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Metabolites
Special Issues
Current Research in Metabolic Syndrome and Cardiometabolic Disorders
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Current Research in Metabolic Syndrome and Cardiometabolic Disorders

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: 15 August 2026 | Viewed by 4875

Special Issue Editors

Dr. Ciprian Ilie Rosca

E-Mail Website
Guest Editor
Internal Medicine I—Discipline of Medical Semiology I, Department V, Center of Advanced Research in Cardiology and Hemostasology, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania
Interests: atrial fibrillation; metabolic syndrome; stroke; dyslipidemia; endothelial dysfunction; heart failure; chronic coronary syndromes
Dr. Yunping Qiu

E-Mail Website
Guest Editor
The Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Albert Einstein College of Medicine, Bronx, NY 10461, USA
Interests: metabolomics; mass spectrometry; metabolites identification; biomarker discovery; stable isotope flux; cancer metabolism; infectious diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular disorders are considered to be a leading cause of a low quality of life (QOL), increased Disability-Adjusted Life Years (DALY), and rising mortality rates. The highly close link between cardiovascular disease and metabolic disorders has led to a rise in new research fields. Although metabolic syndrome is not a disease itself, its presence significantly increases the likelihood of comorbidities and ultimately increases the risk of cardiovascular major events, thereby leading to higher mortality rates. In recent years, the existence of the paradoxical effects related to obesity, total cholesterol, LDL cholesterol, and even for the metabolic syndrome have come to light.

This Special Issue aims to reveal new discoveries in the field of metabolic dysfunction and their impact on cardiovascular diseases. We invite papers focusing on evaluating the relationships between dyslipidemia, elevated uric acid levels, obesity, diabetes mellitus or pre-diabetes and cardiovascular diseases (heart failure, cardiac arrhythmias, chronic or acute coronary syndromes, arterial hypertension, but not limited). In addition to this, we also invite studies on other forms of metabolic dysfunctions, such as metabolic dysfunction-associated steatotic liver disease, FIB-4 score, or novel scores, alongside their association with heart disease. Studies focusing on the correlations between COVID-19, metabolic dysfunctions and cardiovascular disease are welcome as well. In the last few years, we experienced a therapeutic revolution, in which drugs designed for the treatment of diabetes mellitus showed a major impact on heart health, raising hopes in patients with heart failure. The effect of these drugs on the metabolic syndrome remains debatable and studies in this domain are of interest, as well as the epidemiological aspects of metabolic syndrome.

Submissions may be made online until 15 August 2026. All papers submitted will be pre-checked, and if suitable for publication, will undergo a peer-review process. If accepted, the paper will be published as soon as possible.

Dr. Ciprian Ilie Rosca
Dr. Yunping Qiu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolic syndrome
  • obesity
  • dyslipidemias
  • hyperuricemia
  • diabetes mellitus
  • cardiovascular diseases
  • heart failure
  • arrythmias
  • acute or chronic coronary syndromes
  • SGLT2-inhibitors
  • metabolic liver diseases
  • COVID-19 infection

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Published Papers (4 papers)

