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Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus

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

Deadline for manuscript submissions: closed (31 May 2025) | Viewed by 12768

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Dr. Maciej Walędziak

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Department of General, Oncological, Metabolic and Thoracic Surgery, Military Institute of Medicine—National Research Institute, Szaserów 128 St., 04-141 Warsaw, Poland
Interests: metabolic disorders; obesity; type 2 diabetes mellitus; bariatric surgery
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Anna Maria Różańska-Walędziak

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Department of Human Physiology and Patophysiology, Faculty of Medicine, Collegium Medicum, Cardinal Stefan Wyszynski, 01-938 Warsaw, Poland
Interests: nutrition and supplementation after bariatric surgery; pregnancy after bariatric surgery; laparoscopic sleeve gastrectomy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic disorders, obesity, and type 2 diabetes mellitus have become global health problems in recent decades. The prevalence of obesity increases every year, and it is associated with a higher risk of developing co-morbidities, including cardiovascular disease, metabolic dysfunction, and type 2 diabetes mellitus, therefore becoming equivalent to metabolic syndrome. Adipose tissue cells release various mediators such as adipokines, cytokines, and chemokines, leading to chronic inflammatory process. Hyperglycemia, insulin tissue resistance, or abnormal lipid profiles are only some examples of metabolic changes in patients with obesity.

This Special Issue will include original research and in-depth reviews with the most recent insights into topics related to the molecular and biochemical mechanisms of metabolic changes in obesity; changes in laboratory parameters in patients with obesity and other metabolic disorders; and new preventive/therapeutic strategies for treating obesity and its co-morbidities.

Dr. Maciej Walędziak
Prof. Dr. Anna Maria Różańska-Walędziak
Guest Editors

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Keywords

metabolic disorders
obesity
type 2 diabetes mellitus
bariatric surgery
laboratory parameters

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Related Special Issue

Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus—2nd Edition in Biomedicines

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Research

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23 pages, 6722 KiB

Open AccessArticle

Identification of Glycolysis-Related Genes in MAFLD and Their Immune Infiltration Implications: A Multi-Omics Analysis with Experimental Validation

by Jiawei Chen, Siqi Yang, Diwen Shou, Bo Liu, Shaohan Li, Tongtong Luo, Huiting Chen, Chen Huang and Yongjian Zhou

Biomedicines 2025, 13(7), 1636; https://doi.org/10.3390/biomedicines13071636 - 3 Jul 2025

Viewed by 365

Abstract

Background: Metabolic-associated fatty liver disease (MAFLD) is characterized by metabolic syndrome and immune infiltration, with glycolysis pathway activation emerging as a pivotal contributor. This study aims to identify glycolysis-associated key genes driving MAFLD progression and elucidate their crosstalk with immune infiltration through bioinformatics analysis and experimental validation. Methods: Integrative multi-omics analysis was performed on bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets from MAFLD patients and controls. Differential expression analysis and WGCNA were employed to pinpoint glycolysis-correlated key genes. The relationship with immune infiltration was analyzed using single-cell and spatial transcriptomics technologies. Machine learning was applied to identify feature genes for matching shared TFs and miRNAs. External cohort validation and in vivo experiments (methionine choline-deficient diet murine models) were conducted for biological confirmation. Results: Five glycolysis-associated key genes (ALDH3A1, CDK1, DEPDC1, HKDC1, SOX9) were identified and validated as MAFLD discriminators. Single-cell analysis revealed that the hepatocyte–fibroblast–macrophage axis constitutes the predominant glycolysis-active niche. Spatial transcriptomics showed that CDK1, SOX9, and HKDC1 were colocalized with the monocyte-derived macrophage marker CCR2. Using four machine learning models, four feature genes were identified, along with their common transcription factors YY1 and FOXC1, and the miRNA “hsa-miR-590-3p”. External datasets and experimental validation confirmed that the key genes were upregulated in MAFLD samples. Conclusions: In this study, we identified five glycolysis-related key genes in MAFLD and explored their relationship with immune infiltration, providing new insights for diagnosis and metabolism-directed immunomodulation strategies in MAFLD. Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus)

