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Akomolafe SF, Ajayi OO, Agboola OE, Adewale OO. Comparative evaluation of the antidiabetic potential of three varieties of Ipomoea batatas L.. Toxicol Rep 2025; 14:102015. [PMID: 40230512 PMCID: PMC11995110 DOI: 10.1016/j.toxrep.2025.102015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 03/13/2025] [Accepted: 03/25/2025] [Indexed: 04/16/2025] Open
Abstract
Sweet potato (Ipomoea batatas L.) is a nutrient-dense tuber often used in traditional diabetic treatment. This research compares the antidiabetic potential of three sweet potato varieties: orange-fleshed (OFSP), purple-peel white-fleshed (PPWSP), and white-peel white-fleshed (WPWSP), utilising in vitro and in vivo techniques. Sweet potatoes (OFSP, PPWSP, and WPWSP) boiled at 100°C for 20 minutes were incorporated into formulated diets and administered to streptozotocin-induced diabetic rats for 14 days. Aqueous extracts of the diets were tested in vitro for antioxidants and phytochemicals. Glycaemic control parameters, lipid profiles, oxidative stress indicators, and pancreatic histology were investigated. Gene expression analysis was performed on critical diabetes-related pathways. OFSP showed significant strong anti-diabetic benefits, including better glycemic control, weight maintenance, lower HOMA-IR scores, and lowered α-amylase and α-glucosidase activity. OFSP-fed rats had higher insulin, glycogen, and hexokinase activity than those given PPWSP and WPWSP. OFSP decreased mRNA expression of DPP-4 while increasing GLP-1 expression. OFSP also improved lipid profiles, increasing HDLc while decreasing LDLc and triglycerides more than other varieties. Histopathological examination revealed restorative effects in pancreatic beta cells. OFSP demonstrated more pronounced antidiabetic effects compared to PPWSP and WPWSP, particularly in terms of glycemic control, insulin regulation, and lipid profile improvement. These findings suggest that OFSP may offer significant potential for diabetes management. However, further clinical studies are needed to validate these results and explore the practical dietary applications of OFSP in diabetes control.
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Affiliation(s)
- Seun F. Akomolafe
- Department of Biochemistry, Ekiti State University, Ado Ekiti, Ekiti State, PMB 5363, Nigeria
- Department of Pharmaceutical Biology, Faculty of Pharmacy, Medical University of Warsaw, ul. Banacha 1, Warsaw 02-097, Poland
| | - Oluwadamilare O. Ajayi
- Department of Biochemistry, Ekiti State University, Ado Ekiti, Ekiti State, PMB 5363, Nigeria
| | - Oluwaseun E. Agboola
- Institute for Drug Research and Development, Afe Babalola University, Ado Ekiti, Nigeria
- DamSem Scientific Laboratory and Research, Oke-Ila, Ado Ekiti, Nigeria
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Lim BSY, Chen M, Li H, Li L. Metformin use in prediabetes: A review of evidence and a focus on metabolic features among peri-menopausal women. Diabetes Obes Metab 2025; 27 Suppl 3:3-15. [PMID: 40329646 PMCID: PMC12094222 DOI: 10.1111/dom.16442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 04/23/2025] [Accepted: 04/23/2025] [Indexed: 05/08/2025]
Abstract
The prevalence of prediabetes has more than doubled over the past two decades. Although hormones associated with the menstrual cycle may offer some protection against diabetes by enhancing insulin sensitivity and suppressing gluconeogenesis, the prevalence of diabetes among women remains high at 10.5%. Notably, among the perimenopausal population, the prevalence catches up to-and even surpasses-that of men starting from the 70-74 age group, according to the 2021 International Diabetes Federation (IDF) report. This narrative review examines the benefits and potential risks of metformin across diverse populations, with a particular emphasis on women in the perimenopausal phase. Metformin's interaction with hormonal regulation significantly influences both its therapeutic efficacy and long-term side effect profile, contributing to sex-specific differences in treatment response. Consequently, its effectiveness varies among women at different stages of menopause, potentially due to differential impacts on inflammatory markers and modulation of the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-thyroid (HPT) axes. Emerging evidence also highlights metformin's potential in managing conditions such as polycystic ovary syndrome (PCOS), breast tissue inflammation and endometrial disorders within this demographic. Given these potential and multifaceted benefits, this review highlights the need for further randomized controlled trials (RCTs) to investigate metformin's role among perimenopausal and menopausal women and to better understand how menopausal status may influence its efficacy. PLAIN LANGUAGE SUMMARY: The number of people with prediabetes has more than doubled in the last 20 years. By 2021, about 720 million people worldwide were living with this condition, and that number is expected to reach 1 billion by 2045. While hormones that fluctuate with the menstrual cycle might help protect against diabetes, the overall rate of diabetes among women is still concerning, at 10.5%. For women going through menopause, the situation is even more serious. From the age of 70 to 74, the rates of diabetes in women surpass those in men. This may be because menopause reduces levels of protective hormones like estrogen and progesterone, which help guard against type 2 diabetes (T2D). Despite this growing issue, there hasn't been much research focused on prediabetes in women going through menopause and how the changes in hormones might affect treatment guidelines. To address this lack of information, our review focused on the use of metformin for women in the perimenopausal stage with prediabetes, aiming to help prevent them from developing T2D in the future. We gathered insights from recent clinical trials to summarize the benefits and risks of metformin for various groups, particularly perimenopausal women. Our findings indicate that metformin can be effective for managing prediabetes, although opinions vary. It's currently the only diabetes medication recommended for prediabetes by the American Diabetes Association (ADA), supported by significant studies like the Diabetes Prevention Program (DPP) and the Coronary Endothelial Dysfunction Multicentre Prospective Study (CODYCE study). Metformin's effectiveness seems to increase when combined with lifestyle changes, such as diet and exercise. Some challenges exist, though, like concerns that it might only work for those at a high risk of developing T2D, potential side effects, and the availability of other options, such as lifestyle adjustments or a new medication called tirzepatide. Still, many experts argue that metformin remains valuable because it allows for early intervention, particularly when lifestyle changes alone may not be enough. We also found that metformin might work differently for men and women due to variations in hormone interactions, differing gut bacteria, and weight-related factors that can influence its effectiveness. Interestingly, metformin seems to work better for women who have not yet gone through menopause. This might be because it helps with weight loss and reduces inflammation, which are important for postmenopausal health. Moreover, metformin has shown promise in addressing other health issues that postmenopausal women may face, such as inflammation in breast tissue, certain types of cancer, endometrial problems (as an alternative to hormone therapy), and polycystic ovarian syndrome (PCOS). In conclusion, our review stresses the importance of creating specific guidelines for managing prediabetes (e.g., metformin therapy) in the perimenopausal population. Understanding how sex hormones interact with blood sugar control is crucial for developing effective treatments tailored to women at different stages of menopause.
