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22 pages, 1641 KiB  
Article
Site-Specific Trafficking of Lipid and Polar Metabolites in Adipose and Muscle Tissue Reveals the Impact of Bariatric Surgery-Induced Weight Loss: A 6-Month Follow-Up Study
by Aidan Joblin-Mills, Zhanxuan E. Wu, Garth J. S. Cooper, Ivana R. Sequeira-Bisson, Jennifer L. Miles-Chan, Anne-Thea McGill, Sally D. Poppitt and Karl Fraser
Metabolites 2025, 15(8), 525; https://doi.org/10.3390/metabo15080525 (registering DOI) - 2 Aug 2025
Abstract
Background: The causation of type 2 diabetes remains under debate, but evidence supports both abdominal lipid and ectopic lipid overspill into tissues including muscle as key. How these depots differentially alter cardiometabolic profile and change during body weight and fat loss is not [...] Read more.
Background: The causation of type 2 diabetes remains under debate, but evidence supports both abdominal lipid and ectopic lipid overspill into tissues including muscle as key. How these depots differentially alter cardiometabolic profile and change during body weight and fat loss is not known. Methods: Women with obesity scheduled to undergo bariatric surgery were assessed at baseline (BL, n = 28) and at 6-month follow-up (6m_FU, n = 26) after weight loss. Fasting plasma (Pla), subcutaneous thigh adipose (STA), subcutaneous abdominal adipose, (SAA), and thigh vastus lateralis muscle (VLM) samples were collected at BL through surgery and at 6m_FU using needle biopsy. An untargeted liquid chromatography mass spectrometry metabolomics platform was used. Pla and tissue-specific lipid and polar metabolite profiles were modelled as changes from BL and 6m_FU. Results: There was significant body weight (−24.5 kg) loss at 6m_FU (p < 0.05). BL vs. 6m_FU tissue metabolomics profiles showed the largest difference in lipid profiles in SAA tissue in response to surgery. Conversely, polar metabolites were more susceptible to change in STA and VLM. In Pla samples, both lipid and polar metabolite profiles showed significant differences between timepoints. Jaccard–Tanimoto coefficient t-tests identified a sub-group of gut microbiome and dietary-derived omega-3-fatty-acid-containing lipid species and core energy metabolism and adipose catabolism-associated polar metabolites that are trafficked between sample types in response to bariatric surgery. Conclusions: In this first report on channelling of lipids and polar metabolites to alternative tissues in bariatric-induced weight loss, adaptive shuttling of small molecules was identified, further promoting adipose processing and highlighting the dynamic and coordinated nature of post-surgical metabolic regulation. Full article
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14 pages, 1040 KiB  
Article
Diabetes Worsens Outcomes After Asphyxial Cardiac Arrest in Rats
by Matthew B. Barajas, Takuro Oyama, Masakazu Shiota, Zhu Li, Maximillian Zaum, Ilija Zecevic and Matthias L. Riess
Diabetology 2025, 6(8), 78; https://doi.org/10.3390/diabetology6080078 (registering DOI) - 1 Aug 2025
Abstract
Background: Diabetes mellitus is associated with worse outcomes after cardiac arrest. Hyperglycemia, diabetes treatments and other long-term sequalae may contribute to this association. We sought to determine the acute effect of diabetes on the return of spontaneous circulation (ROSC) and post-arrest cardiac function [...] Read more.