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13 pages, 640 KiB

Open AccessArticle

Investigating the Role of GDF-15 in Diabetes and Obesity: A Comprehensive Analysis of a Cohort from the KDEP Study

by Jehad Abubaker, Mohamed Abu-Farha, Ahmed N. Albatineh, Irina Al-Khairi, Preethi Cherian, Hamad Ali, Ibrahim Taher, Fahad Alajmi, Mohammed Qaddoumi, Muhammad Abdul-Ghani and Fahd Al-Mulla

Biomedicines 2025, 13(7), 1589; https://doi.org/10.3390/biomedicines13071589 - 30 Jun 2025

Viewed by 343

Abstract

Background: Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-β (TGF-β) superfamily, is upregulated under cellular stress conditions and has emerged as a potential biomarker for metabolic disorders. However, its expression in relation to diabetes and obesity across different demographic groups remains understudied. This study investigated the association between plasma GDF-15 levels, diabetes mellitus, and obesity in individuals of varying ages, ethnicities, and genders. Methods: In a cross-sectional study, plasma GDF-15 concentrations were measured in 2083 participants enrolled in the Kuwait Diabetes Epidemiology Program (KDEP). The dataset included anthropometric, clinical, biochemical, and glycemic markers. Multivariate regression analysis was used to examine associations between GDF-15 levels and metabolic phenotypes. Results: Mean plasma GDF-15 levels were significantly higher in males than females (580.6 vs. 519.3 ng/L, p < 0.001), and in participants >50 years compared to those <50 years (781.4 vs. 563.4 ng/L, p < 0.001). Arab participants had higher GDF-15 levels than South and Southeast Asians (597.0 vs. 514.9 and 509.9 ng/L, respectively; p < 0.001). Positive correlations were found with BMI, waist and hip circumferences, blood pressure, insulin, and triglycerides; negative correlations were observed with HDL cholesterol. Median regression indicated that elevated GDF-15 levels were independently and significantly associated with male gender, older age, obesity, diabetes, and insulin resistance. Adjusted median regression indicated that male gender (β = 30.1, 95%CI: 11.7, 48.5), older age (β = 9.4, 95%CI: 8.0, 10.7), and insulin resistance (β = 7.73, 95%CI: 1.47, 14.0) indicated a significant positive association with GDF-15. South Asian participants (β= −41.7, 95%CI: −67.2, −16.2) had significantly but Southeast Asian participants (β= −23.3, 95%CI: −49.2, 2.56) had marginally significantly lower GDF-15 levels compared to participants of Arab ethnicity. Conclusions: Higher GDF-15 levels are associated with age, male gender, Arab ethnicity, obesity, and diabetic traits. These findings support the potential role of GDF-15 as a biomarker for metabolic disorders, particularly in high-risk demographic subgroups. Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus)

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11 pages, 704 KiB

Open AccessArticle

Impaired Glucose Tolerance and Altered Body Composition in Obese Young Adults: A Case–Control Study

by Himan Mohamed-Mohamed, Teresa Pardo-Moreno, Margarita Jimenez-Palomares, Bibiana Perez-Ardanaz, Encarnación M. Sánchez-Lara, Maria D. Vazquez-Lara, Mario de La Mata-Fernandez, Victoria García-Morales and Juan José Ramos-Rodríguez

Biomedicines 2025, 13(7), 1569; https://doi.org/10.3390/biomedicines13071569 - 26 Jun 2025

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Abstract

Background/Objectives: To examine the association between body composition and glucose tolerance in young adults with normal weight, overweight, or obesity. Methods: This observational case–control study included 154 healthy individuals aged 18–25 years. Participants were categorized into three BMI-based groups and underwent anthropometric and body composition assessments using bioelectrical impedance. Glucose tolerance was evaluated via oral glucose tolerance testing, with capillary blood samples collected at baseline and at 30, 60, 90, and 120 min post load. Results: Compared to the normal-weight group, overweight and obese individuals exhibited significantly higher body weight, BMI, visceral and total fat percentages, and reduced muscle mass. Obese participants also showed a significantly greater glucose area under the curve (AUC) and higher fasting and post-load glucose levels. Visceral fat was positively correlated with metabolic impairment. These results indicate a progressive decline in glucose tolerance associated with increasing adiposity and reduced lean mass. Conclusions: Young adults with elevated BMI already demonstrate marked alterations in body composition and impaired glucose tolerance, even in the absence of overt metabolic disease. These findings underscore the importance of the early identification of at-risk individuals using simple, non-invasive tools. Preventive strategies promoting healthy body composition in early adulthood may reduce the future risk of diabetes and its associated complications. Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus)

