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Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and...
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Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and Cardiovascular Pathologies—Second Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 4830

Special Issue Editors

Dr. Cristina Tudoran

E-Mail Website
Guest Editor
1. Department VII, Internal Medicine II, Discipline of Cardiology, University of Medicine and Pharmacy “Victor Babes” Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
2. Centre of Molecular Research in Nephrology and Vascular Disease, University of Medicine and Pharmacy “Vic-tor Babes” Timisoara, E. Murgu Square, Nr. 2, 300041 Timisoara, Romania
3. County Emergency Hospital “Pius Brinzeu”, L. Rebreanu, Nr. 156, 300723 Timisoara, Romania
Interests: pulmonary hypertension; heart failure; heart rate variability; myocarditis; pericarditis; COVID-19 and post-acute COVID-19 syndrome
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Dragos Cozma

E-Mail Website
Guest Editor
1. Department of Cardiology, “Victor Babes” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania
2. Research Center of the Institute of Cardiovascular Diseases Timisoara, 13A Gheorghe Adam Street, 300310 Timisoara, Romania
Interests: echocardiography; left-atrial function; device implantation; complex arrhythmia ablation; heart failure
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Although the association between diabetes mellitus and other metabolic dysfunctions, such as metabolic syndrome and obesity, and cardiovascular pathologies are well known and widely studied, physicians and researchers should not underestimate the enormous impact of other endocrine dysfunctions, commencing with thyroid disorders and other endocrine diseases, on the cardiovascular risk profile of a patient. New developments in genetics, pathophysiology, medical equipment, bioengineering, pharmacology and statistics open new horizons for the diagnosis and management of patients with various metabolic and endocrine dysfunctions, for example, allowing for precocious detection even in a subclinical status of cardiovascular alterations, thus preventing their evolution to a symptomatic disease with multiple consequences for the patient.

The development of new diagnostic/therapeutic methods and protocols is needed to facilitate the precocious diagnosis and assessment of the risk profile, pre-existing cardiovascular pathologies and short- and long-term outcomes in diabetic patients as well as in those with other metabolic and endocrine dysfunctions.

This Special Issue focuses on original articles and reviews referring to groundbreaking research regarding the association between diabetes mellitus and/or other endocrine and metabolic dysfunctions and cardiovascular pathologies.

Dr. Cristina Tudoran
Dr. Dragos Cozma
Guest Editors

Manuscript Submission Information

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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. Biomedicines 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 2600 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

  • diabetes mellitus
  • insulin resistance
  • metabolic syndrome
  • obesity
  • thyroid dysfunction
  • hormonal alterations
  • endothelial dysfunction
  • coronary artery disease
  • hypertension
  • peripheric arterial disease

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Published Papers (7 papers)