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Affiliation(s)
- Beth Shi Yu Lim
- Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
| | - Muzi Chen
- Faculty of ScienceNational University of SingaporeSingaporeSingapore
| | - Hung‐Yuan Li
- Division of Endocrinology and Metabolism, Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
| | - Ling‐Jun Li
- Department of Obstetrics & GynaecologyYong Loo Lin School of Medicine, National University of SingaporeSingaporeSingapore
- Global Centre for Asian Women's Health, Human Potential Translational Research ProgrammeYong Loo Lin School of Medicine, National University of SingaporeSingaporeSingapore
- NUS Bia‐Echo Asia Centre for Reproductive Longevity and Equality (ACRLE)Yong Loo Lin School of Medicine, National University of SingaporeSingaporeSingapore
- Institute for Human Development & Potential (iHPP)Agency for Sciences, Technology & Research (A*STAR)SingaporeSingapore
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Xing JH, Yu Y, Teng L, Hui XY, Guo WG. Association of Blood Heavy Metals with Diabetic Foot Ulcers in U.S. Adults with Diabetes: Insights from the 1999-2004 NHANES Data. Diabetes Ther 2025; 16:1255-1266. [PMID: 40153229 PMCID: PMC12085517 DOI: 10.1007/s13300-025-01730-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Accepted: 03/14/2025] [Indexed: 03/30/2025] Open
Abstract
INTRODUCTION Diabetic foot ulcers (DFU) are serious complications of diabetes. These ulcers significantly increase the risk of amputations. Many studies have examined how blood heavy metals affect insulin secretion in diabetes. However, research linking blood heavy metal exposure to DFU is limited. This study aims to explore the connection between blood heavy metal exposure and DFU in people with diabetes. METHODS This cross-sectional study used data from the 1999-2004 cycle of the National Health and Nutrition Examination Survey (NHANES). Researchers measured blood levels of lead (Pb) and cadmium (Cd) using inductively coupled plasma mass spectrometry (ICP-MS). Four logistic regression models assessed the relationship between blood heavy metals and the prevalence of DFU. The models adjusted for potential confounding factors. Additionally, smooth curve fitting and piecewise regression analyses were conducted to investigate the correlation further. Subgroup analyses and interaction tests helped evaluate consistency across the general population. RESULTS A total of 1664 participants aged 40 years or older with diabetes were included in the final analysis. The average age is 64.66 ± 11.79 years, with 52.52% being male and 47.48% being female. Among these individuals, 135 (8.11%) were diagnosed with DFU. Statistical modeling revealed a significant positive correlation between blood cadmium (Cd) levels and the prevalence of DFU. Specifically, model 4, which was the fully adjusted model, indicated that for each unit increase in blood Cd level, there was a corresponding 64% increase in DFU prevalence [OR = 1.64; 95% CI (1.42-1.89), p = 0.004]. Further analysis through smooth curve fitting demonstrated a significant linear relationship between blood Cd levels and DFU prevalence. CONCLUSIONS This study identified a positive correlation between blood cadmium (Cd) levels and the prevalence of DFU. These results suggest that monitoring blood Cd levels in patients with diabetes during follow-up may be important for preventing the development of DFU. However, further prospective studies are necessary to provide additional evidence.
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Affiliation(s)
- Jia-Hao Xing
- Heilongjiang University of Chinese Medicine, Heilongjiang, 150001, China
| | - Yang Yu
- Department of Peripheral Vascular Diseases, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, 150001, Heilongjiang, China
| | - Lin Teng
- Department of Peripheral Vascular Diseases, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, 150001, Heilongjiang, China
| | - Xue-Ying Hui
- Department of Peripheral Vascular Diseases, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, 150001, Heilongjiang, China
| | - Wei-Guang Guo
- Department of Peripheral Vascular Diseases, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, 150001, Heilongjiang, China.
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Atas E, Berchtold K, Schlederer M, Prodinger S, Sternberg F, Pucci P, Steel C, Matthews JD, James ER, Philippe C, Trachtová K, Moazzami AA, Artamonova N, Melchior F, Redmer T, Timelthaler G, Pohl EE, Turner SD, Heidegger I, Krueger M, Resch U, Kenner L. The anti-diabetic PPARγ agonist Pioglitazone inhibits cell proliferation and induces metabolic reprogramming in prostate cancer. Mol Cancer 2025; 24:134. [PMID: 40320521 PMCID: PMC12051277 DOI: 10.1186/s12943-025-02320-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 04/01/2025] [Indexed: 05/08/2025] Open
Abstract
Prostate cancer (PCa) and Type 2 diabetes (T2D) often co-occur, yet their relationship remains elusive. While some studies suggest that T2D lowers PCa risk, others report conflicting data. This study investigates the effects of peroxisome proliferator-activated receptor (PPAR) agonists Bezafibrate, Tesaglitazar, and Pioglitazone on PCa tumorigenesis. Analysis of patient datasets revealed that high PPARG expression correlates with advanced PCa and poor survival. The PPARγ agonists Pioglitazone and Tesaglitazar notably reduced cell proliferation and PPARγ protein levels in primary and metastatic PCa-derived cells. Proteomic analysis identified intrinsic differences in mTORC1 and mitochondrial fatty acid oxidation (FAO) pathways between primary and metastatic PCa cells, which were further disrupted by Tesaglitazar and Pioglitazone. Moreover, metabolomics, Seahorse Assay-based metabolic profiling, and radiotracer uptake assays revealed that Pioglitazone shifted primary PCa cells' metabolism towards glycolysis and increased FAO in metastatic cells, reducing mitochondrial ATP production. Furthermore, Pioglitazone suppressed cell migration in primary and metastatic PCa cells and induced the epithelial marker E-Cadherin in primary PCa cells. In vivo, Pioglitazone reduced tumor growth in a metastatic PC3 xenograft model, increased phosho AMPKα and decreased phospho mTOR levels. In addition, diabetic PCa patients treated with PPAR agonists post-radical prostatectomy implied no biochemical recurrence over five to ten years compared to non-diabetic PCa patients. Our findings suggest that Pioglitazone reduces PCa cell proliferation and induces metabolic and epithelial changes, highlighting the potential of repurposing metabolic drugs for PCa therapy.
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Affiliation(s)
- Emine Atas
- Department of Pathology, Medical University of Vienna, Vienna, Austria.
- Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Medical University of Vienna, Vienna, Austria.
- Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
| | | | | | | | - Felix Sternberg
- Department of Biological Sciences and Pathobiology, Unit of Physiology and Biophysics, University of Veterinary Medicine, Vienna, Austria
- Department of Nutritional Science, University of Vienna, Vienna, Austria
| | - Perla Pucci
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK
| | - Christopher Steel
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK
| | - Jamie D Matthews
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK
| | - Emily R James
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK
| | - Cécile Philippe
- Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
| | - Karolína Trachtová
- Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Medical University of Vienna, Vienna, Austria
- Central European Institute of Technology, Masaryk University, Brno, 62500, Czech Republic
| | - Ali A Moazzami
- Department of Molecular Sciences, Swedish University of Agricultural Sciences, 75007, Uppsala, Sweden
| | | | - Felix Melchior
- Department of Urology, Medical University of Innsbruck, Innsbruck, Austria
| | - Torben Redmer
- Unit of Laboratory Animal Pathology, Institute of Pathology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Gerald Timelthaler
- Center for Cancer Research, Medical University of Vienna, Vienna, Austria
| | - Elena E Pohl
- Department of Biological Sciences and Pathobiology, Unit of Physiology and Biophysics, University of Veterinary Medicine, Vienna, Austria
| | - Suzanne D Turner
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK
- Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Isabel Heidegger
- Department of Urology, Medical University of Innsbruck, Innsbruck, Austria
| | - Marcus Krueger
- Institute for Genetics, Cologne Excellence Cluster of Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany
| | - Ulrike Resch
- Center of Physiology and Pharmacology, Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria
| | - Lukas Kenner
- Department of Pathology, Medical University of Vienna, Vienna, Austria.
- Christian Doppler Laboratory for Applied Metabolomics (CDL-AM), Medical University of Vienna, Vienna, Austria.
- Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
- Unit of Laboratory Animal Pathology, Institute of Pathology, University of Veterinary Medicine Vienna, Vienna, Austria.
- Center for Biomarker Research in Medicine GmbH (CBmed), Graz, Austria.
- Department of Molecular Biology, Umeå University, Umea, Sweden.