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Research

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18 pages, 686 KB  
Article
Triglyceride-to-HDL Cholesterol Ratio Is Associated with Ischemic Stroke Risk in Patients—With Paroxysmal Atrial Fibrillation
by Ciprian Ilie Rosca, Daniel Florin Lighezan, Doina Georgescu, Horia Silviu Branea, Nilima Rajpal Kundnani, Ariana Violeta Nicoras, Romina Georgiana Bita and Daniel Dumitru Nisulescu
Metabolites 2026, 16(2), 110; https://doi.org/10.3390/metabo16020110 - 3 Feb 2026
Viewed by 685
Abstract
Background: Ischemic stroke remains the most feared complication of atrial fibrillation (AF), and thromboembolic risk is commonly estimated using clinical scores that may not fully capture the cardiometabolic dimension of cerebrovascular vulnerability. The aim of this research was to assess whether additional parameters [...] Read more.
Background: Ischemic stroke remains the most feared complication of atrial fibrillation (AF), and thromboembolic risk is commonly estimated using clinical scores that may not fully capture the cardiometabolic dimension of cerebrovascular vulnerability. The aim of this research was to assess whether additional parameters can be used, to predict ischemic stroke risk in patients with AF, in order to explore whether TG/HDL-C may complement conventional clinical risk scores for ischemic stroke risk stratification in PAF, and to better characterize a metabolically high-risk phenotype beyond the recommendations provided by the CHA2DS2-VA score, which is useful but still far from perfect in predicting AF-associated ischemic stroke risk. Methods: In this retrospective, single-center observational study, we evaluated whether the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDLc), a simple surrogate of atherogenic dyslipidemia and insulin resistance, is associated with ischemic stroke risk in patients with paroxysmal atrial fibrillation (PAF). We screened 1111 consecutive AF admissions between 1 January 2015 and 31 December 2016 and, from these 1111 AF cases, we extracted only the patients with PAF for analysis. Patients were stratified based on TG/HDLc values into two groups, Group 1 (TG/HDLc > 2.5; n = 155) and Group 2 (TG/HDLc < 2.5; n = 194). Statistical analysis was performed with MedCalc v23.4.0 using Chi-square and unpaired/Welch’s t-tests as appropriate, Pearson correlations, Kaplan–Meier analysis with log-rank testing, Cox regression for first ischemic stroke, and multivariable logistic regression to identify independent correlates of TG/HDLc > 2.5. Results: Patients with TG/HDLc > 2.5 had a significantly higher prevalence of ischemic stroke after AF onset compared with those with TG/HDLc < 2.5 (37.4% vs. 21.1%, p = 0.0008), despite similar CHA2DS2-VA and HAS-BLED scores, and also exhibited a higher burden of cerebrovascular and neurodegenerative findings, including cortical atrophy and cerebral lacunarism. Ischemic stroke-free survival curves diverged significantly over time (log-rank p = 0.0186), and an elevated TG/HDLc ratio was associated with a 68% higher hazard of first ischemic stroke (HR 1.68; 95% CI 1.09–2.60). In multivariable analysis, type 2 diabetes mellitus (OR 4.53), hyperuricemia (OR 3.83), dyslipidemia (OR 1.94), stroke (OR 1.77), and cortical atrophy (OR 4.48) were independently associated with TG/HDLc > 2.5. Conclusions: These findings suggest that TG/HDLc identifies a metabolically high-risk PAF phenotype associated with greater cerebrovascular burden and reduced ischemic stroke-free survival, providing an inexpensive and broadly available marker that may complement conventional clinical risk scores. Full article
(This article belongs to the Special Issue Current Research in Metabolic Syndrome and Cardiometabolic Disorders)
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15 pages, 714 KB  
Article
Serum Calprotectin is Associated with Overweight and Laboratory Markers of Glucose Metabolism in Apparently Healthy Young Adults—A Cross-Sectional Descriptive Study
by Katarzyna Bergmann, Anna Stefańska, Magdalena Kuligowska-Prusińska and Magdalena Krintus
Metabolites 2025, 15(12), 756; https://doi.org/10.3390/metabo15120756 - 21 Nov 2025
Viewed by 870
Abstract
Background: Recent studies have indicated that serum calprotectin, a marker of inflammation, is associated with obesity and disorders of glucose and lipid metabolism. The aim of this study was to evaluate the relationship between serum calprotectin and cardiometabolic risk factors in presumably [...] Read more.
