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The Impact of Vascular Dysfunction in Obesity and Diabetes

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 April 2025) | Viewed by 3773

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Guest Editor
1. Institute of Physiology, iCBR, Faculty of Medicine, University of Coimbra, 3000-354 Coimbra, Portugal
2. Institute of Physiology, Faculty of Medicine, University of Coimbra, Subunit 1, polo 3, Azinhaga de Santa Comba, Celas, 3000-354 Coimbra, Portugal
Interests: lipid peroxidation; neuroprotective agents; blood glucose; endothelium; vascular
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Special Issue Information

Dear Colleagues,

The impact of vascular dysfunction in obesity and diabetes is a complex and critical problem with far-reaching health implications. Vascular dysfunction, a common and early feature in both conditions, plays a significant role in the development of cardiovascular diseases, which are major causes of morbidity and mortality worldwide. In this special issue we will highlight the mechanisms linking vascular dysfunction to obesity and diabetes and consider the consequences and potential therapeutic strategies. Original articles and reviews are welcome.

Obesity and diabetes are associated with impaired endothelial function, characterized by a reduction in the bioavailability of vasodilators such as nitric oxide (NO). This impairment is often due to oxidative stress, inflammation, and the increased production of vasoconstrictors. In addition, in both obesity and type 2 diabetes, insulin resistance leads to reduced stimulation of endothelial NO synthase, which impairs NO production and endothelial function. In obesity, excess adipose tissue, particularly visceral, secretes pro-inflammatory cytokines (eg. tumor necrosis factor-alpha and interleukin-6) and adipokines that can promote systemic inflammation, contributing to endothelial damage and vascular dysfunction. Both conditions exhibit an increased infiltration of immune cells into vascular walls, further exacerbating inflammation and endothelial injury. Chronic high blood glucose levels in diabetes contribute to the formation of advanced glycation end-products, which can alter the structure and function of vascular tissues, promoting stiffness and reducing elasticity.

The impact on vascular function is significant. Damaged endothelial cells and inflammation lead to the development of atherosclerosis, characterized by plaque formation within arteries, increasing the risk of coronary artery disease and stroke. Impaired vascular function can result in increased peripheral resistance, a hallmark of hypertension, which is commonly observed in individuals with obesity and diabetes. In diabetes, the microvascular complications include retinopathy, nephropathy, and neuropathy, which arise from damage to the small blood vessels supplying the eyes, kidneys, and nerves, respectively. In addition, both obesity and diabetes are risk factors for heart failure, often independent of coronary artery disease, potentially through mechanisms involving myocardial steatosis, lipotoxicity, and diabetic cardiomyopathy.

Understanding and managing vascular dysfunction in obesity and diabetes is crucial for reducing the burden of associated cardiovascular diseases. Continuous research and innovative treatments are imperative to improve outcomes for affected populations globally. Lifestyle modifications (diet, exercise, and weight loss are foundational in managing obesity and diabetes), therapeutic interventions (antidiabetic drugs like agonist of glucagon-like peptide-1, sodium-glucose cotransporter 2 inhibitors not only control blood glucose levels but also show benefits in reducing cardiovascular risks; antihypertensives: angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists are particularly effective in patients with diabetes, as they protect against kidney damage while controlling blood pressure; statins) or surgical interventions can lead to improvements in vascular function.

We need tailoring treatments based on genetic, metabolic, and environmental factors that could enhance efficacy and minimize side effects. Research into new drugs that directly target pathways specific to vascular dysfunction in obesity and diabetes holds promise. Finally, greater focus on preventive measures, including early lifestyle interventions, could mitigate the onset of vascular complications associated with obesity and diabetes.

Dr. Cristina M. Sena
Guest Editor

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Keywords

  • vascular dysfunction
  • insulin resistance
  • inflammation
  • adipokines and cytokines
  • microvascular complications
  • pharmacological treatments
  • surgical interventions
  • cardiovascular diseases
  • personalized medicine
  • novel therapeutics
  • prevention strategies

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Published Papers (3 papers)