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Licinio J, Licinio AW, Busnello JV, Ribeiro L, Gold PW, Bornstein SR, Wong ML. The emergence of chronic diseases of adulthood and middle age in the young: the COIDS (chronic inflammation, obesity, insulin resistance/type 2 diabetes, and depressive syndromes) noxious quartet of pro-inflammatory stress outcomes. Mol Psychiatry 2025:10.1038/s41380-025-03034-9. [PMID: 40316674 DOI: 10.1038/s41380-025-03034-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 04/08/2025] [Accepted: 04/15/2025] [Indexed: 05/04/2025]
Abstract
Major depression, type 2 diabetes, and essential (primary) hypertension are chronic medical and psychiatric disorders that have traditionally affected primarily adults and middle-aged individuals. However, recent decades have witnessed an increasing prevalence of these conditions among children and adolescents. For diseases that typically require prolonged exposure to risk factors to emerge in childhood and adolescence, the amount of exposure to a single risk factor would have to be exceptionally high. We advance the alternative hypothesis of multiple factors acting synergistically. Biological mechanisms underlying the response to ongoing (chronic) stress are logical candidates for being a shared pathway. In the context of persistent and synergistic psychological, social, and economic pressures, unremitting stress can lead to such disease outcomes, exerting a direct influence on the emergence of chronic disorders, and it can also contribute to obesity. Depression follows the same trajectory; therefore, we should examine it as an entity whose consequences are directly reflected in behavioral outcomes, including (over-) eating. Other contributing pathways include chronic sleep deprivation, epigenetic modifications, telomere shortening, the physical environment, pathogens, and the microbiome. We introduce here the concept of the Chronic inflammation, Obesity, Insulin resistance/type 2 diabetes, and Depressive Syndromes (COIDS) noxious quartet of pro-inflammatory stress outcomes, as an increasingly common pathophysiologic state, representing a distinct presentation of type 2 allostatic overload, with direct implications for the current chronic disease epidemic. The compounded effects of a pro-inflammatory state that is fueled by four different and co-existing sources may contribute to explain the emergence of chronic diseases of adulthood and middle age in the young. PPARγ might represent a potential translational therapeutic target for those with COIDS. We propose that highly adverse environments sustain sufficient chronic stress to bring about in the young diseases that had been previously confined to adults.
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Affiliation(s)
- Julio Licinio
- State University of New York, Upstate Medical University, 505 Irving Ave 3302, Syracuse, NY, 13210, USA.
| | - Alice W Licinio
- Vita-Salute San Raffaele University, Via Olgettina, 58, 20132, Milano, MI, Italy
| | | | - Luciana Ribeiro
- Ascension Saint Joseph - Chicago, 2900 N Lake Shore Dr, Chicago, IL, 60657, USA
| | - Philip W Gold
- Intramural Research Program, National Institute of Mental Health, NIH Clinical Center 2D-46-1284, Bethesda, MD, 20814-1284, USA
| | - Stefan R Bornstein
- Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Ma-Li Wong
- State University of New York, Upstate Medical University, 505 Irving Ave 3302, Syracuse, NY, 13210, USA.
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Hafeez S, Shakil-Ur-Rehman S, Riaz S, Hafeez S, Hafeez JS, Mumtaz H. Consensus-Driven Development of an Exercise Base Manual Programme for Prediabetic Patients: A Delphi Study. J Multidiscip Healthc 2025; 18:2461-2476. [PMID: 40330602 PMCID: PMC12051977 DOI: 10.2147/jmdh.s503455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Accepted: 03/27/2025] [Indexed: 05/08/2025] Open
Abstract
Background Prediabetes is a medical condition characterized by increased levels of glucose in the bloodstream. There are some lifestyle modifications like exercise, dietary patterns and prevention that can reverse prediabetes. Exercise plays an important role in controlling hyperglycemia and insulin sensitivity in prediabetes. Purpose The objective of the study is to develop a consensus driven exercise base manual programme for the prediabetic population using the Delphi Method. Methods A three-rounded Delphi study was conducted with 40 panelists either as Patient panelists (n = 20) or expert panelists (n=20). Round 1 included initial items selected from a systemic literature review . Initial recommendations were rated by panalists through a 5-point Likert scale. Additional items were also added by suggestion of Panelists in Round 1. Rounds 2 and 3 included all items from Round 1. All selected items were included in the final set of recommendations in Round 3 and rated as "Important" or "Very important" by at least 70% of all respondents. Descriptive data was analyzed by using SPSS version 25. Results 36 panellists (patients n = 17, professionals n = 19) completed Round 3. After three rounds of the Delphi process, panelists reached a consensus on the final version of the recommendations. Sixty-two items reached consensus in Round 1. In round 2 and 3 a total of sixty-four and sixty-three items were added, respectively. Fifty-seven of these reached consensuses in round 3. Conclusion The exercise-based manual programme developed by Modified Delphi study provided disease prevention education, physical activity and dietary recommendations to improve glycemic control in the prediabetic population. The exercise manual programme along with lifestyle modifications contribute to public health by improving prediabetes levels and also addressing the modifiable risk factors. An exercise protocol needs time to mitigate hyperglycemia in prediabetic individuals and to help provide information at community level.
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Affiliation(s)
- Sana Hafeez
- Faculty of Rehabilitation and Allied Health Sciences, Riphah International University, Lahore, 54000, Pakistan
- Department of Physical Therapy and Rehabilitation Sciences, University of Management and Technology, Lahore, 54000, Pakistan
| | - Syed Shakil-Ur-Rehman
- Faculty of Rehabilitation and Allied Health Sciences, Riphah International University, Lahore, 54000, Pakistan
| | - Saima Riaz
- Ayesha Bakht Institute of Medical Sciences, Lahore, 54000, Pakistan
| | - Sidra Hafeez
- Department of Obstetrics and Gynecology, Services Hospital, Lahore, 54000, Pakistan
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Wang G, Wang Y, Sheng K, Wang Y. Effect of probiotic extracellular vesicles and their applications on health and disease. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2025; 105:3539-3549. [PMID: 39806860 DOI: 10.1002/jsfa.14123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 07/25/2024] [Accepted: 12/31/2024] [Indexed: 01/16/2025]
Abstract
Probiotics have been established to exert a positive impact on the treatment of various diseases. Indeed, these active microorganisms have garnered significant attention in recent years for their potential to prevent and treat illnesses. Their beneficial effects have been hypothesized to be linked to their released extracellular vesicles. These nanoscale structures, secreted during the growth and metabolism of probiotics, possess favorable biocompatibility and targeting properties, thereby promoting intercellular material transport and signaling. This article aimed to review the bioactive components and functions of these probiotics vesicles, highlighting their role in the treatment of various diseases and discussing their potential future applications. By exploring the mechanisms of probiotic extracellular vesicles in disease development, this review aimed to provide a theoretical reference for further research on their therapeutic potential. © 2025 Society of Chemical Industry.