Background: Recent studies have indicated that serum calprotectin, a marker of inflammation, is associated with obesity and disorders of glucose and lipid metabolism. The aim of this study was to evaluate the relationship between serum calprotectin and cardiometabolic risk factors in presumably healthy young adults. Methods: The study enrolled 118 (61 females, 57 males) non-obese, normoglycemic, subjects aged 25–40 years, selected from the general population among participants of the diabetes preventive screening program in 2014–2015. Basic anthropometric measurements and the following laboratory tests were performed on all participants: glucose, glycated hemoglobin (HbA1c), lipid profile, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), high sensitivity C-reactive protein (hs-CRP), calprotectin and adiponectin. Results: The serum calprotectin concentration was significantly higher in men compared to women (p = 0.016), and in overweight subjects (p < 0.001) and those with abdominal obesity (p < 0.001), compared to lean individuals. Serum calprotectin was positively correlated with body mass index (BMI), waist circumference, HbA1c, hs-CRP, insulin, HOMA-IR and triglycerides, and negatively with HDL-cholesterol and adiponectin. In the univariable logistic regression analysis, overweight (OR = 2.529; p = 0.015), abdominal obesity (OR = 3.217; p = 0.006), hs-CRP > 1 mg/L (OR = 5.00; p < 0.001), HOMA-IR > 2.0 (OR = 4.394; p < 0.001), and HbA1c > 32 mmol/mol (OR = 2.166; p = 0.021) were significant predictors of increased calprotectin concentration (≥540.8 ng/mL; ≥median). However, in models adjusted for sex, BMI and hs-CRP, the significant association remained only for increased HbA1c and HOMA-IR values. Conclusions: Association of serum calprotectin with overweight, hs-CRP and laboratory indicators of glucose metabolism and insulin resistance suggest its significance as a laboratory biomarker of initial metabolic impairment. Full article
(This article belongs to the Special Issue Current Research in Metabolic Syndrome and Cardiometabolic Disorders)
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15 pages, 838 KB  
Article
Predictive Utility and Metabolomic Signatures of TG/HDL-C Ratio for Metabolic Syndrome Without Cardiovascular Disease and/or Diabetes in Qatari Adults
by Noora Kano, Najeha Anwardeen, Khaled Naja, Asma A. Elashi, Ahmed Malki and Mohamed A. Elrayess
Metabolites 2025, 15(9), 574; https://doi.org/10.3390/metabo15090574 - 28 Aug 2025
Cited by 2 | Viewed by 1709
Abstract
Background: Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), especially in Middle Eastern populations with a high metabolic burden. This study aimed to evaluate the predictive utility of different lipid ratios, including triglyceride-to-high-density [...] Read more.
Background: Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), especially in Middle Eastern populations with a high metabolic burden. This study aimed to evaluate the predictive utility of different lipid ratios, including triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C), total cholesterol (TC)/HDL-C, low-density lipoprotein (LDL-C)/HDL-C, and non-HDL-C/HDL-C, for identifying MetS. In addition, we aimed to characterise the underlying metabolic dysregulation using the most predictive lipid ratio by comparing metabolomic profiles between high-risk (T3) and low-risk (T1) groups. Method: We conducted a cross-sectional study using data from 2179 Qatari adults without CVD and/or T2DM. The predictive value of each lipid ratio for MetS was compared. Untargeted metabolomics was performed to profile metabolic changes between T3 and T1. Results: After adjustment for age, sex, and BMI, TG/HDL-C showed the highest discriminative ability for MetS (AUC = 0.896, 95% CI: 0.88–0.91; OR = 4.36, 95% CI: 3.63–5.28, p < 0.0001). In pairwise AUC comparisons, TG/HDL-C outperformed LDL-C/HDL-C (p = 2.6 × 10−4, after correction for multiple comparisons), with no significant differences versus other ratios. The high-risk group exhibited raised levels of phosphatidylethanolamines, phosphatidylinositols, and diacylglycerols, and lower levels of sphingomyelins and plasmalogens. These lipid classes have been suggested to be implicated in insulin resistance and metabolic dysfunction. Elevated monoacylglycerols were identified in high-TG/HDL-C groups, representing a previously underreported pattern. Conclusions: The TG/HDL-C ratio showed a better association with MetS compared with other lipid ratios and was linked to distinct metabolomic signatures. These findings suggest potential value for early risk evaluation, but longitudinal and mechanistic studies are needed to confirm clinical applicability. Full article
(This article belongs to the Special Issue Current Research in Metabolic Syndrome and Cardiometabolic Disorders)
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Review