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20 pages, 4133 KiB  
Article
Flexible Parametric Survival Modeling of Transaminases as Predictive Biomarkers for Non-Alcoholic Fatty Liver Disease: A Retrospective Longitudinal Study (2012–2022)
by Amr Sayed Ghanem, Ágnes Tóth, Péter Takács, Battamir Ulambayar, Marianna Móré and Attila Csaba Nagy
Int. J. Mol. Sci. 2025, 26(11), 5057; https://doi.org/10.3390/ijms26115057 - 24 May 2025
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common metabolic liver disease linked to obesity and diabetes. This study aimed to assess whether serum GOT and GPT can predict NAFLD early in at-risk individuals. A retrospective cohort study was conducted using hospital records from [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is a common metabolic liver disease linked to obesity and diabetes. This study aimed to assess whether serum GOT and GPT can predict NAFLD early in at-risk individuals. A retrospective cohort study was conducted using hospital records from the University of Debrecen (2012–2022), including 4886 NAFLD-free individuals at baseline. NAFLD incidence was tracked using ICD-10 codes, with transaminase levels (GOT and GPT) and key metabolic comorbidities analyzed as predictors in a longitudinal design. Survival analysis included Fleming–Harrington tests, Kaplan–Meier, and Nelson–Aalen estimators as well as restricted mean survival time. The Royston–Parmar flexible parametric model was used to assess the time-dependent effects of GOT, GPT, and metabolic risk factors on NAFLD incidence. An elevated GOT was significantly associated with an increased NAFLD hazard (HR = 2.71, 95% CI: 1.31–5.58), as was an elevated GPT (HR = 2.21, 95% CI: 1.09–4.43). Disorders of lipid metabolism showed the strongest association (HR = 3.29, 95% CI: 1.51–7.25). Elevated GOT and GPT levels, in combination with demographic and clinical factors, may serve as valuable prognostic biomarkers for NAFLD progression, underscoring the importance of routine liver enzyme monitoring and comprehensive metabolic management to improve long-term patient outcomes. Full article
(This article belongs to the Special Issue The Impact of Vascular Dysfunction in Obesity and Diabetes)
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12 pages, 565 KiB  
Article
The Predictive Role of Inflammatory Biomarkers and Their Correlation with the Biochemical Profile in Patients with Vasculopathy Undergoing Surgery
by Orsolya-Zsuzsa Akácsos-Szász, Sándor Pál, Kinga-Ilona Nyulas, Mónika Szilveszter, Zsuzsánna Simon-Szabó, Lóránd Dénes, Erzsébet Májai, Adina Huțanu, Adina Stoian, Mariana Cornelia Tilinca and Enikő Nemes-Nagy
Int. J. Mol. Sci. 2024, 25(22), 11989; https://doi.org/10.3390/ijms252211989 - 8 Nov 2024
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Abstract
Inflammation is involved in the pathomechanism of vascular diseases. Pro-inflammatory cytokines are important in perioperative monitoring. The aim of the study was the perioperative assessment of biochemical tests and inflammatory markers in patients with vasculopathy, focusing on the identification of subjects prone to [...] Read more.
Inflammation is involved in the pathomechanism of vascular diseases. Pro-inflammatory cytokines are important in perioperative monitoring. The aim of the study was the perioperative assessment of biochemical tests and inflammatory markers in patients with vasculopathy, focusing on the identification of subjects prone to complications. The study was performed between 2020 and 2023 at the Clinical County Hospital in Târgu Mureș on enrolled diabetic and non-diabetic patients with vasculopathy and lower limb surgery (amputation or necrectomy). Pre- and postoperative inflammatory markers, biochemical, and hematological tests (n = 62) were performed. Positive correlation was found between preoperative C-reactive protein (CRP) and interleukin-6 (IL-6) levels, and between preoperative triglyceridemia and glycemia/cholesterolemia. Positive correlation was present between pre- and postoperative values of IL-6, tumor necrosis factor-alfa (TNF-α), CRP, and fibrinogen. Preoperative TNF-α values positively correlated with malondialdehyde (MDA) levels, postoperative TNF-α values with transaminase enzymes. Diabetic patients presented higher IL-6 results compared to non-diabetic subjects. We can conclude that dynamic assessment of inflammatory markers is appropriate for monitoring perioperative course. Half of the subjects presented moderately increased preoperative IL-6 levels, and one quarter had critically high values, which might predict prolonged hospitalization. The assessment of oxidative stress, inflammatory markers and biochemical parameters enables the identification of patients prone to complications, so they can benefit from more complex management. Full article
(This article belongs to the Special Issue The Impact of Vascular Dysfunction in Obesity and Diabetes)
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17 pages, 1754 KiB  
Article
Sexual Dimorphism in Impairment of Acetylcholine-Mediated Vasorelaxation in Zucker Diabetic Fatty (ZDF) Rat Aorta: A Monogenic Model of Obesity-Induced Type 2 Diabetes
by Rifat Ara Islam, Xiaoyuan Han, Sonali Shaligram, Mitra Esfandiarei, John N. Stallone and Roshanak Rahimian
Int. J. Mol. Sci. 2024, 25(20), 11328; https://doi.org/10.3390/ijms252011328 - 21 Oct 2024
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Abstract
Several reports, including our previous studies, indicate that hyperglycemia and diabetes mellitus exert differential effects on vascular function in males and females. This study examines sex differences in the vascular effects of type 2 diabetes (T2D) in an established monogenic model of obesity-induced [...] Read more.
Several reports, including our previous studies, indicate that hyperglycemia and diabetes mellitus exert differential effects on vascular function in males and females. This study examines sex differences in the vascular effects of type 2 diabetes (T2D) in an established monogenic model of obesity-induced T2D, Zucker Diabetic Fatty (ZDF) rats. Acetylcholine (ACh) responses were assessed in phenylephrine pre-contracted rings before and after apocynin, a NADPH oxidase (NOX) inhibitor. The mRNA expressions of aortic endothelial NOS (eNOS), and key NOX isoforms were also measured. We demonstrated the following: (1) diabetes had contrasting effects on aortic vasorelaxation in ZDF rats, impairing relaxation to ACh in females while enhancing it in male ZDF rats; (2) inhibition of NOX, a major source of superoxide in vasculature, restored aortic vasorelaxation in female ZDF rats; and (3) eNOS and NOX4 mRNA expressions were elevated in female (but not male) ZDF rat aortas compared to their respective leans. This study highlights sexual dimorphism in ACh-mediated vasorelaxation in the aorta of ZDF rats, suggesting that superoxide may play a role in the impaired vasorelaxation observed in female ZDF rats. Full article
(This article belongs to the Special Issue The Impact of Vascular Dysfunction in Obesity and Diabetes)
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