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Research

Jump to: Review

15 pages, 1095 KB  
Article
Theophylline Attenuates the Release of Cardiovascular Disease-Related Triglyceride and Cholesterol by Inhibiting the Activity of Microsomal Triglyceride Transfer Protein in Rat Hepatocytes
by Min-Kyu Park, Hyeonha Jang, Jeong-Soo Bae, Jae-Ho Shin and Hwa-Jin Park
Biomedicines 2025, 13(11), 2579; https://doi.org/10.3390/biomedicines13112579 - 22 Oct 2025
Viewed by 162
Abstract
Background/Objectives: Cardiovascular diseases (CVD) remain the leading cause of diet-related mortality, with hepatic overproduction of very-low-density lipoprotein (VLDL) being a central driver of dyslipidemia. The microsomal triglyceride transfer protein (MTP) is essential for this process, and its activity is negatively regulated by [...] Read more.
Background/Objectives: Cardiovascular diseases (CVD) remain the leading cause of diet-related mortality, with hepatic overproduction of very-low-density lipoprotein (VLDL) being a central driver of dyslipidemia. The microsomal triglyceride transfer protein (MTP) is essential for this process, and its activity is negatively regulated by cyclic adenosine monophosphate (cAMP). Theophylline, a methylxanthine found in tea, increases intracellular cAMP. This study aimed to evaluate whether physiologically relevant concentrations of theophylline could beneficially modulate lipoprotein secretion in an ex vivo model of diet-induced MTP activation. Methods: Primary hepatocytes were isolated from rats fed a high-fat, high-carbohydrate diet (HFCD). Cells were treated with 100 µM theophylline, and the secretion of triglyceride (TG), total cholesterol (TC), VLDL-cholesterol (VLDL-C), and HDL-cholesterol (HDL-C) was quantified. Hepatocellular MTP activity and atherogenic indices were also assessed. Results: Compared to untreated control cells, theophylline treatment significantly reduced the secretion of TG by 6% and TC by 24%. Specifically, VLDL-C secretion decreased by 6%, while HDL-C secretion increased substantially by 93%. These lipid-modulating effects were correlated with a 6.9% reduction in MTP activity. Consequently, significant improvements were observed in the atherogenic indices TG/HDL-C, TC/HDL-C, and the atherogenic index (AI) (p < 0.01). Conclusions: Our findings demonstrate that physiologically attainable concentrations of theophylline rebalance lipoprotein secretion by suppressing hepatic MTP activity, shifting the lipid profile toward an anti-atherogenic state. These results highlight the potential of theophylline as a functional dietary component for mitigating diet-induced dyslipidemia and reducing cardiovascular risk. Full article
(This article belongs to the Special Issue Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and Cardiovascular Pathologies—Second Edition)
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24 pages, 920 KB  
Article
Intersecting Endocrine Pathways in Cardiomyopathy: The Role of Metabolic Burden in Structural Heart Disease
by Ovidiu Țica, Mircea Ioan Șandor, Anca Huniadi, Cristian Daina, Sanda Monica Filip, Ilarie Brihan, Monica Sabău, Ioana Zaha and Otilia Țica
Biomedicines 2025, 13(10), 2364; https://doi.org/10.3390/biomedicines13102364 - 26 Sep 2025
Cited by 1 | Viewed by 324
Abstract
Background: Dilated cardiomyopathy (DCM) is a major contributor to heart failure-related morbidity and mortality. While type 2 diabetes mellitus (T2DM), obesity, and thyroid dysfunction are individually linked to cardiovascular disease, their combined effects on DCM remain poorly understood. Objective: To evaluate the independent [...] Read more.