Background: Diabetes mellitus is associated with worse outcomes after cardiac arrest. Hyperglycemia, diabetes treatments and other long-term sequalae may contribute to this association. We sought to determine the acute effect of diabetes on the return of spontaneous circulation (ROSC) and post-arrest cardiac function in a rat cardiac arrest model. Methods: Eighteen male Wistar rats were utilized, and 12 underwent the induction of type II diabetes for 10 weeks through a high-fat diet and the injection of streptozotocin. The carotid artery flow and femoral arterial pressure were measured. Seven minutes of asphyxial cardiac arrest was induced. An external cardiac compression was performed via an automated piston. Post-ROSC, epinephrine was titrated to a mean arterial pressure (MAP) of 70 mmHg. Data was analyzed using the Mann–Whitney test. The significance was set at p ≤ 0.05. Results: The rate of the ROSC was significantly lower in animals with diabetes, 50% compared to 100% in non-diabetics. Additionally, it took significantly longer to achieve the ROSC in diabetics, p = 0.034. In animals who survived, the cardiac function was reduced, as indicated by an increased epinephrine requirement, p = 0.041, and a decreased cardiac output at the end of the experiment, p = 0.017. The lactate, venous and arterial pressures, heart rate and carotid flow did not differ between groups at 2 h. Conclusions: Diabetes negatively affects the survival from cardiac arrest. Here, the critical difference was the rate of the conversion to a life-sustaining rhythm and the achievement of the ROSC. The post-ROSC cardiac function was depressed in diabetic animals. Interventions targeted at improving defibrillation success may be important in diabetics. Full article
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14 pages, 251 KiB  
Article
Self-Reported Physical Activity Among Individuals with Diabetes Mellitus in Germany—Identifying Potential Barriers and Facilitators
by Frederike Maria Meuffels, Celine Lichtmess, Thorsten Kreutz, Steffen Held and Christian Brinkmann
Diabetology 2025, 6(8), 77; https://doi.org/10.3390/diabetology6080077 (registering DOI) - 1 Aug 2025
Abstract
Background/Objectives: Physical activity is a cornerstone of diabetes mellitus (DM) management and is strongly recommended in the American Diabetes Association (ADA)’s guidelines. This study aims to investigate the self-reported physical activity levels of individuals with DM in Germany, as well as the barriers [...] Read more.
Background/Objectives: Physical activity is a cornerstone of diabetes mellitus (DM) management and is strongly recommended in the American Diabetes Association (ADA)’s guidelines. This study aims to investigate the self-reported physical activity levels of individuals with DM in Germany, as well as the barriers and facilitators they encounter. Methods: Individuals with type 1 DM (T1DM) and type 2 DM (T2DM) were asked to fill out an online questionnaire that was partly based on the International Physical Activity Questionnaire (IPAQ). Results: The questionnaire was completed by 338 persons with either T1DM (57.1%) or T2DM (42.9%) (females: 56.2%, males: 42.0%, gender diverse persons: 1.8%) of all age groups (at least 18 years). In total, 80.5% of respondents were aware of the current physical activity recommendations. Among the respondents, 58% reported meeting the recommendations for endurance-type physical activity, while only 30.5% reported meeting those for strength training. The three most frequently cited barriers to physical activity were lack of time, lack of motivation and current state of health. Supporting factors included coverage of costs, availability of exercise programs in close proximity to the patient’s home and target group specific exercise programs. Conclusions: The results imply that many individuals with DM in Germany do not meet ADA’s physical activity recommendations, especially considering that self-reports often overestimate actual behavior. In particular, the actual number of individuals who regularly engage in strength training may be too low. There is a clear need to better communicate the benefits of different forms of physical training and to provide physical activity programs aligned with patients’ individual needs. Full article
29 pages, 3012 KiB  
Article
Investigating Multi-Omic Signatures of Ethnicity and Dysglycaemia in Asian Chinese and European Caucasian Adults: Cross-Sectional Analysis of the TOFI_Asia Study at 4-Year Follow-Up
by Saif Faraj, Aidan Joblin-Mills, Ivana R. Sequeira-Bisson, Kok Hong Leiu, Tommy Tung, Jessica A. Wallbank, Karl Fraser, Jennifer L. Miles-Chan, Sally D. Poppitt and Michael W. Taylor
Metabolites 2025, 15(8), 522; https://doi.org/10.3390/metabo15080522 (registering DOI) - 1 Aug 2025
Abstract
Background: Type 2 diabetes (T2D) is a global health epidemic with rising prevalence within Asian populations, particularly amongst individuals with high visceral adiposity and ectopic organ fat, the so-called Thin-Outside, Fat-Inside phenotype. Metabolomic and microbiome shifts may herald T2D onset, presenting potential biomarkers [...] Read more.