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15 pages, 283 KiB

Open AccessArticle

The Interactive Effects of Fruit Intake Frequency and Serum miR-484 Levels as Biomarkers for Incident Type 2 Diabetes in a Prospective Cohort of the Spanish Adult Population: The Di@bet.es Study

by Ana Lago-Sampedro, Wasima Oualla-Bachiri, Cristina Maldonado-Araque, Sergio Valdés, Inmaculada González-Molero, Viyey Doulatram-Gamgaram, Elias Delgado, Felipe J. Chaves, Luis Castaño, Alfonso Calle-Pascual, Josep Franch-Nadal, Gemma Rojo-Martínez, Sara García-Serrano and Eva García-Escobar

Biomedicines 2025, 13(1), 160; https://doi.org/10.3390/biomedicines13010160 - 10 Jan 2025

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Background/Objectives: Although evidence suggests that miR-484 and several fruit components are involved in glucose metabolism and insulin resistance metabolic pathways, the relationship between serum miR-484 levels and fruit consumption in relation to the risk of Type 2 diabetes (T2DM) remains elusive. The aim of this study was to evaluate the possible association between serum miR-484 levels and fruit intake frequency with the risk of T2DM in the Spanish adult population. Methods: 2234 subjects from the Di@bet.es cohort study without T2DM at baseline were studied. Socio-demographic, anthropometric and clinical data were recorded, as well as responses to a questionnaire on habits, including frequency of fruit consumption (daily vs. occasional). T2DM was diagnosed at baseline and after 7.5 years of follow-up. Baseline serum miR-484 levels were measured using real-time qPCR and categorized based on the 25th percentile. Association analyses were performed using logistic regression models adjusted for potential confounders. Interaction effects were evaluated on the multiplicative and additive scales. Results: There was no association between miR-484 levels and fruit intake frequency. Categorized miR-484 levels and fruit consumption were inversely and independently associated with the likelihood of incident T2DM. Analysis of the interaction effect suggests the presence of both positive multiplicative and additive interactions between miR-484 categories and fruit consumption frequency. Conclusions: Our study demonstrates a protective effect of daily fruit intake and high miR-484 levels regarding the risk of T2DM and supports the nutritional recommendations advocating daily fruit consumption. This study also suggests that the combined effect of low miR-484 levels and occasional fruit intake may increase the risk of T2DM beyond their independent effects. Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus)

21 pages, 1153 KiB

Open AccessArticle

Reference Interval for Glycated Albumin, 1,5-AG/GA, and GA/HbA1c Ratios and Cut-Off Values for Type 1, Type 2, and Gestational Diabetes: A Cross-Sectional Study

by Yusra Al-Lahham, Waldemar Volanski, Liana Signorini, Ademir Luiz do Prado, Glaucio Valdameri, Vivian Rotuno Moure, Marciane Welter, Alexessander C. Alves, Marcel Henrique Marcondes Sari, Fabiane Gomes de Moraes Rego and Geraldo Picheth

Biomedicines 2024, 12(12), 2651; https://doi.org/10.3390/biomedicines12122651 - 21 Nov 2024

