DM.ResultsWith mixed models logistic regression of EPIPREG and EPIDG, MRS for T2DM was associated with GDM: odd ratio (OR)[95% CI]: 1.3 [1.1–1.8], P = 0.002 for the unadjusted model, and 1.4 [1.1–1.7], P = 0.00014 for a model adjusted by age, pre …

Cardiovascular diabetology

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD …

Cardiovascular Diabetology

BackgroundTissue-specific insulin resistance (IR) predominantly in muscle (muscle IR) or liver (liver IR) has previously been linked to distinct fasting metabolite profiles, but postprandial metabolite profiles have not been investigated in tissue-specific IR yet. Given the importance of postprandial metabolic impairments in the pathophysiology of cardiometabolic diseases, we compared postprandial plasma metabolite profiles in response to a high-fat mixed meal between individuals with predominant muscle IR or liver IR.MethodsThis cross-sectional study included data from 214 women and men with BMI 25–40 kg/m2, aged 40–75 years, and with predominant muscle IR or liver IR. Tissue-specific IR was assessed using the muscle insulin sensitivity index (MISI) and hepatic insulin resistance index (HIRI), which were calculated from the glucose and insulin responses during a 7-point oral glucose tolerance test. Plasma …

Cardiovascular Diabetology

Diabetes mellitus is a chronic disease which is detrimental to cardiovascular health, often leading to secondary microvascular complications, with huge global health implications. Therapeutic interventions that can be applied to multiple vascular beds are urgently needed. Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are characterised by early microvascular permeability changes which, if left untreated, lead to visual impairment and renal failure, respectively. The heparan sulphate cleaving enzyme, heparanase, has previously been shown to contribute to diabetic microvascular complications, but the common underlying mechanism which results in microvascular dysfunction in conditions such as DR and DKD has not been determined. In this study, two mouse models of heparan sulphate depletion (enzymatic removal and genetic ablation by endothelial specific Exotosin-1 knock down) were utilized …

Cardiovascular Diabetology

BackgroundAsialoglycoprotein receptor 1 (ASGR1), primarily expressed on hepatocytes, promotes the clearance and the degradation of glycoproteins, including lipoproteins, from the circulation. In humans, loss-of-function variants of ASGR1 are associated with a favorable metabolic profile and reduced incidence of cardiovascular diseases. The molecular mechanisms by which ASGR1 could affect the onset of metabolic syndrome and obesity are unclear. Therefore, here we investigated the contribution of ASGR1 in the development of metabolic syndrome and obesity.MethodsASGR1 deficient mice (ASGR1−/−) were subjected to a high-fat diet (45% Kcal from fat) for 20 weeks. The systemic metabolic profile, hepatic and visceral adipose tissue were characterized for metabolic and structural alterations, as well as for immune cells infiltration.ResultsASGR1−/− mice present a hypertrophic adipose tissue with 41 …

Cardiovascular Diabetology

BackgroundSodium-glucose co-transporter 2 inhibitors (SGLT2i) have been suggested to exert cardioprotective effects in patients with heart failure, possibly by improving the metabolism of ketone bodies in the myocardium.MethodsThis post hoc analysis of the EMMY trial investigated the changes in serum β-hydroxybutyrate (3-βOHB) levels after acute myocardial infarction (AMI) in response to 26-week of Empagliflozin therapy compared to the usual post-MI treatment. In addition, the association of baseline and repeated measurements of 3-βOHB with cardiac parameters and the interaction effects of Empagliflozin were investigated. Cardiac parameters included N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), left ventricle end-systolic volume (LVESV), left ventricle end-diastolic volume (LVEDV), and left ventricular filling pressure (E/é ratio).ResultsThe mean 3-βOHB …

Cardiovascular diabetology

BackgroundIn this study, we evaluated the lipidome alterations caused by type 1 diabetes (T1D) and type 2 diabetes (T2D), by determining lipids significantly associated with diabetes overall and in both sexes, and lipids associated with the glycaemic state.MethodsAn untargeted lipidomic analysis was performed to measure the lipid profiles of 360 subjects (91 T1D, 91 T2D, 74 with prediabetes and 104 controls (CT)) without cardiovascular and/or chronic kidney disease. Ultra-high performance liquid chromatography-electrospray ionization mass spectrometry (UHPLC-ESI-MS) was conducted in two ion modes (positive and negative). We used multiple linear regression models to (1) assess the association between each lipid feature and each condition, (2) determine sex-specific differences related to diabetes, and (3) identify lipids associated with the glycaemic state by considering the prediabetes stage. The …

Cardiovascular Diabetology

BackgroundAsialoglycoprotein receptor 1 (ASGR1), primarily expressed on hepatocytes, promotes the clearance and the degradation of glycoproteins, including lipoproteins, from the circulation. In humans, loss-of-function variants of ASGR1 are associated with a favorable metabolic profile and reduced incidence of cardiovascular diseases. The molecular mechanisms by which ASGR1 could affect the onset of metabolic syndrome and obesity are unclear. Therefore, here we investigated the contribution of ASGR1 in the development of metabolic syndrome and obesity.MethodsASGR1 deficient mice (ASGR1−/−) were subjected to a high-fat diet (45% Kcal from fat) for 20 weeks. The systemic metabolic profile, hepatic and visceral adipose tissue were characterized for metabolic and structural alterations, as well as for immune cells infiltration.ResultsASGR1−/− mice present a hypertrophic adipose tissue with 41 …