Background: Type 2 diabetes (T2D) is a global health epidemic with rising prevalence within Asian populations, particularly amongst individuals with high visceral adiposity and ectopic organ fat, the so-called Thin-Outside, Fat-Inside phenotype. Metabolomic and microbiome shifts may herald T2D onset, presenting potential biomarkers and mechanistic insight into metabolic dysregulation. However, multi-omics datasets across ethnicities remain limited. Methods: We performed cross-sectional multi-omics analyses on 171 adults (99 Asian Chinese, 72 European Caucasian) from the New Zealand-based TOFI_Asia cohort at 4-years follow-up. Paired plasma and faecal samples were analysed using untargeted metabolomic profiling (polar/lipid fractions) and shotgun metagenomic sequencing, respectively. Sparse multi-block partial least squares regression and discriminant analysis (DIABLO) unveiled signatures associated with ethnicity, glycaemic status, and sex. Results: Ethnicity-based DIABLO modelling achieved a balanced error rate of 0.22, correctly classifying 76.54% of test samples. Polar metabolites had the highest discriminatory power (AUC = 0.96), with trigonelline enriched in European Caucasians and carnitine in Asian Chinese. Lipid profiles highlighted ethnicity-specific signatures: Asian Chinese showed enrichment of polyunsaturated triglycerides (TG.16:0_18:2_22:6, TG.18:1_18:2_22:6) and ether-linked phospholipids, while European Caucasians exhibited higher levels of saturated species (TG.16:0_16:0_14:1, TG.15:0_15:0_17:1). The bacteria Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, and Enterocloster bolteae characterised Asian Chinese participants, while Oscillibacter sp. and Clostridium innocuum characterised European Caucasians. Cross-omic correlations highlighted negative correlations of Phocaeicola vulgatus with amino acids (r = −0.84 to −0.76), while E. ramosum and C. innocuum positively correlated with long-chain triglycerides (r = 0.55–0.62). Conclusions: Ethnicity drove robust multi-omic differentiation, revealing distinctive metabolic and microbial profiles potentially underlying the differential T2D risk between Asian Chinese and European Caucasians. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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16 pages, 604 KiB  
Article
Once-Weekly Semaglutide Improves Body Composition in Spanish Obese Adults with Type 2 Diabetes: A 48-Week Prospective Real-Life Study
by Irene Caballero-Mateos, Cristóbal Morales-Portillo and Beatriz González Aguilera
J. Clin. Med. 2025, 14(15), 5434; https://doi.org/10.3390/jcm14155434 (registering DOI) - 1 Aug 2025
Abstract
Objective: The objective of this study was to assess changes in body composition, with a specific focus on fat mass (FM) and fat-free mass (FFM), in obese adults with type 2 diabetes (T2D) treated with once-weekly (OW) subcutaneous (s.c.) semaglutide. Methods: This was [...] Read more.
Objective: The objective of this study was to assess changes in body composition, with a specific focus on fat mass (FM) and fat-free mass (FFM), in obese adults with type 2 diabetes (T2D) treated with once-weekly (OW) subcutaneous (s.c.) semaglutide. Methods: This was a single-center, 12-month, real-world, ambispective study (6-month prospective and 6-month retrospective). Body composition parameters were assessed via segmental multifrequency bioelectrical impedance analysis (SMF-BIA). Results: A total of 117 patients with DM2, with a median age of 56 years, a median HbA1c level of 9.4%, and a median body weight of 102.5 kg, were included in the study. The median body weight, body fat mass, and visceral fat significantly decreased at 6 months, with values of −9.3, −7.5, and −1.8 kg, respectively. There were further reductions from 6 to 12 months, albeit at a slower rate. The median skeletal muscle mass significantly decreased at 6 months (−1.2 kg), although no further significant reductions were observed at 12 months. Conclusions: OW s.c. semaglutide for 12 months significantly improved body composition parameters, mainly at the expense of fat mass loss, with the preservation of skeletal muscle mass. These changes are clinically meaningful, since they impact general metabolic health and are associated with improvements in metabolic control and clinical parameters associated with renal and CV risks, as well as presumable improvements in quality of life. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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30 pages, 4423 KiB  
Review
Overview of Fatty Acids and Volatiles in Selected Nuts: Their Composition and Analysis
by Gbolahan Alagbe, Klara Urbanova and Olajumoke Alagbe
Processes 2025, 13(8), 2444; https://doi.org/10.3390/pr13082444 (registering DOI) - 1 Aug 2025
Abstract
Nuts are nutrient-dense foods recognized for their complex chemical composition and associated health benefits. This review provides a comprehensive overview of the botanical classification, morphology, production, and consumption patterns of key nut species, including walnuts, almonds, pistachios, pecans, peanuts, cashews, bitter kola, and [...] Read more.