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Affiliation(s)
- Guangzhao Wang
- School of Life Sciences, Anhui University, Hefei, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China
| | - Yang Wang
- School of Life Sciences, Anhui University, Hefei, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China
| | - Kangliang Sheng
- School of Life Sciences, Anhui University, Hefei, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China
| | - Yongzhong Wang
- School of Life Sciences, Anhui University, Hefei, China
- Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China
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Sindhwani R, Bora KS, Hazra S. The dual challenge of diabesity: pathophysiology, management, and future directions. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:4891-4912. [PMID: 39680103 DOI: 10.1007/s00210-024-03713-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 12/07/2024] [Indexed: 12/17/2024]
Abstract
Diabesity, the concurrent occurrence of obesity and type-2 diabetes mellitus (T2DM), represents a pressing global health challenge characterized by intricate pathophysiological mechanisms and a wide range of associated comorbidities. Central to its development are insulin resistance, metabolic syndrome, and chronic low-grade inflammation mediated by dysregulated adipokine secretion and systemic metabolic dysfunction. These mechanisms underpin the progression of diabesity and its complications, including cardiovascular disease and hypertension. Management strategies encompass lifestyle interventions focusing on tailored dietary modifications and structured physical activity, pharmacological treatments targeting both glycemic control and weight loss, and surgical interventions such as bariatric surgery, which have demonstrated efficacy in achieving durable outcomes. Clinical trials and meta-analyses underscore the comparative advantages of different treatment modalities in terms of efficacy, safety, and sustainability. Moreover, long-term follow-up studies emphasize the critical need for sustained multidisciplinary interventions to prevent relapse and enhance patient outcomes. Future advancements in management include exploring precision medicine approaches that integrate individual metabolic profiles, lifestyle factors, and emerging therapeutic innovations. A multidisciplinary approach combining advanced therapeutic strategies and patient-centered care remains pivotal for optimizing management and improving prognoses for individuals with diabesity. This review highlights the complex interplay between obesity and T2DM, offering comprehensive insights into their pathophysiology, clinical presentation, and management paradigms.
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Affiliation(s)
- Ritika Sindhwani
- University Institute of Pharma Sciences, Chandigarh University, Mohali, 140413, Punjab, India
| | - Kundan Singh Bora
- University Institute of Pharma Sciences, Chandigarh University, Mohali, 140413, Punjab, India.
| | - Subhajit Hazra
- University Institute of Pharma Sciences, Chandigarh University, Mohali, 140413, Punjab, India
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Douae B, Samir B, Meriam EA, Fatima-Zahra Y, Youssef A. Mercuric Chloride Aggravates Hyperglycemia-Induced Anxiety and Depressive-Like Behaviors in Type 2 Diabetic Rats: Breakdown of the Antioxidant Defense System. Biol Trace Elem Res 2025:10.1007/s12011-025-04640-y. [PMID: 40279082 DOI: 10.1007/s12011-025-04640-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 04/22/2025] [Indexed: 04/26/2025]
Abstract
Introduction Type 2 diabetes mellitus (T2DM) is a global health problem frequently associated with biochemical disturbance and also, with a range of mental health disorders including such as anxiety and depression. Whereas, mercury chloride (HgCl₂) is a common environmental pollutant, which is neurotoxic and induces oxidative stress, especially in metabolic disorders like diabetes. The purpose of this investigation is to evaluate the interaction between hyperglycemia-induced oxidative stress and HgCl₂ toxicity and to assess their far-reaching effect spotlighted on biochemical and behavioral disturbances. By analyzing key oxidative stress markers and anxiety- and depression-like behaviors. Experimental design was carried out as follow: control group, HgCl₂-treated group, diabetic group and diabetic HgCl₂-treated group. Type 2 diabetes was induced in a diabetic model via streptozotocin (STZ) and nicotinamide (NA) injections. For the HgCl₂-exposed groups, rats were administered 0.375 mg/kg/day of HgCl₂ orally for 45 consecutive days. Additionally, behavioral tests were performed to examine anxiety- and depression-like behaviors, and hematological, biochemical, oxidative stress markers were assessed to evaluate systemic and neurotoxic effects. The results showed significant increases in fasting blood glucose levels in diabetic and HgCl₂-treated diabetic groups compared to controls (p < 0.001). Body weight significantly decreased in all treated groups (p < 0.05), with the greatest reduction observed in the HgCl₂-treated diabetic group. Behavioral analysis revealed heightened anxiety and depression-like behaviors, particularly in the HgCl₂-treated diabetic group (p < 0.05). Biochemical assessments indicated significant disruptions in lipid profiles and hepatic and renal markers, with pronounced effects in HgCl₂-treated diabetic rats (p < 0.05). Oxidative stress markers demonstrated elevated malondialdehyde and nitric oxide levels in the liver, hippocampus, and prefrontal cortex, paired with diminished antioxidant defences, including catalase and superoxide dismutase activities (p < 0.05). These findings underscore the synergistic role of hyperglycemia and HgCl₂ exposure in amplifying oxidative damage and emotional disturbances, suggesting a critical interplay between metabolic and neurotoxic pathways.
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Affiliation(s)
- Benloughmari Douae
- Laboratory of Biology and Health, Biology Department, Ibn Tofail University, Faculty of Sciences, Kenitra, Morocco
| | - Bikri Samir
- Laboratory of Biology and Health, Biology Department, Ibn Tofail University, Faculty of Sciences, Kenitra, Morocco.
- Higher School of Technology, Ibn Tofail University, Kenitra, Morocco.
| | - El Aboubi Meriam
- Laboratory of Natural Resources and Sustainable Development, Biology Department, Ibn Tofail University, Faculty of Sciences, Kenitra, Morocco
| | - Yassif Fatima-Zahra
- Laboratory of Biology and Health, Biology Department, Ibn Tofail University, Faculty of Sciences, Kenitra, Morocco
| | - Aboussaleh Youssef
- Laboratory of Biology and Health, Biology Department, Ibn Tofail University, Faculty of Sciences, Kenitra, Morocco
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10
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Pang X, Bai S, Feng Z, Zhang Y, Hu B, Zhang Y. Proteomic Analysis of Retinas in a Rat Model of High-Fat Diet-Induced Type 2 Diabetes: Implications of Interventional Targets for Nonproliferative Diabetic Retinopathy. Drug Des Devel Ther 2025; 19:2979-2999. [PMID: 40260199 PMCID: PMC12011038 DOI: 10.2147/dddt.s501318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 02/25/2025] [Indexed: 04/23/2025] Open
Abstract
Purpose This study aimed to establish a high-fat diet (HFD)-induced rat model of type 2 diabetes mellitus (T2DM) and employed tandem mass tag (TMT) proteomics to search for novel interventional targets for nonproliferative diabetic retinopathy (NPDR). Patients and Methods Six-week-old male Sprague-Dawley rats were randomly divided into a T2DM group fed a HFD and a normal group (NOR group) fed normal chow. After 6 w, the T2DM group was confirmed to have impaired glucose tolerance and was intraperitoneally injected with a single small dose of streptozotocin (STZ, 30 mg/kg), and blood glucose levels were monitored. The HFD was maintained for another 6 w, and an Evans blue assay and a dark-adapted electroretinogram (ERG) were conducted. Rat retinas were collected for morphology analysis, TMT proteomics analysis, and Western blotting. The expression patterns of selected differentially expressed proteins (DEPs) were validated in rat retinas via Western blotting and in aqueous humor from NPDR patients via slot blotting. Results After the 12-w HFD and STZ injection, the rats presented typical symptoms of T2DM. The retinas of T2DM rats presented pathological features of NPDR, including compromised scotopic ERGs, thinning of retinal layers, increased apoptosis and vascular leakage in the retina. Proteomic analysis identified DEPs and revealed profound dyslipidemia in T2DM rat retinas. The significant upregulation of the FABP3, TINAGL1, and COL4A3 proteins was validated in the retinas of the rats by Western blotting and in the aqueous humor of the NPDR patients by slot blotting. Conclusion In a rat model of HFD-induced T2DM that is consistent with the natural history and pathological features of NPDR, proteomics and bioinformatics analyses identified FABP3, TINAGL1, and COL4A3 as the 3 key upregulated proteins in retinas for the first time. These findings are supported by technical and clinical validations and provide novel targets for NPDR intervention.