Background: Dilated cardiomyopathy (DCM) is a major contributor to heart failure-related morbidity and mortality. While type 2 diabetes mellitus (T2DM), obesity, and thyroid dysfunction are individually linked to cardiovascular disease, their combined effects on DCM remain poorly understood. Objective: To evaluate the independent and synergistic associations of diabetes (stratified by treatment), thyroid dysfunction, and obesity with the prevalence of DCM and 30-day hospital readmission. We further examined the utility of a composite Metabolic Burden Score for risk stratification. Methods: In this retrospective cohort study, electronic health record data from 1079 adult patients at a tertiary care center were analyzed. Multivariable logistic regression, including ridge regularization, was used to identify predictors of DCM. Endocrine phenotypes were stratified by diabetes and thyroid status. A Metabolic Burden Score (range: 0–3) based on diabetes, obesity, and thyroid dysfunction was developed and correlated with clinical outcomes. Results: DCM was diagnosed in 46% of the cohort. Non-insulin-treated diabetes (OR: 6.93; 95% CI: 3.78–12.73), hypothyroidism (OR: 1.78; 95% CI: 1.02–3.11), and male sex (OR: 2.33; 95% CI: 1.36–4.00) were independently associated with increased DCM risk. Obesity was not independently predictive but contributed to DCM prevalence when assessed within the Metabolic Burden Score. DCM prevalence increased across burden strata, reaching 50% in the high-risk group. Notably, the moderate-risk group had the highest 30-day readmission rate (42.8%). Conclusions: Non-insulin-treated diabetes and hypothyroidism are key metabolic drivers of DCM. A simple composite burden score offers a clinically useful tool for stratifying risk of DCM and early readmission. These findings support integrated endocrine–cardiac screening strategies to improve early identification and prevention of structural heart disease. Full article
(This article belongs to the Special Issue Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and Cardiovascular Pathologies—Second Edition)
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16 pages, 404 KB  
Article
Sex Differences in MASLD After Age 50: Presentation, Diagnosis, and Clinical Implications
by Ilaria Milani, Maria Eugenia Parrotta, Luca Colangeli, Marianna Chinucci, Simonetta Palleschi, Barbara Rossi, Paolo Sbraccia, Alessandro Mantovani, Frida Leonetti, Valeria Guglielmi and Danila Capoccia
Biomedicines 2025, 13(9), 2292; https://doi.org/10.3390/biomedicines13092292 - 18 Sep 2025
Viewed by 1058
Abstract
Background: Age over 50, menopause, obesity and type 2 diabetes (T2D) are key risk factors for Metabolic dysfunction-associated steatotic liver disease (MASLD). This observational study aimed to assess sex differences in anthropometric and clinical profile, including non-invasive liver steatosis indices, in subjects [...] Read more.
Background: Age over 50, menopause, obesity and type 2 diabetes (T2D) are key risk factors for Metabolic dysfunction-associated steatotic liver disease (MASLD). This observational study aimed to assess sex differences in anthropometric and clinical profile, including non-invasive liver steatosis indices, in subjects with MASLD, obesity and/or T2D, aged ≥ 50 years. Methods: Anthropometric and clinical parameters, non-invasive indices for steatosis and fibrosis and FibroScan® data were collected. Results: Among 213 patients (65.7% women, median age 63.0 years and mean Body Mass Index (BMI 34.9 kg/m2), men had higher body weight and waist circumference (WC), whereas women showed higher BMI and waist-to-height ratio (WHtR), and were more likely to exceed WC sex-specific and WHtR risk cut-offs. While transaminases values were higher in men, sex-specific cut-offs revealed that women more frequently exceeded these thresholds. No sex-differences were found for Fatty Liver Index (FLI), Fibrosis-4 (FIB-4) or FibroScan®, although higher rate of mild fibrosis in women. The diagnostic accuracy of FLI for detecting steatosis was significantly higher in men and unsatisfactory in women (Area Under the ROC Curve, AUC 0.863 vs. 0.655). Conclusions: While MASLD is more common in men, these results suggest that postmenopausal women with visceral obesity showed similar or worse liver and cardiometabolic profiles than men, despite appearing healthier based on standard clinical parameters. Notably, common markers like transaminases and the FLI were less accurate in detecting steatosis in women, underscoring the need for sex-specific diagnostic criteria and greater clinical attention to older women, particularly those with central obesity, to ensure early identification and management of MASLD. Full article
(This article belongs to the Special Issue Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and Cardiovascular Pathologies—Second Edition)
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Review