Nuts are nutrient-dense foods recognized for their complex chemical composition and associated health benefits. This review provides a comprehensive overview of the botanical classification, morphology, production, and consumption patterns of key nut species, including walnuts, almonds, pistachios, pecans, peanuts, cashews, bitter kola, and kola nuts. It emphasizes the fatty acid profiles, noting that palmitic acid (C16:0) is the predominant saturated fatty acid, while oleic acid (C18:1) and linoleic acid (C18:2) are the most abundant monounsaturated and polyunsaturated fatty acids, respectively. The review also details various analytical techniques employed for extracting and characterizing bioactive compounds, which are crucial for assessing nut quality and health benefits. Methods such as Soxhlet extraction, solid-phase microextraction (SPME), supercritical fluid extraction (SFE), gas chromatography (GC-FID and GC-MS), and high-performance liquid chromatography (HPLC) are highlighted. Furthermore, it discusses scientific evidence linking nut consumption to antioxidant and anti-inflammatory properties, improved cardiovascular health, and a reduced risk of type 2 diabetes, establishing nuts as important components in a healthy diet. This review underscores the role of nuts as functional foods and calls for standardized methodologies in future lipidomic and volatilomic studies. Full article
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44 pages, 1261 KiB  
Review
Human-Induced Pluripotent Stem Cells (iPSCs) for Disease Modeling and Insulin Target Cell Regeneration in the Treatment of Insulin Resistance: A Review
by Sama Thiab, Juberiya M. Azeez, Alekya Anala, Moksha Nanda, Somieya Khan, Alexandra E. Butler and Manjula Nandakumar
Cells 2025, 14(15), 1188; https://doi.org/10.3390/cells14151188 (registering DOI) - 1 Aug 2025
Abstract
Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired [...] Read more.
Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed. Full article
(This article belongs to the Special Issue Advances in Human Pluripotent Stem Cells)
23 pages, 888 KiB  
Article
Correlations Between Coffee Intake, Glycemic Control, Cardiovascular Risk, and Sleep in Type 2 Diabetes and Hypertension: A 12-Month Observational Study
by Tatiana Palotta Minari, José Fernando Vilela-Martin, Juan Carlos Yugar-Toledo and Luciana Pellegrini Pisani
Biomedicines 2025, 13(8), 1875; https://doi.org/10.3390/biomedicines13081875 (registering DOI) - 1 Aug 2025
Abstract
Background: The consumption of coffee has been widely debated regarding its effects on health. This study aims to analyze the correlations between daily coffee intake and sleep, blood pressure, anthropometric measurements, and biochemical markers in individuals with type 2 diabetes (T2D) and hypertension [...] Read more.
Background: The consumption of coffee has been widely debated regarding its effects on health. This study aims to analyze the correlations between daily coffee intake and sleep, blood pressure, anthropometric measurements, and biochemical markers in individuals with type 2 diabetes (T2D) and hypertension over a 12-month period. Methods: An observational study was conducted with 40 participants with T2D and hypertension, comprising 20 females and 20 males. Participants were monitored for their daily coffee consumption over a 12-month period, being assessed every 3 months. Linear regression was utilized to assess interactions and relationships between variables, providing insights into potential predictive associations. Additionally, correlation analysis was performed using Pearson’s and Spearman’s tests to evaluate the strength and direction of linear and non-linear relationships. Statistical significance was set at p < 0.05. Results: Significant changes were observed in fasting blood glucose (FBG), glycated hemoglobin (HbA1c), body weight, body mass index, sleep duration, nocturnal awakenings, and waist-to-hip ratio (p < 0.05) over the 12-month study in both sexes. No significant differences were noted in the remaining parameters (p > 0.05). The coffee consumed by the participants was of the “traditional type” and contained sugar (2g per cup) for 100% of the participants. An intake of 4.17 ± 0.360 cups per day was found at baseline and 5.41 ± 0.316 cups at 12 months (p > 0.05). Regarding correlation analysis, a higher coffee intake was significantly associated with shorter sleep duration in women (r = −0.731; p = 0.037). Conversely, greater coffee consumption correlated with lower LDL cholesterol (LDL-C) levels in women (r = −0.820; p = 0.044). Additionally, a longer sleep duration was linked to lower FBG (r = -0.841; p = 0.031), HbA1c (r = -0.831; p = 0.037), and LDL-C levels in women (r = -0.713; p = 0.050). No significant correlations were observed for the other parameters in both sexes (p > 0.05). Conclusions: In women, coffee consumption may negatively affect sleep duration while potentially offering beneficial effects on LDL-C levels, even when sweetened with sugar. Additionally, a longer sleep duration in women appears to be associated with improvements in FBG, HbA1c, and LDL-C. These correlations emphasize the importance of a balanced approach to coffee consumption, weighing both its potential health benefits and drawbacks in postmenopausal women. However, since this study does not establish causality, further randomized clinical trials are warranted to investigate the underlying mechanisms and long-term implications—particularly in the context of T2D and hypertension. Full article
(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights (3rd Edition))
13 pages, 1192 KiB  
Article
Serum Endocan Levels Correlate with Metabolic Syndrome Severity and Endothelial Dysfunction: A Cross-Sectional Study Using the MetS-Z Score
by Mehmet Vatansever, Selçuk Yaman, Ahmet Cimbek, Yılmaz Sezgin and Serap Ozer Yaman
Metabolites 2025, 15(8), 521; https://doi.org/10.3390/metabo15080521 (registering DOI) - 1 Aug 2025
Abstract
Background: Metabolic syndrome (MetS) is a complex clinical condition characterized by the coexistence of interrelated metabolic abnormalities that significantly increase the risk of cardiovascular diseases and type 2 diabetes mellitus. Endocan—an endothelial cell-specific molecule—is considered a biomarker of endothelial dysfunction and inflammation. This [...] Read more.