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Affiliation(s)
- Xueyi Pang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, People’s Republic of China
| | - Siqiong Bai
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, People’s Republic of China
| | - Zhinan Feng
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, People’s Republic of China
| | - Yumin Zhang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, People’s Republic of China
| | - Bojie Hu
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, People’s Republic of China
| | - Yan Zhang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, People’s Republic of China
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11
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Yang J, Zhang CZ, Wang JJ, Zhang J. Metabolic improvement effects of jejunoileal side-to-side anastomosis in patients with type 2 diabetes and the glucagon-like peptide-1 mechanism. World J Diabetes 2025; 16:103567. [PMID: 40236870 PMCID: PMC11947908 DOI: 10.4239/wjd.v16.i4.103567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 01/06/2025] [Accepted: 01/14/2025] [Indexed: 02/28/2025] Open
Abstract
Wang et al explored the metabolic improvement effects of jejunoileal side-to-side anastomosis in patients with type 2 diabetes mellitus (T2DM), focusing on its multitarget metabolic regulatory potential through enhanced secretion of glucagon-like peptide-1. This surgical procedure alters the direction of nutrient flow, activates distal ileal L cells, and increases endogenous glucagon-like peptide-1 levels, supporting glucose homeostasis, enhancing insulin sensitivity, regulating body weight, and improving cardiovascular health. This structural adjustment transforms the gastrointestinal tract into an active endocrine regulatory organ, providing a pathway for metabolic improvement in patients with T2DM and other complex metabolic disorders. Although this procedure demonstrates significant metabolic improvements within 3-6 months after surgery, integrating hormone level measurements, metabolic marker analysis, and long-term follow-up has become crucial for exploring the complex mechanisms of T2DM in the field of metabolic surgery and T2DM management. Multidisciplinary collaboration involving support from endocrinology, nutrition, and rehabilitation teams before and after surgery is becoming increasingly vital in the long-term management of patients with T2DM. This collaboration optimizes surgical outcomes and enhances metabolic management. Side-to-side anastomosis shows potential in the multitarget metabolic management of T2DM, providing an additional intervention option for patients with T2DM and metabolic disorders.
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Affiliation(s)
- Jian Yang
- Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People’s Hospital, Yichang 443000, Hubei Province, China
- Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang 443000, Hubei Province, China
- Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang 443000, Hubei Province, China
| | - Cheng-Zhi Zhang
- Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People’s Hospital, Yichang 443000, Hubei Province, China
- Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang 443000, Hubei Province, China
- Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang 443000, Hubei Province, China
- Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People’s Hospital, Yichang 443000, Hubei Province, China
| | - Jiao-Jiao Wang
- Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People’s Hospital, Yichang 443000, Hubei Province, China
- Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang 443000, Hubei Province, China
- Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang 443000, Hubei Province, China
- Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People’s Hospital, Yichang 443000, Hubei Province, China
| | - Jing Zhang
- Hubei Key Laboratory of Ischemic Cardiovascular Disease, Yichang 443000, Hubei Province, China
- Hubei Provincial Clinical Research Center for Ischemic Cardiovascular Disease, Yichang 443000, Hubei Province, China
- Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People’s Hospital, Yichang 443000, Hubei Province, China
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12
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López-García P, Tejero-Ojeda MM, Vaquero ME, Carrión-Vázquez M. Current amyloid inhibitors: Therapeutic applications and nanomaterial-based innovations. Prog Neurobiol 2025; 247:102734. [PMID: 40024279 DOI: 10.1016/j.pneurobio.2025.102734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 02/06/2025] [Accepted: 02/20/2025] [Indexed: 03/04/2025]
Abstract
Amyloid proteins have long been in the spotlight for being involved in many degenerative diseases including Alzheimer´s, Parkinson´s or type 2 diabetes, which currently cannot be prevented and for which there is no effective treatment or cure. Here we provide a comprehensive review of inhibitors that act directly on the amyloidogenic pathway (at the monomer, oligomer or fibril level) of key pathological amyloids, focusing on the most representative amyloid-related diseases. We discuss the latest advances in preclinical and clinical trials, focusing on cutting-edge developments, particularly on nanomaterials-based inhibitors, which offer unprecedented opportunities to address the complexity of protein misfolding disorders and are revolutionizing the landscape of anti-amyloid therapeutics. Notably, nanomaterials are impacting critical areas such as bioavailability, penetrability and functionality of compounds currently used in biomedicine, paving the way for more specific therapeutic solutions tailored to various amyloid-related diseases. Finally, we highlight the window of opportunity opened by comparative analysis with so-called functional amyloids for the development of innovative therapeutic approaches for these devastating diseases.
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13
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Ma J, Chen W, Vaishnani DK, Wang C, Xue S, Yang Q, Tong Y, Lei N, Zhao Z, Ying F. Curcumin Analog J7 Attenuates Liver Fibrosis and Metabolic Dysregulation in a Rat Model of Type 2 Diabetes via Modulation of TGF-β/Smad and NF-κB/BCL-2/BAX Pathways. Drug Des Devel Ther 2025; 19:2411-2432. [PMID: 40190815 PMCID: PMC11971964 DOI: 10.2147/dddt.s511372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 03/23/2025] [Indexed: 04/09/2025] Open
Abstract
Objective To evaluate the therapeutic potential of the curcumin analog J7 in protecting the liver and regulating glucose and lipid metabolism in rats with type 2 diabetes. Methods Bioinformatics methods were used to identify signaling pathways linked to diabetic liver disease. Diabetic rats were treated with curcumin, low-dose J7, or high-dose J7, and liver function and fibrosis were assessed through biochemical analyses, histopathology, immunohistochemistry, and ELISA. Results J7 administration significantly improved lisver function, reduced fibrosis, and regulated metabolic profiles in diabetic rats. J7 downregulated TGF-β1, NF-κB p65, and BAX, while upregulating BCL-2, showing superior effects to traditional curcumin in reducing TGF-β1 and inhibiting α-SMA expression. Conclusion J7 demonstrates potential as a therapeutic agent for managing liver complications in type 2 diabetes, effectively attenuating liver fibrosis and regulating metabolism through the modulation of key signaling pathways and proteins.
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Affiliation(s)
- Jun Ma
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China
| | - Wei Chen
- Renji College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China
| | - Deep K Vaishnani
- School of International Studies, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China
| | - Congying Wang
- Renji College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China
| | - Shuman Xue
- Renji College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China
| | - Qiuqin Yang
- School of Clinical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China
| | - Yuheng Tong
- School of Clinical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China
| | - Ningjia Lei
- Pharmacy College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China
| | - Zhichao Zhao
- Department of Critical Care Medicine, Yuyao People’s Hospital, Yuyao, Zhejiang, 315400, People’s Republic of China
| | - Furong Ying
- Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China
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14
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Aslam MW, Sabri S, Umar A, Khan MS, Abbas MY, Khan MU, Wajid M. Exploring the antibiotic potential of copper carbonate nanoparticles, wound healing, and glucose-lowering effects in diabetic albino mice. Biochem Biophys Res Commun 2025; 754:151527. [PMID: 40015075 DOI: 10.1016/j.bbrc.2025.151527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/17/2025] [Accepted: 02/21/2025] [Indexed: 03/01/2025]
Abstract
Bio-Nanoscience is an emerging field that integrates nanotechnology with biological systems to revolutionize medicine, agriculture, and environmental sustainability through innovative and targeted solutions. The aim of this study was to synthesize copper carbonate nanoparticles and to investigate their antibacterial, wound healing, and glucose-lowering properties. Nanoparticles (NPs) were Synthesized through chemical reduction method and confirmed by using SEM, XRD, and FTIR. Characterization revealed that the nanoparticles had an average size of 55 ± 16 nm, exhibited a crystalline structure, and were free of impurities. Antibacterial tests demonstrated enhanced inhibition zones for Pseudomonas spp., S. aureus, and other bacterial strains, with the largest zone of inhibition observed at 12 mg/ml, measuring 18.5 ± 1.05 mm for Pseudomonas spp. In wound healing activity in diabetic mice observations revealed a complete wound closure in NPs treated mice by day 14 as compared to the control group (96.10 % wound closure). Nanoparticle administration (oral) also significantly reduced glucose levels in diabetic mice after 15 days in the experimental period, whereas fasting glucose levels reduced from 398.00 ± 6.16 to 116.67 ± 12.47 mg/dl. The docking studies of copper carbonate nanoparticles (NPs) with proteins involved in wound healing, including Antileukoproteinase (-2.7 kcal/mol), Casein (-2.5 kcal/mol), Collagen (-2.9 kcal/mol), Lysozyme (-2.8 kcal/mol), and Phospholipase (-3.9 kcal/mol), revealed significant binding affinities, suggesting potential applications in enhancing wound healing processes. Therefore, the copper carbonate nanoparticles demonstrate strong antibacterial properties and show promising effects on wound healing, along with blood glucose-lowering activity. These findings suggest their potential in biomedical applications, particularly for treating diabetes and bacterial infections.