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21 pages, 2293 KB  
Review
From Metabolic Syndrome to Atrial Fibrillation: Linking Inflammatory and Fibrotic Biomarkers with Atrial Remodeling and Imaging-Based Evaluation—A Narrative Review
by Adrian-Grigore Merce, Daniel-Dumitru Nisulescu, Anca Hermenean, Oana-Maria Burciu, Iulia-Raluca Munteanu, Adrian-Petru Merce, Daniel-Miron Brie and Cristian Mornos
Metabolites 2026, 16(1), 59; https://doi.org/10.3390/metabo16010059 - 9 Jan 2026
Viewed by 1114
Abstract
Atrial fibrillation (AF) is the most prevalent sustained arrhythmia worldwide and is now increasingly regarded as a disease of chronic inflammation and progressive atrial fibrosis. Understanding of molecular mechanisms that mediate the linkage between systemic metabolic dysregulation, inflammation, and structural atrial changes is [...] Read more.
Atrial fibrillation (AF) is the most prevalent sustained arrhythmia worldwide and is now increasingly regarded as a disease of chronic inflammation and progressive atrial fibrosis. Understanding of molecular mechanisms that mediate the linkage between systemic metabolic dysregulation, inflammation, and structural atrial changes is crucial for informing risk stratification and targeting of prevention strategies. This review provides evidence from 105 studies focusing on the contributions of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), galectin-3, and galectin-1 to cardiac fibrogenesis, atrial fibrosis, and AF pathogenesis. We also link metabolic syndrome to these biomarkers and to atrial remodeling, as well as echocardiographic correlates of fibrosis. TGF-β1 is established as the central profibrotic cytokine and promotes Smad-based fibroblast activation, collagen accumulation, and structural atrial remodeling. Its role is highly potentiated by thrombospondin-1 by turning latent TGF-β1 into its potent form. TNF-α and IL-6 also play an integral role in the inflammatory fibrotic continuum by activating NF-κB and STAT3 signaling, promoting fibroblast proliferation, electrical uncoupling, and extracellular matrix accumulation. Galectin-3 is a potent profibrotic mediator that promotes TGF-β signaling and is a risk factor for negative outcomes, whereas Gal-1 seems to regulate inflammation resolution and may exert context-dependent protective or maladaptive roles. Metabolic syndrome is strongly associated with excessive levels of these biomarkers, chronic low-grade inflammation, oxidative stress, and ventricular and atrial fibrosis. Chronic clinical findings show that metabolic syndrome (MetS) increases AF risk, exacerbates atrial dilatation, and is associated with worse postoperative outcomes. Echocardiographic data are connected to circulating biomarkers and are non-invasive for evaluating atrial remodeling. The evidence to date supports that atrial fibrosis should be considered an end point of systemic inflammation, metabolic dysfunction, and activation of profibrotic molecular pathways. Metabolic syndrome, due to its chronic low-grade inflammatory environment and prolonged levels of metabolic stress, manifests as an important upstream factor of fibrotic remodeling, which continuously promotes the release of cytokines, oxidative stress, and fibroblast activation. Circulating fibrotic biomarkers, in comparison with metabolic syndrome, serve separate yet interdependent pathways that help orchestrate atrial structural remodeling through the simultaneous process but can also provide a long-term indirect measure of ongoing profibrotic activity. The integration of these biomarkers with superior atrial imaging enables a broader understanding of the fibrotic substrate of atrial fibrillation. This combined molecular imaging approach can facilitate risk stratification, refine therapeutic decisions, and facilitate early identification of higher-risk metabolic phenotypes, thus potentially facilitating directed antifibrotic and anti-inflammatory therapy in atrial fibrillation. Full article
(This article belongs to the Special Issue Current Research in Metabolic Syndrome and Cardiometabolic Disorders)
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