Background: Metabolic syndrome (MetS) is a complex clinical condition characterized by the coexistence of interrelated metabolic abnormalities that significantly increase the risk of cardiovascular diseases and type 2 diabetes mellitus. Endocan—an endothelial cell-specific molecule—is considered a biomarker of endothelial dysfunction and inflammation. This study aimed to evaluate the relationship between serum endocan levels and the severity of MetS, assessed using the MetS-Z score. Methods: This study included 120 patients with MetS and 50 healthy controls. MetS was diagnosed according to the NCEP-ATP III criteria. MetS-Z scores were calculated using the MetS Severity Calculator. Serum levels of endocan, sICAM-1, and sVCAM-1 were measured using the ELISA method. Results: Serum levels of endocan, sICAM-1, and sVCAM-1 were significantly higher in the MetS group compared to the control group (all p < 0.001). When the MetS group was divided into tertiles based on MetS-Z scores, stepwise and statistically significant increases were observed in the levels of endocan and other endothelial markers from the lowest to highest tertile (p < 0.0001). Correlation analysis revealed a strong positive association between the MetS-Z score and serum endocan levels (r = 0.584, p < 0.0001). ROC curve analysis showed that endocan has high diagnostic accuracy for identifying MetS (AUC = 0.967, p = 0.0001), with a cutoff value of >88.0 ng/L. Conclusions: Circulating levels of endocan were significantly increased in MetS and were associated with the severity of MetS, suggesting that endocan may play a role in the cellular response to endothelial dysfunction-related injury in patients with MetS. Full article
(This article belongs to the Special Issue Lipid Metabolism Disorders in Obesity)
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14 pages, 1451 KiB  
Article
Diabetes Has Minimal Effect on High Gastrointestinal Symptom Burden in Exocrine Pancreatic Insufficiency Based on EPI/PEI-SS Scores
by Dana M. Lewis
J. Clin. Med. 2025, 14(15), 5422; https://doi.org/10.3390/jcm14155422 (registering DOI) - 1 Aug 2025
Abstract
Background: Exocrine pancreatic insufficiency (EPI or PEI) may be prevalent in as many as 3 of 10 people with diabetes due to exocrine pancreatic function being reduced as early as the time of diagnosis. EPI can be treated with pancreatic enzyme replacement therapy [...] Read more.
Background: Exocrine pancreatic insufficiency (EPI or PEI) may be prevalent in as many as 3 of 10 people with diabetes due to exocrine pancreatic function being reduced as early as the time of diagnosis. EPI can be treated with pancreatic enzyme replacement therapy (PERT), but the symptom burden of EPI remains high and improved screening and diagnosis methods are needed. Methods: An online survey (n = 324) evaluated the gastrointestinal symptom experiences of people with (n = 155) and without (n = 169) EPI using a novel symptom tool, the Exocrine Pancreatic Insufficiency Symptom Score (EPI/PEI-SS). A large sub-group (n = 120) of people with diabetes with EPI (Type 1, n = 14, Type 2, n = 20) or without EPI (Type 1, n = 78; Type 2; n = 6) was characterized and compared to those without diabetes (n = 204) in a sub-analysis of the larger EPI/PEI-SS study. Results: The symptom burden of EPI is similar, irrespective of diabetes. Like those without diabetes, people with type 1 diabetes with EPI had a statistically significant (p < 0.001) higher mean score (range 0–225) on the EPI/PEI-SS (100.86, SD: 48.92) than people with T1D without EPI (31.59, SD: 28.25), distinct from other GI conditions (p < 0.001). Similar patterns occurred in those with T2D. Conclusions: High EPI/PEI-SS scores seem to distinguish between likely EPI and other GI conditions among people with diabetes, and the EPI/PEI-SS should be further studied as a possible screening method for EPI at a population level. It should also be evaluated as a tool to aid individuals with diabetes in tracking changes to EPI symptoms over time based on PERT titration. Full article
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19 pages, 397 KiB  
Review
Effects of Blood-Glucose Lowering Therapies on Body Composition and Muscle Outcomes in Type 2 Diabetes: A Narrative Review
by Ioana Bujdei-Tebeică, Doina Andrada Mihai, Anca Mihaela Pantea-Stoian, Simona Diana Ștefan, Claudiu Stoicescu and Cristian Serafinceanu
Medicina 2025, 61(8), 1399; https://doi.org/10.3390/medicina61081399 (registering DOI) - 1 Aug 2025
Abstract
Background and Objectives: The management of type 2 diabetes (T2D) extends beyond glycemic control, requiring a more global strategy that includes optimization of body composition, even more so in the context of sarcopenia and visceral adiposity, as they contribute to poor outcomes. [...] Read more.