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Affiliation(s)
- Muhammad Waseem Aslam
- Department of Zoology, Faculty of Life Sciences, University of Okara, Okara, 56130, Pakistan
| | - Sabeen Sabri
- Department of Microbiology and Molecular Genetics, Faculty of Life Sciences, University of Okara, Okara, 56130, Pakistan
| | - Ali Umar
- Department of Zoology, Faculty of Life Sciences, University of Okara, Okara, 56130, Pakistan
| | - Muhammad Saleem Khan
- Department of Zoology, Faculty of Life Sciences, University of Okara, Okara, 56130, Pakistan.
| | - Muhammad Yasir Abbas
- Department of Zoology, Faculty of Life Sciences, University of Okara, Okara, 56130, Pakistan
| | | | - Muhammad Wajid
- Department of Zoology, Faculty of Life Sciences, University of Okara, Okara, 56130, Pakistan
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15
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Koerner R, Valente O, Tao A, Rechenberg K. Gratitude Interventions in Individuals With Diabetes: An Integrative Review. Holist Nurs Pract 2025:00004650-990000000-00081. [PMID: 40132090 DOI: 10.1097/hnp.0000000000000732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2025]
Abstract
Diabetes is a chronic, complex condition, which requires intensive daily management for adequate glycemic control. The burden of daily tasks necessary for diabetes self-management can negatively impact psychosocial outcomes. The practice of gratitude in patients with chronic conditions has demonstrated improvement in poor psychosocial outcomes. The purpose of this review is to examine the effect of gratitude interventions on glycemic and psychosocial outcomes in individuals with diabetes. We searched 5 databases in September 2024 to identify research articles that met inclusion criteria. Six studies met inclusion criteria. Interventions included gratitude journaling, gratitude therapy, writing a gratitude letter, and gratitude reflection. Results indicate gratitude is a feasible intervention and may improve anxiety and depressive symptoms, quality of life, and coping with diabetes. There was heterogeneity in intervention delivery and results. Further research is required to ascertain the extent of correlation between gratitude, and glycemic and psychosocial outcomes.
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Affiliation(s)
- Rebecca Koerner
- Author Affiliation: College of Nursing, University of South Florida, Tampa, Florida
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16
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Caturano A, Erul E, Nilo R, Nilo D, Russo V, Rinaldi L, Acierno C, Gemelli M, Ricotta R, Sasso FC, Giordano A, Conte C, Ürün Y. Insulin resistance and cancer: molecular links and clinical perspectives. Mol Cell Biochem 2025:10.1007/s11010-025-05245-8. [PMID: 40089612 DOI: 10.1007/s11010-025-05245-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 02/23/2025] [Indexed: 03/17/2025]
Abstract
The association between insulin resistance (IR), type 2 diabetes mellitus (T2DM), and cancer is increasingly recognized and poses an escalating global health challenge, as the incidence of these conditions continues to rise. Studies indicate that individuals with T2DM have a 10-20% increased risk of developing various solid tumors, including colorectal, breast, pancreatic, and liver cancers. The relative risk (RR) varies depending on cancer type, with pancreatic and liver cancers showing a particularly strong association (RR 2.0-2.5), while colorectal and breast cancers demonstrate a moderate increase (RR 1.2-1.5). Understanding these epidemiological trends is crucial for developing integrated management strategies. Given the global rise in T2DM and cancer cases, exploring the complex relationship between these conditions is critical. IR contributes to hyperglycemia, chronic inflammation, and altered lipid metabolism. Together, these factors create a pro-tumorigenic environment conducive to cancer development and progression. In individuals with IR, hyperinsulinemia triggers the insulin-insulin-like growth factor (IGF1R) signaling pathway, activating cancer-associated pathways such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PIK3CA), which promote cell proliferation and survival, thereby supporting tumor growth. Both IR and T2DM are linked to increased morbidity and mortality in patients with cancer. By providing an in-depth analysis of the molecular links between insulin resistance and cancer, this review offers valuable insights into the role of metabolic dysfunction in tumor progression. Addressing insulin resistance as a co-morbidity may open new avenues for risk assessment, early intervention, and the development of integrated treatment strategies to improve patient outcomes.
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Affiliation(s)
- Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138, Naples, Italy
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166, Rome, Italy
| | - Enes Erul
- Department of Medical Oncology, Faculty of Medicine, Ankara University, Ankara, 06620, Turkey
| | - Roberto Nilo
- Data Collection G-STeP Research Core Facility, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy
| | - Davide Nilo
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138, Naples, Italy
| | - Vincenzo Russo
- Department of Biology, College of Science and Technology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, 19122, USA
- Division of Cardiology, Department of Medical Translational Sciences, University of Campania Luigi Vanvitelli, 80138, Naples, Italy
| | - Luca Rinaldi
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, 86100, Campobasso, Italy
| | - Carlo Acierno
- Azienda Ospedaliera Regionale San Carlo, 85100, Potenza, Italy
| | - Maria Gemelli
- Medical Oncology Unit, IRCCS MultiMedica, Milan, Italy
| | | | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138, Naples, Italy
| | - Antonio Giordano
- Department of Biology, College of Science and Technology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA, 19122, USA
| | - Caterina Conte
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166, Rome, Italy
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, 20099, Milan, Italy
| | - Yüksel Ürün
- Department of Medical Oncology, Faculty of Medicine, Ankara University, Ankara, 06620, Turkey.