Cited by 1 | Viewed by 1400 | Correction

Abstract

Background/Objectives: Glycated albumin (GA) serves as a biomarker for short-term glycemic control (2–3 weeks), playing a role in diabetes management. Our goal was to establish reference intervals (RIs) for serum GA, and the ratios of 1,5-anhydroglucitol to GA (AGI) and GA to HbA1c in a Euro-Brazilian pediatric population (10 y, n = 299), adults (43.5 y; n = 290), and pregnant women (26 y, n = 406; 26.5 ± 3.1 gestation weeks). Methods: Receiver operating characteristic curve analysis was employed to determine RIs for type 1 diabetes (T1D) in children (n = 148) and adults (n = 81), type 2 diabetes (T2D, n = 283), and gestational diabetes mellitus (GDM, n = 177). Results: Both non-pregnant and pregnant women exhibited GA RIs of 10.0–13.3% and 10.6–14.7%, respectively. The AGI ratio varied from 1.2–4.3 in children, 0.9–3.6 in adults, and 0.8–3.1 in pregnant women. Meanwhile, the GA/HbA1c ratio ranged from 1.8–2.6 in children and adults to 2.3–3.6 in pregnant women. GA and AGI ratios accurately differentiated between T1D and T2D, demonstrating high sensitivity (>84%) and specificity (>97%), with AGI showing superior performance (AUC > 0.99). The GA/HbA1c ratio exhibited moderate discriminatory power (AUC > 0.733) but was less effective in distinguishing adult-onset T1D and T2D, suggesting its limited utility in certain groups. Conclusions: The proposed RIs are consistent with those of other Caucasian populations, affirming their relevance for Euro-Brazilian patients. The GA and AGI ratios emerge as valuable diagnostic tools for T1D and T2D, though their reduced sensitivity in diagnosing GDM warrants further investigation. Clinicians might leverage GA and AGI ratios for more tailored diabetes management, especially when HbA1c results are not optimal. Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus)

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15 pages, 2982 KiB

Open AccessArticle

The Association between the Firmicutes/Bacteroidetes Ratio and Body Mass among European Population with the Highest Proportion of Adults with Obesity: An Observational Follow-Up Study from Croatia

by Andrija Karačić, Ira Renko, Željko Krznarić, Sanja Klobučar and Ana-Marija Liberati Pršo

Biomedicines 2024, 12(10), 2263; https://doi.org/10.3390/biomedicines12102263 - 4 Oct 2024

Cited by 10 | Viewed by 3836

Abstract

Background/Objectives: The phyla Firmicutes and Bacteroidetes are the main constituents of the gut microbiota. An imbalance in the gut microbiota is a sign of dysbiosis, and the Firmicutes-to-Bacteroidetes ratio has been proposed to be a marker of it, especially in the context of obesity. Since Croatia is the country with one of the highest obesity rates in Europe, a pilot observational study was conducted. The aim of the study was to investigate the validity of this potential biomarker in a methodological study using sample processing, DNA sequence analysis and characterization of recruited participants, including various health factors. Methods: A study involving Croatian population was conducted. Participants age, body weight, gender, health history and lifestyle factors were recorded. Gut microbiota composition was analyzed using 16S rRNA sequencing. The F/B ratio was calculated and evaluated in the context of health factors. Statistical analysis was performed to detect the possible association of F/B ratio and excess body weight (kg) and possible impact of certain lifestyle factors. Results: No association between the F/B ratio and excess body weight (kg) was found. Excess body weight was significantly associated with higher age, male gender, and history of appendectomy. No significant health predictors of the F/B ratio were found, but weight gain was positively associated with a higher average F/B ratio. Conclusions: Although this study could not confirm the predictive value of the F/B ratio or any other phyla-related biomarker for excess body weight in the study population, it demonstrated interesting insights into the obesity-associated gut microbiota. Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus)

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Review

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29 pages, 1998 KiB

Open AccessReview

Pentraxin-3 as a Biomarker in Diabetes Mellitus: Insights into Inflammation, Vascular Complications, and Modulation by Antidiabetic Medications

by Roxana-Cristina Dobriceanu, Andreea Daniela Meca, Ianis Kevyn Stefan Boboc, Liliana Mititelu-Tartau, Mihaela Simona Naidin, Adina Turcu-Stiolica and Maria Bogdan

Biomedicines 2025, 13(4), 891; https://doi.org/10.3390/biomedicines13040891 - 7 Apr 2025