Background and Objectives: The management of type 2 diabetes (T2D) extends beyond glycemic control, requiring a more global strategy that includes optimization of body composition, even more so in the context of sarcopenia and visceral adiposity, as they contribute to poor outcomes. Past reviews have typically been focused on weight reduction or glycemic effectiveness, with limited inclusion of new therapies’ effects on muscle and fat distribution. In addition, the emergence of incretin-based therapies and dual agonists such as tirzepatide requires an updated synthesis of their impacts on body composition. This review attempts to bridge the gap by taking a systematic approach to how current blood-glucose lowering therapies affect lean body mass, fat mass, and the risk of sarcopenia in T2D patients. Materials and Methods: Between January 2015 and March 2025, we conducted a narrative review by searching the PubMed, Scopus, and Web of Science databases for English-language articles. The keywords were combinations of the following: “type 2 diabetes,” “lean body mass,” “fat mass,” “body composition,” “sarcopenia,” “GLP-1 receptor agonists,” “SGLT2 inhibitors,” “tirzepatide,” and “antidiabetic pharmacotherapy.” Reference lists were searched manually as well. The highest precedence was assigned to studies that aimed at adult type 2 diabetic subjects and reported body composition results. Inclusion criteria for studies were: (1) type 2 diabetic mellitus adult patients and (2) reporting measures of body composition (e.g., lean body mass, fat mass, or muscle function). We prioritized randomized controlled trials and large observational studies and excluded mixed diabetic populations, non-pharmacological interventions only, and poor reporting of body composition. Results: Metformin was widely found to be weight-neutral with minimal effects on muscle mass. Insulin therapy, being an anabolic hormone, often leads to fat mass accumulation and increases the risk of sarcopenic obesity. Incretin-based therapies induced substantial weight loss, mostly from fat mass. Notable results were observed in studies with tirzepatide, demonstrating superior reduction not only in fat mass, but also in visceral fat. Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) promote fat loss but are associated with a small yet significant decrease in lean muscle mass. Conclusions: Blood-glucose lowering therapies demonstrated clinically relevant effects on body composition. Treatment should be personalized, balancing glycemic control, cardiovascular, and renal benefits, together with optimal impact on muscle mass along with glycemic, cardiovascular, and renal benefits. Full article
(This article belongs to the Section Endocrinology)
15 pages, 245 KiB  
Article
Becoming Autonomous and Integrating Insulin Pump Therapy into Life: A Qualitative Analysis of Adolescent Experiences with Type 1 Diabetes Management
by Eleni C. Tzavela, Lydia Kossiva, Irine-Ikbale Sakou, George Paltoglou, Adamantini Plarinou, Spyridon Karanasios and Kyriaki Karavanaki
Diabetology 2025, 6(8), 76; https://doi.org/10.3390/diabetology6080076 (registering DOI) - 1 Aug 2025
Abstract
Objectives: This study explored perceptions, experiences, and outcomes associated with the choice of insulin therapies among pediatric patients with type 1 diabetes mellitus (T1D). Methods: This study included 20 adolescents (8 male and 12 female) with T1D, with a mean age of 15.05 [...] Read more.