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Venuti MT, Roda E, Brandalise F, Sarkar M, Cappelletti M, Speciani AF, Soffientini I, Priori EC, Giammello F, Ratto D, Locatelli CA, Rossi P. A pathophysiological intersection between metabolic biomarkers and memory: a longitudinal study in the STZ-induced diabetic mouse model. Front Physiol 2025; 16:1455434. [PMID: 40144552 PMCID: PMC11937145 DOI: 10.3389/fphys.2025.1455434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 02/06/2025] [Indexed: 03/28/2025] Open
Abstract
Diabetes mellitus (DM) is a metabolic disorder characterized by high blood sugar levels due to insufficient insulin production or insulin resistance. Recently, metabolic biomarkers, such as glycated albumin (GA) and methylglyoxal (MGO), have been successfully employed for the management of diabetes and its complications. The main goal of this study was to investigate the relationship between metabolic parameters, related to diabetic conditions, and the recognition memory, a declarative episodic long-term memory, in a streptozotocin (STZ)-induced diabetes mouse model. The longitudinal experimental plan scheduled five experimental timepoints, starting from 9 months and lasting until 19 months of age, and included different evaluations: i) fasting serum glucose, GA, and MGO, ii) recognition memory performance; iii) histological examinations of pancreas and hippocampus. At 13 months of age, mice were randomly divided into two groups, and STZ (50 mg/kg i.p.) or vehicle was administered for 5 consecutive days. Mice were fed with a normal diet but, starting from 14 months, half of them were given water with a high sugar (HS) to explore the potential detrimental effects of HS intake to hyperglycemia. Our main outcomes are as follows: i) HS intake alone does not contribute to worsened diabetic condition/hyperglycemia; ii) GA emerges as a reliable biomarker for monitoring diabetic conditions, consistently increasing with hyperglycemia; iii) diabetic conditions correlate with a worsening of recognition memory; iv) diabetic mice display mild-to-severe insulitis and injured hippocampal cytoarchitecture, detectable in Ammon's horns regions CA1 and CA3; v) correlation among recovered normal fasting glycemic level and recognition memory, partial regaining of physiological pancreatic morphology, and hippocampal cytoarchitecture.
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Affiliation(s)
- Maria Teresa Venuti
- Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, Pavia, Italy
| | - Elisa Roda
- Laboratory of Clinical and Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Federico Brandalise
- Department of Biomedical Sciences, Div. Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy
| | - Meghma Sarkar
- Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, Pavia, Italy
| | | | | | - Irene Soffientini
- Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, Pavia, Italy
| | - Erica Cecilia Priori
- Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, Pavia, Italy
| | - Francesca Giammello
- Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, Pavia, Italy
| | - Daniela Ratto
- Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, Pavia, Italy
| | - Carlo A. Locatelli
- Laboratory of Clinical and Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Paola Rossi
- Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, Pavia, Italy
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Wang Y, Cai S, Wen W, Tan Y, Wang W, Xu J, Xiong P. A Network Pharmacology Study and In Vitro Evaluation of the Bioactive Compounds of Kadsura coccinea Leaf Extract for the Treatment of Type 2 Diabetes Mellitus. Molecules 2025; 30:1157. [PMID: 40076380 PMCID: PMC11901907 DOI: 10.3390/molecules30051157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 02/28/2025] [Accepted: 02/28/2025] [Indexed: 03/14/2025] Open
Abstract
Kadsura coccinea is a traditional Chinese medicine whose roots have long been used to treat various ailments, but little is known about the efficacy of its leaves. In this study, the antidiabetic activity of K. coccinea leaf extract (KCLE) was determined, the main components of KCLE were identified using UPLC-TOF-MS, and network pharmacology and molecular docking were integrated to elucidate the antidiabetic mechanism of KCLE. The results showed that KCLE effectively increased the glucose consumption of IR-HepG2 cells through pyruvate kinase (PK) and hexokinase (HK), promoted glycogen synthesis, and inhibited α-glucosidase and α-amylase activities. KCLE also improves diabetes by regulating AKT1, TNF, EGFR, and GSK3β. These targets (especially AKT1 and TNF) have a high binding affinity with the main active ingredients of KCLE (rutin, luteolin, demethylwedelolactone, maritimetin, and polydatin). Pathway enrichment analysis showed that the antidiabetic effect of KCLE was closely related to the PI3K-Akt signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, and FoxO signaling pathway. These findings provide a theoretical basis for promoting the pharmacodynamic development of K. coccinea and its application in treating diabetes.
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Affiliation(s)
| | | | | | | | | | | | - Ping Xiong
- Department of Pharmaceutical Engineering, South China Agricultural University, Guangzhou 510642, China
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19
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Rubino F, Cummings DE, Eckel RH, Cohen RV, Wilding JPH, Brown WA, Stanford FC, Batterham RL, Farooqi IS, Farpour-Lambert NJ, le Roux CW, Sattar N, Baur LA, Morrison KM, Misra A, Kadowaki T, Tham KW, Sumithran P, Garvey WT, Kirwan JP, Fernández-Real JM, Corkey BE, Toplak H, Kokkinos A, Kushner RF, Branca F, Valabhji J, Blüher M, Bornstein SR, Grill HJ, Ravussin E, Gregg E, Al Busaidi NB, Alfaris NF, Al Ozairi E, Carlsson LMS, Clément K, Després JP, Dixon JB, Galea G, Kaplan LM, Laferrère B, Laville M, Lim S, Luna Fuentes JR, Mooney VM, Nadglowski J, Urudinachi A, Olszanecka-Glinianowicz M, Pan A, Pattou F, Schauer PR, Tschöp MH, van der Merwe MT, Vettor R, Mingrone G. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol 2025; 13:221-262. [PMID: 39824205 PMCID: PMC11870235 DOI: 10.1016/s2213-8587(24)00316-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 09/15/2024] [Accepted: 10/07/2024] [Indexed: 01/20/2025]
Abstract
Current BMI-based measures of obesity can both underestimate and overestimate adiposity and provide inadequate information about health at the individual level, which undermines medically-sound approaches to health care and policy. This Commission sought to define clinical obesity as a condition of illness that, akin to the notion of chronic disease in other medical specialties, directly results from the effect of excess adiposity on the function of organs and tissues. The specific aim of the Commission was to establish objective criteria for disease diagnosis, aiding clinical decision making and prioritisation of therapeutic interventions and public health strategies. To this end, a group of 58 experts—representing multiple medical specialties and countries—discussed available evidence and participated in a consensus development process. Among these commissioners were people with lived experience of obesity to ensure consideration of patients’ perspectives. The Commission defines obesity as a condition characterised by excess adiposity, with or without abnormal distribution or function of adipose tissue, and with causes that are multifactorial and still incompletely understood. We define clinical obesity as a chronic, systemic illness characterised by alterations in the function of tissues, organs, the entire individual, or a combination thereof, due to excess adiposity. Clinical obesity can lead to severe end-organ damage, causing life-altering and potentially life-threatening complications (eg, heart attack, stroke, and renal failure). We define preclinical obesity as a state of excess adiposity with preserved function of other tissues and organs and a varying, but generally increased, risk of developing clinical obesity and several other non-communicable diseases (eg, type 2 diabetes, cardiovascular disease, certain types of cancer, and mental disorders). Although the risk of mortality and obesity-associated diseases can rise as a continuum across increasing levels of fat mass, we differentiate between preclinical and clinical obesity (ie, health vs illness) for clinical and policy-related purposes. We recommend that BMI should be used only as a surrogate measure of health risk at a population level, for epidemiological studies, or for screening purposes, rather than as an individual measure of health. Excess adiposity should be confirmed by either direct measurement of body fat, where available, or at least one anthropometric criterion (eg, waist circumference, waist-to-hip ratio, or waist-to-height ratio) in addition to BMI, using validated methods and cutoff points appropriate to age, gender, and ethnicity. In people with very high BMI (ie, >40 kg/m2), however, excess adiposity can pragmatically be assumed, and no further confirmation is required. We also recommend that people with confirmed obesity status (ie, excess adiposity with or without abnormal organ or tissue function) should be assessed for clinical obesity. The diagnosis of clinical obesity requires one or both of the following main criteria: evidence of reduced organ or tissue function due to obesity (ie, signs, symptoms, or diagnostic tests showing abnormalities in the function of one or more tissue or organ system); or substantial, age-adjusted limitations of daily activities reflecting the specific effect of obesity on mobility, other basic activities of daily living (eg, bathing, dressing, toileting, continence, and eating), or both. People with clinical obesity should receive timely, evidence-based treatment, with the aim to induce improvement (or remission, when possible) of clinical manifestations of obesity and prevent progression to end-organ damage. People with preclinical obesity should undergo evidence-based health counselling, monitoring of their health status over time, and, when applicable, appropriate intervention to reduce risk of developing clinical obesity and other obesity-related diseases, as appropriate for the level of individual health risk. Policy makers and health authorities should ensure adequate and equitable access to available evidence-based treatments for individuals with clinical obesity, as appropriate for people with a chronic and potentially life-threatening illness. Public health strategies to reduce the incidence and prevalence of obesity at population levels must be based on current scientific evidence, rather than unproven assumptions that blame individual responsibility for the development of obesity. Weight-based bias and stigma are major obstacles in efforts to effectively prevent and treat obesity; health-care professionals and policy makers should receive proper training to address this important issue of obesity. All recommendations presented in this Commission have been agreed with the highest level of consensus among the commissioners (grade of agreement 90–100%) and have been endorsed by 76 organisations worldwide, including scientific societies and patient advocacy groups.