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16 pages, 447 KB  
Review
Tertiary Hyperparathyroidism in Diabetic Nephropathy: An Underrecognized Complication—A Narrative Review
by Mirona Costea, Dana-Mihaela Tilici, Diana Loreta Paun, Vanda Roxana Nimigean, Sorin Constantin Paun and Rucsandra Elena Danciulescu-Miulescu
Biomedicines 2025, 13(11), 2604; https://doi.org/10.3390/biomedicines13112604 - 24 Oct 2025
Viewed by 169
Abstract
Tertiary hyperparathyroidism (THPT) arises in patients with chronic kidney disease (CKD) as a consequence of prolonged secondary hyperparathyroidism and is marked by autonomous parathyroid hormone (PTH) secretion. In some cases, parathyroid hyperplasia persists even after successful renal transplantation, resulting in sustained PTH elevation [...] Read more.
Tertiary hyperparathyroidism (THPT) arises in patients with chronic kidney disease (CKD) as a consequence of prolonged secondary hyperparathyroidism and is marked by autonomous parathyroid hormone (PTH) secretion. In some cases, parathyroid hyperplasia persists even after successful renal transplantation, resulting in sustained PTH elevation and hypercalcaemia. These alterations contribute to bone loss, vascular calcification, and increased cardiovascular risk. Management includes medical therapy with calcimimetics or vitamin D analogues and surgical intervention via parathyroidectomy. However, optimal timing and treatment strategy remain uncertain. This review examines the pathophysiology, clinical manifestations, and current management paradigms of THPT, with an emphasis on areas that require further research and consensus. Full article
(This article belongs to the Special Issue Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and Cardiovascular Pathologies—Second Edition)
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17 pages, 695 KB  
Review
Statins, Vitamin D, and Cardiovascular Health: A Comprehensive Review
by Dragos Cozma, Cristina Tudoran and Cristina Văcărescu
Biomedicines 2025, 13(10), 2515; https://doi.org/10.3390/biomedicines13102515 - 15 Oct 2025
Viewed by 599
Abstract
Statins are widely used lipid-lowering agents that significantly reduce cardiovascular morbidity and mortality by lowering LDL-cholesterol. Vitamin D, traditionally known for its skeletal role, is increasingly recognized for its cardiovascular relevance. This study aims to focus on the complex relationship between statins, vitamin [...] Read more.
Statins are widely used lipid-lowering agents that significantly reduce cardiovascular morbidity and mortality by lowering LDL-cholesterol. Vitamin D, traditionally known for its skeletal role, is increasingly recognized for its cardiovascular relevance. This study aims to focus on the complex relationship between statins, vitamin D, and their impact on cardiovascular outcomes. Both molecules intersect metabolically at 7-dehydrocholesterol, raising interest in their potential interactions. While theoretical concerns exist about statins impairing vitamin D synthesis, clinical studies suggest a neutral or modestly positive effect on circulating 25(OH)D levels. Statins may increase vitamin D levels by inhibiting its catabolism (via CYP3A4) and enhancing absorption. Observational data also suggest synergy between statins and vitamin D in reducing inflammation, oxidative stress, endothelial dysfunction, and atherogenesis. Though large trials showed no benefit of vitamin D supplementation in cardiovascular event reduction among vitamin D–replete individuals, select subgroups (those deficient or with statin-induced myalgia) may benefit from targeted supplementation. Optimizing vitamin D status could improve statin tolerability and adherence, especially in high-risk populations such as the elderly or those with metabolic syndrome. This review highlights the complex interplay between statins and vitamin D and supports a personalized approach to supplementation in statin-treated patients, aiming to enhance cardiovascular protection without overtreatment. Full article
(This article belongs to the Special Issue Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and Cardiovascular Pathologies—Second Edition)
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25 pages, 1204 KB  
Review
A Clinical Review of the Connections Between Diabetes Mellitus, Periodontal Disease, and Cardiovascular Pathologies
by Otilia Țica, Ioana Romanul, Gabriela Ciavoi, Vlad Alin Pantea, Ioana Scrobota, Lucian Șipoș, Cristian Marius Daina and Ovidiu Țica
Biomedicines 2025, 13(9), 2309; https://doi.org/10.3390/biomedicines13092309 - 20 Sep 2025
Cited by 1 | Viewed by 1131
Abstract
Background: Diabetes mellitus (DM), periodontal disease (PD), and cardiovascular disease (CVD) are highly prevalent global health conditions with overlapping pathophysiological mechanisms. Emerging evidence suggests a bidirectional and synergistic relationship among them, driven by chronic inflammation, immune dysregulation, oxidative stress, and microbial dysbiosis. [...] Read more.