Objectives: This study explored perceptions, experiences, and outcomes associated with the choice of insulin therapies among pediatric patients with type 1 diabetes mellitus (T1D). Methods: This study included 20 adolescents (8 male and 12 female) with T1D, with a mean age of 15.05 ± 0.91 years, a mean diabetes duration of 5.19 ± 1.2 years, and a mean most recent HbA1c of 7.03 ± 0.16%. Ten of the participants were using an insulin pump (n = 10) and another 10 had either refused (n = 7) or discontinued (n = 3) insulin pump therapy. A qualitative inductive method was employed, using in-depth individual interviews. The interview material was transcribed verbatim and grounded theory was used to analyze the verbal material. Results: Four main thematic categories were identified from the narrations that captured both common and divergent perceptions of insulin pump users versus non-users: (1) adjusting to the lifelong diagnosis, (2) exposing diabetes versus hiding it, (3) becoming autonomous and integrating insulin pump therapy into daily life, and (4) worrying over the pump. The third theme, capturing autonomy and integration, surfaced as the core thematic category of this study. Conclusions: This grounded theory study revealed that, by using insulin pump therapy, adolescent T1D patients can enhance their autonomy and facilitate the integration of insulin treatment into their life. This study identified processes that inform diabetes education and contribute to ameliorating gaps in the uptake and maintenance of pump therapy in pediatric care. Full article
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12 pages, 1302 KiB  
Article
Exploring the Relationship Between Insulin Resistance, Liver Health, and Restrictive Lung Diseases in Type 2 Diabetes
by Mani Roshan, Christian Mudrack, Alba Sulaj, Ekaterina von Rauchhaupt, Thomas Fleming, Lukas Schimpfle, Lukas Seebauer, Viktoria Flegka, Valter D. Longo, Elisabeth Kliemank, Stephan Herzig, Anna Hohneck, Zoltan Kender, Julia Szendroedi and Stefan Kopf
J. Pers. Med. 2025, 15(8), 340; https://doi.org/10.3390/jpm15080340 (registering DOI) - 1 Aug 2025
Abstract
Background: Restrictive lung disease (RLD) is a potential complication in type 2 diabetes (T2D), but its relationship with insulin resistance and liver-related metabolic dysfunction remains unclear. This study evaluated the association between lung function and metabolic markers in T2D and retrospectively assessed [...] Read more.
Background: Restrictive lung disease (RLD) is a potential complication in type 2 diabetes (T2D), but its relationship with insulin resistance and liver-related metabolic dysfunction remains unclear. This study evaluated the association between lung function and metabolic markers in T2D and retrospectively assessed whether metabolic improvements from dietary intervention were accompanied by changes in lung function. Methods: This cross-sectional analysis included 184 individuals (101 with T2D, 33 with prediabetes, and 50 glucose-tolerant individuals). Lung function parameters—vital capacity (VC), total lung capacity by plethysmography (TLC-B), and diffusion capacity for carbon monoxide (TLCO)—were assessed alongside metabolic markers including HOMA2-IR, fatty liver index (FLI), NAFLD score, and Fibrosis-4 index (FIB-4). In a subset of 54 T2D participants, lung function was reassessed after six months following either a fasting-mimicking diet (FMD, n = 14), Mediterranean diet (n = 13), or no dietary intervention (n = 27). Results: T2D participants had significantly lower VC and TLC-B compared to glucose-tolerant and prediabetic individuals, with 18–21% falling below clinical thresholds for RLD. Lung volumes were negatively correlated with HOMA2-IR, FLI, NAFLD score, and FIB-4 across the cohort and within the T2D group. Although the FMD intervention led to significant improvements in HOMA2-IR and FLI, no corresponding changes in lung function were observed over the six-month period. Conclusions: Restrictive lung impairment in T2D is associated with insulin resistance and markers of liver steatosis and fibrosis. While short-term dietary interventions can improve metabolic parameters, their effect on lung function may require a longer duration or additional interventions and targeted follow-up. These findings highlight the relevance of pulmonary assessment in individuals with metabolic dysfunction. Full article
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11 pages, 245 KiB  
Review
The Impact of Insulin Resistance on Lung Volume Through Right Ventricular Dysfunction in Diabetic Patients—Literature Review
by Daniel Radu, Oana-Andreea Parlițeanu, Andra-Elena Nica, Cristiana Voineag, Octavian-Sabin Alexe, Alexandra Maria Cristea, Livia Georgescu, Roxana Maria Nemeș, Andreea Taisia Tiron and Alexandra Floriana Nemeș
J. Pers. Med. 2025, 15(8), 336; https://doi.org/10.3390/jpm15080336 (registering DOI) - 1 Aug 2025
Abstract
Insulin resistance (IR), a core component in the development of type 2 diabetes mellitus (T2DM), is increasingly recognized for its role in cardiovascular and pulmonary complications. This review explores the relationship between IR, right ventricular dysfunction (RVD), and decreased lung volume in patients [...] Read more.