Viewed by 821

Abstract

Diabetes mellitus (DM) is a multifactorial metabolic disorder associated with systemic inflammation and vascular complications. Pentraxin-3 (PTX3) has emerged as a key biomarker of inflammation and endothelial dysfunction in DM. We aimed to examine the role of PTX3 in DM and assesses the impact of pharmacological interventions on its expression. The review included studies analyzing PTX3 modulation by antidiabetic therapies, such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 agonists (GLP-1a), and dipeptidyl peptidase-4 inhibitors (DPP-4i), as well as the effects of lifestyle interventions. Clinical and experimental studies demonstrated a strong correlation between PTX3 levels and DM progression. Elevated PTX3 levels were associated with diabetic complications, including nephropathy, retinopathy, and cardiovascular diseases. Antidiabetic drugs showed differential effects on PTX3 expression, with GLP-1a and DPP-4i significantly reducing PTX3 levels, while SGLT-2i displayed a paradoxical increase. Lifestyle interventions, including dietary modifications and weight loss, yielded inconsistent effects, suggesting genetic and metabolic factors influence PTX3 regulation. While pharmacological therapies, particularly GLP-1a and DPP-4i, demonstrate anti-inflammatory effects, further research is needed to standardize PTX3 measurement and explore its potential as a therapeutic target. Personalized treatment strategies incorporating genetic profiling may optimize inflammation control and disease management in DM patients. Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus)

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30 pages, 1571 KiB

Open AccessReview

Omentin—General Overview of Its Role in Obesity, Metabolic Syndrome and Other Diseases; Problem of Current Research State

by Hubert Mateusz Biegański, Krzysztof Maksymilian Dąbrowski and Anna Różańska-Walędziak

Biomedicines 2025, 13(3), 632; https://doi.org/10.3390/biomedicines13030632 - 5 Mar 2025

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Abstract

Background: Omentin (omentin-1, intelectin-1, ITLN-1) is an adipokine considered to be a novel substance. Many chronic, inflammatory, or civilization diseases are linked to obesity, in which omentin plays a significant role. Methods: MEDLINE and SCOPUS databases were searched using the keywords “omentin” or “intelectin-1”. Then the most recent articles providing new perspectives on the matter and the most important studies, which revealed crucial insight, were selected to summarize the current knowledge on the role of omentin in a literature review. Results and Conclusions: The valid role of this adipokine is evident in the course of metabolic syndrome. In most cases, elevated omentin expression is correlated with the better course of diseases, including: type 2 diabetes mellitus, polycystic ovary syndrome, rheumatoid arthritis, metabolic dysfunction-associated steatotic liver disease, Crohn’s disease, ulcerative colitis, atherosclerosis, or ischemic stroke, for some of which it can be a better marker than the currently used ones. However, results of omentin studies are not completely one-sided. It was proven to participate in the development of asthma and atopic dermatitis and to have different concentration dynamics in various types of tumors. All of omentin’s effects and properties make it an attractive subject of research, considering still unexplored inflammation mechanisms, in which it may play an important role. Omentin was proven to prevent osteoarthritis, hepatocirrhosis, and atherosclerosis in mouse models. All of the above places omentin among potential therapeutic products, and not only as a biomarker. However, the main problems with the omentin’s research state are the lack of standardization, which causes many contradictions and disagreements in this field. Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus)

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13 pages, 737 KiB

Open AccessReview

Decoding Health: Exploring Essential Biomarkers Linked to Metabolic Dysfunction-Associated Steatohepatitis and Type 2 Diabetes Mellitus

by Sulagna Mukherjee and Seung-Soon Im

Biomedicines 2025, 13(2), 359; https://doi.org/10.3390/biomedicines13020359 - 4 Feb 2025

Cited by 3 | Viewed by 1725

Abstract

The investigation of biomarkers for metabolic diseases such as type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatohepatitis (MASH) reveals their potential for advancing disease treatment and addressing their notable overlap. The connection between MASH, obesity, and T2DM highlights the need for an integrative management approach addressing mechanisms like insulin resistance and chronic inflammation. Obesity contributes significantly to the development of MASH through lipid dysregulation, insulin resistance, and chronic inflammation. Selective biomarker targeting offers a valuable strategy for detecting these comorbidities. Biomarkers such as CRP, IL-6, and TNF-α serve as indicators of inflammation, while HOMA-IR, fasting insulin, and HbA1c are essential for evaluating insulin resistance. Additionally, triglycerides, LDL, and HDL are crucial for comprehending lipid dysregulation. Despite the growing importance of digital biomarkers, challenges in research methodologies and sample variability persist, necessitating further studies to validate diagnostic tools and improve health interventions. Future opportunities include developing non-invasive biomarker panels, using multiomics, and using machine learning to enhance prognoses for diagnostic accuracy and therapeutic outcomes. Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus)

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