Background: Diabetes mellitus (DM), periodontal disease (PD), and cardiovascular disease (CVD) are highly prevalent global health conditions with overlapping pathophysiological mechanisms. Emerging evidence suggests a bidirectional and synergistic relationship among them, driven by chronic inflammation, immune dysregulation, oxidative stress, and microbial dysbiosis. Objective: This review synthesizes current literature on the interconnectedness of DM, PD, and CVD, emphasizing shared molecular pathways, clinical implications, and opportunities for integrated management. Methods: A systematic review and narrative synthesis of recent clinical trials, observational studies, and multi-omics investigations was conducted to explore the mechanisms linking these three conditions. A structured literature search was performed across PubMed, Scopus, and Web of Science from database inception until 30 June 2025. Key findings were contextualized within systems biology, precision medicine, and real-world clinical strategies. Results: DM exacerbates periodontal inflammation and accelerates tissue destruction via hyperglycemia-induced inflammatory mediators, while periodontitis worsens glycemic control and insulin resistance. Both conditions independently elevate cardiovascular risk, and their co-occurrence significantly amplifies the incidence of adverse cardiovascular events. Shared biomarkers such as Interleukin (IL)-6, Tumor Necrosis Factor (TNF)-α, and CRP, as well as overlapping genetic and epigenetic signatures, underscore a common inflammatory axis. Periodontal therapy has demonstrated modest but meaningful benefits on glycemic control and endothelial function, while cardiometabolic therapies (e.g., statins, Glucagon-Like Peptide (GLP-1) receptor agonists, SGLT2 inhibitors) show potential to improve periodontal outcomes. Probiotics, microbiome-targeted therapies, and AI-based risk models are emerging as future tools. Conclusions: DM, PD, and CVD form a mutually reinforcing triad mediated by systemic inflammation and metabolic dysregulation. Integrated, multidisciplinary care models and precision health strategies are essential to address this inflammatory burden and improve long-term outcomes. Further large-scale interventional trials and mechanistic human studies are needed to establish causal links and optimize combined therapeutic approaches. Full article
(This article belongs to the Special Issue Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and Cardiovascular Pathologies—Second Edition)
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32 pages, 1259 KB  
Review
Cardiac Endocrine Function and Hormonal Interplay in Pediatrics: From Development to Clinical Implications
by Valeria Calcaterra, Savina Mannarino, Filippo Puricelli, Giulia Fini, Giulia Cecconi, Martina Evangelista, Beatrice Baj, Cassandra Gazzola and Gianvincenzo Zuccotti
Biomedicines 2025, 13(9), 2225; https://doi.org/10.3390/biomedicines13092225 - 10 Sep 2025
Viewed by 809
Abstract
The endocrine system plays a pivotal role in all stages of cardiac development and in maintaining the structural and functional integrity of the heart. Notably, the heart itself functions as an endocrine organ, producing hormones that regulate blood pressure, fluid balance, and myocardial [...] Read more.
The endocrine system plays a pivotal role in all stages of cardiac development and in maintaining the structural and functional integrity of the heart. Notably, the heart itself functions as an endocrine organ, producing hormones that regulate blood pressure, fluid balance, and myocardial remodeling. This narrative review explores the endocrine mechanisms underlying cardiac development and function, with a focus on fetal and pediatric life. Special attention is given to the heart’s intrinsic endocrine activity and how hormonal signals interact with the cardiovascular system during early development. Hormonal signaling is essential for maintaining physiological homeostasis and supporting proper heart development during growth. Disruptions in these signals may serve as silent precursors to structural or functional heart disease, potentially manifesting later in life. Understanding these interactions is clinically relevant, as endocrine imbalances can contribute to the onset, progression, and prognosis of pediatric cardiac disorders. Early identification of hormonal dysregulation can help prevent or mitigate adverse cardiovascular outcomes. Furthermore, recognizing age-specific patterns in hormone–heart interactions may enable the development of targeted diagnostic and therapeutic strategies. Full article
(This article belongs to the Special Issue Connections Between Diabetes Mellitus, Other Metabolic and Endocrine Dysfunctions and Cardiovascular Pathologies—Second Edition)
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