Insulin resistance (IR), a core component in the development of type 2 diabetes mellitus (T2DM), is increasingly recognized for its role in cardiovascular and pulmonary complications. This review explores the relationship between IR, right ventricular dysfunction (RVD), and decreased lung volume in patients with T2DM. Emerging evidence suggests that IR contributes to early structural and functional alterations in the right ventricle, independent of overt cardiovascular disease. The mechanisms involved include oxidative stress, inflammation, dyslipidemia, and obesity—factors commonly found in metabolic syndrome and T2DM. These pathophysiological changes compromise right ventricular contractility, leading to reduced pulmonary perfusion and respiratory capacity. RVD has been associated with chronic lung disease, pulmonary hypertension, and obstructive sleep apnea, all of which are prevalent in the diabetic population. As RVD progresses, it can result in impaired gas exchange, interstitial pulmonary edema, and exercise intolerance—highlighting the importance of early recognition and management. Therapeutic strategies should aim to improve insulin sensitivity and cardiac function through lifestyle interventions, pharmacological agents such as SGLT2 inhibitors and GLP-1/GIP analogs, and routine cardiac monitoring. These approaches may help slow the progression of RVD and its respiratory consequences. Considering the global burden of diabetes and obesity, and the growing incidence of related complications, further research is warranted to clarify the mechanisms linking IR, RVD, and respiratory dysfunction. Understanding this triad will be crucial for developing targeted interventions that improve outcomes and quality of life in affected patients. Full article
(This article belongs to the Section Mechanisms of Diseases)
17 pages, 4219 KiB  
Article
Identification of Differentially Expressed Genes and Pathways in Non-Diabetic CKD and Diabetic CKD by Integrated Human Transcriptomic Bioinformatics Analysis
by Clara Barrios, Marta Riera, Eva Rodríguez, Eva Márquez, Jimena del Risco, Melissa Pilco, Jorge Huesca, Ariadna González, Claudia Martyn, Jordi Pujol, Anna Buxeda and Marta Crespo
Int. J. Mol. Sci. 2025, 26(15), 7421; https://doi.org/10.3390/ijms26157421 (registering DOI) - 1 Aug 2025
Abstract
Chronic kidney disease (CKD) is a heterogeneous condition with various etiologies, including type 2 diabetes mellitus (T2D), hypertension, and autoimmune disorders. Both diabetic CKD (CKD_T2D) and non-diabetic CKD (CKD_nonT2D) share overlapping clinical features, but understanding the molecular mechanisms underlying each subtype and distinguishing [...] Read more.
Chronic kidney disease (CKD) is a heterogeneous condition with various etiologies, including type 2 diabetes mellitus (T2D), hypertension, and autoimmune disorders. Both diabetic CKD (CKD_T2D) and non-diabetic CKD (CKD_nonT2D) share overlapping clinical features, but understanding the molecular mechanisms underlying each subtype and distinguishing diabetic from non-diabetic forms remain poorly defined. To identify differentially expressed genes (DEGs) and enriched biological pathways between CKD_T2D and CKD_nonT2D cohorts, including autoimmune (CKD_nonT2D_AI) and hypertensive (CKD_nonT2D_HT) subtypes, through integrative transcriptomic analysis. Publicly available gene expression datasets from human glomerular and tubulointerstitial kidney tissues were curated and analyzed from GEO and ArrayExpress. Differential expression analysis and Gene Set Enrichment Analysis (GSEA) were conducted to assess cohort-specific molecular signatures. A considerable overlap in DEGs was observed between CKD_T2D and CKD_nonT2D, with CKD_T2D exhibiting more extensive gene expression changes. Hypertensive-CKD shared greater transcriptomic similarity with CKD_T2D than autoimmune-CKD. Key DEGs involved in fibrosis, inflammation, and complement activation—including Tgfb1, Timp1, Cxcl6, and C1qa/B—were differentially regulated in diabetic samples, where GSEA revealed immune pathway enrichment in glomeruli and metabolic pathway enrichment in tubulointerstitium. The transcriptomic landscape of CKD_T2D reveals stronger immune and metabolic dysregulation compared to non-diabetic CKD. These findings suggest divergent pathological mechanisms and support the need for tailored therapeutic approaches. Full article
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