Cardiovascular Diabetology

BackgroundThe stress hyperglycemia ratio (SHR) has been demonstrated as an independent risk factor for acute kidney injury (AKI) in certain populations. However, this relationship in patients with congestive heart failure (CHF) remains unclear. Our study sought to elucidate the relationship between SHR and AKI in patients with CHF.MethodsA total of 8268 patients with CHF were included in this study. We categorized SHR into distinct groups and evaluated its association with mortality through logistic or Cox regression analyses. Additionally, we applied the restricted cubic spline (RCS) analysis to explore the relationship between SHR as a continuous variable and the occurrence of AKI. The primary outcome of interest in this investigation was the incidence of AKI during hospitalization.ResultsWithin this patient cohort, a total of 5,221 (63.1%) patients experienced AKI during their hospital stay. Upon adjusting for …

Cardiovascular diabetology

BackgroundLegume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD.MethodsThe current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 …

Cardiovascular Diabetology

BackgroundIntensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown whether Hp phenotype modifies the effect of an intensive lifestyle intervention (ILI) on CAD in type 2 diabetes.MethodsHaptoglobin phenotype was measured in 4542 samples from the Action for Health in Diabetes (Look AHEAD) study. Cox regression models assessed the effect of ILI (focused on weight loss from caloric restriction and physical activity) versus diabetes support and education (DSE) on CAD events in each phenotype group, and within pre-specified subgroups including race/ethnicity, sex, history of cardiovascular disease, diabetes medication use, and diabetes duration.Results1590 (35%) participants had the Hp2-2 phenotype. The ILI did not lower glycated …

Cardiovascular diabetology

BackgroundIn this study, we evaluated the lipidome alterations caused by type 1 diabetes (T1D) and type 2 diabetes (T2D), by determining lipids significantly associated with diabetes overall and in both sexes, and lipids associated with the glycaemic state.MethodsAn untargeted lipidomic analysis was performed to measure the lipid profiles of 360 subjects (91 T1D, 91 T2D, 74 with prediabetes and 104 controls (CT)) without cardiovascular and/or chronic kidney disease. Ultra-high performance liquid chromatography-electrospray ionization mass spectrometry (UHPLC-ESI-MS) was conducted in two ion modes (positive and negative). We used multiple linear regression models to (1) assess the association between each lipid feature and each condition, (2) determine sex-specific differences related to diabetes, and (3) identify lipids associated with the glycaemic state by considering the prediabetes stage. The …

Cardiovascular Diabetology

BackgroundAsialoglycoprotein receptor 1 (ASGR1), primarily expressed on hepatocytes, promotes the clearance and the degradation of glycoproteins, including lipoproteins, from the circulation. In humans, loss-of-function variants of ASGR1 are associated with a favorable metabolic profile and reduced incidence of cardiovascular diseases. The molecular mechanisms by which ASGR1 could affect the onset of metabolic syndrome and obesity are unclear. Therefore, here we investigated the contribution of ASGR1 in the development of metabolic syndrome and obesity.MethodsASGR1 deficient mice (ASGR1−/−) were subjected to a high-fat diet (45% Kcal from fat) for 20 weeks. The systemic metabolic profile, hepatic and visceral adipose tissue were characterized for metabolic and structural alterations, as well as for immune cells infiltration.ResultsASGR1−/− mice present a hypertrophic adipose tissue with 41 …

Cardiovascular diabetology

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD …

Cardiovascular Diabetology

BackgroundTissue-specific insulin resistance (IR) predominantly in muscle (muscle IR) or liver (liver IR) has previously been linked to distinct fasting metabolite profiles, but postprandial metabolite profiles have not been investigated in tissue-specific IR yet. Given the importance of postprandial metabolic impairments in the pathophysiology of cardiometabolic diseases, we compared postprandial plasma metabolite profiles in response to a high-fat mixed meal between individuals with predominant muscle IR or liver IR.MethodsThis cross-sectional study included data from 214 women and men with BMI 25–40 kg/m2, aged 40–75 years, and with predominant muscle IR or liver IR. Tissue-specific IR was assessed using the muscle insulin sensitivity index (MISI) and hepatic insulin resistance index (HIRI), which were calculated from the glucose and insulin responses during a 7-point oral glucose tolerance test. Plasma …

Cardiovascular Diabetology

ImportanceDiabetes mellitus (DM) is thought to be closely related to arterial stenotic or occlusive disease caused by atherosclerosis. However, there is still no definitive clinical evidence to confirm that patients with diabetes have a higher risk of restenosis.ObjectiveThis meta-analysis was conducted to determine the effect of DM on restenosis among patients undergoing endovascular treatment, such as percutaneous transluminal angioplasty (PTA) or stenting.Data sources and study selectionThe PubMed/Medline, EMBASE and Cochrane Library electronic databases were searched from 01/1990 to 12/2022, without language restrictions. Trials were included if they satisfied the following eligibility criteria: (1) RCTs of patients with or without DM; (2) lesions confined to the coronary arteries or femoral popliteal artery; (3) endovascular treatment via PTA or stenting; and (4) an outcome of restenosis at the target lesion …

Cardiovascular diabetology

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD …

Cardiovascular Diabetology

Since the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI. This single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 …