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Affiliation(s)
- Francesco Rubino
- Metabolic and Bariatric Surgery, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK; King's College Hospital, London, UK.
| | - David E Cummings
- University of Washington, Seattle, WA, USA; Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
| | - Robert H Eckel
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Ricardo V Cohen
- Center for the Treatment of Obesity and Diabetes, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
| | - John P H Wilding
- Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK
| | - Wendy A Brown
- Monash University Department of Surgery, Central Clinical School, Alfred Health, Melbourne, VIC, Australia
| | - Fatima Cody Stanford
- Neuroendocrine Unit, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Endocrinology, Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Rachel L Batterham
- International Medical Affairs, Eli Lilly, Basingstoke, UK; Diabetes and Endocrinology, University College London, London, UK
| | - I Sadaf Farooqi
- Institute of Metabolic Science and National Institute for Health and Care Research, Cambridge Biomedical Research Centre at Addenbrookes Hospital, Cambridge, UK
| | - Nathalie J Farpour-Lambert
- Obesity Prevention and Care Program, Department of Medicine, University Hospitals of Geneva, Geneva, Switzerland
| | - Carel W le Roux
- Diabetes Complications Research Centre, University College Dublin, Dublin, Ireland
| | - Naveed Sattar
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
| | - Louise A Baur
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Weight Management Services, The Children's Hospital at Westmead, Sydney, NSW, Australia
| | - Katherine M Morrison
- Centre for Metabolism, Obesity and Diabetes Research, Department of Pediatrics, McMaster University, Hamilton, ON, Canada; McMaster Children's Hospital, Hamilton, ON, Canada
| | - Anoop Misra
- Fortis C-DOC Center of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India; National Diabetes Obesity and Cholesterol Foundation, New Delhi, India; Diabetes Foundation New Delhi, India
| | | | - Kwang Wei Tham
- Department of Endocrinology, Woodlands Health, National Healthcare Group, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Priya Sumithran
- Department of Surgery, School of Translational Medicine, Monash University, Melbourne, VIC, Australia; Department of Endocrinology and Diabetes, Alfred Health, Melbourne, VIC, Australia
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - John P Kirwan
- Pennington Biomedical Research Center, Baton Rouge, LA, USA
| | - José-Manuel Fernández-Real
- CIBER Pathophysiology of Obesity and Nutrition, Girona, Spain; Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain; Hospital Trueta of Girona and Institut d'Investigació Biomèdica de Girona, Girona, Spain
| | - Barbara E Corkey
- Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, USA
| | - Hermann Toplak
- Division of Endocrinology and Diabetology, Department of Medicine, University of Graz, Graz, Austria
| | - Alexander Kokkinos
- First Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Robert F Kushner
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Francesco Branca
- Department of Nutrition and Food Safety, World Health Organization, Geneva, Switzerland
| | - Jonathan Valabhji
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK; Department of Diabetes and Endocrinology, Chelsea and Westminster Hospital National Health Service Foundation Trust, London, UK
| | - Matthias Blüher
- Helmholtz Institute for Metabolic, Obesity and Vascular Research of Helmholtz Munich, University of Leipzig and University Hospital Leipzig, Leipzig, Germany
| | - Stefan R Bornstein
- Department of Internal Medicine III, Carl Gustav Carus University Hospital Dresden, Technical University Dresden, Dresden, Germany; School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Harvey J Grill
- Institute of Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA
| | - Eric Ravussin
- Pennington Biomedical Research Center, Baton Rouge, LA, USA
| | - Edward Gregg
- School of Population Health, Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Dublin, Ireland; School of Public Health, Imperial College London, London, UK
| | - Noor B Al Busaidi
- National Diabetes and Endocrine Center, Royal Hospital, Muscat, Oman; Oman Diabetes Association, Muscat, Oman
| | - Nasreen F Alfaris
- Obesity Endocrine and Metabolism Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Ebaa Al Ozairi
- Clinical Research Unit, Dasman Diabetes Institute, Dasman, Kuwait
| | - Lena M S Carlsson
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Karine Clément
- Nutrition and Obesities: Systemic Approaches, NutriOmics Research Group, INSERM, Sorbonne Université, Paris, France; Department of Nutrition, Pitié-Salpêtrière Hospital, Assistance Publique-Hospital of Paris, Paris, France
| | | | - John B Dixon
- Iverson Health Innovation Research institute, Swinburne University of Technology, Melbourne, VIC, Australia
| | - Gauden Galea
- Regional Office for Europe, World Health Organization, Geneva, Switzerland
| | - Lee M Kaplan
- Section on Obesity Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Blandine Laferrère
- Division of Endocrinology, Columbia University Irving Medical Center, New York, NY, USA
| | | | - Soo Lim
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seoul, South Korea
| | | | - Vicki M Mooney
- European Coalition for people Living with Obesity, Dublin, Ireland
| | | | - Agbo Urudinachi
- Department of Community Health, Alex Ekwueme Federal University Teaching Hospital Abakaliki, Abakaliki, Nigeria
| | - Magdalena Olszanecka-Glinianowicz
- Health Promotion and Obesity Management Unit, Department of Pathophysiology, Faculty of Medical Science, Medical University of Silesia, Katowice, Poland
| | - An Pan
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Francois Pattou
- Translational Research for Diabetes, Lille University, Lille University Hospital, Inserm, Institut Pasteur Lille, Lille, France; Department of General and Endocrine Surgery, Lille University Hospital, Lille, France
| | | | - Matthias H Tschöp
- Helmholtz Munich, Munich, Germany; Technical University of Munich, Munich, Germany
| | - Maria T van der Merwe
- University of Pretoria, Pretoria, South Africa; Nectare Waterfall City Hospital, Midrand, South Africa
| | - Roberto Vettor
- Internal Medicine, Center for the Study and the Integrated Treatment of Obesity, Department of Medicine, University of Padova, Padua, Italy; Center for Metabolic and Nutrition Related Diseases,Humanitas Research Hospital, Milan, Italy
| | - Geltrude Mingrone
- Division of Diabetes & Nutritional Sciences, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK; Catholic University of the Sacred Heart, Rome, Italy; University Polyclinic Foundation Agostino Gemelli IRCCS, Rome, Italy
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Biswas S, Mita MA, Islam S, Biswas S, Akhtar-E-Ekram M, Zaman S, Uddin MS, Saleh MA. Prospective role of lupeol from Pterocarpus santalinus leaf against diabetes: An in vitro, in silico, and in vivo investigation. Comput Biol Med 2025; 186:109680. [PMID: 39842236 DOI: 10.1016/j.compbiomed.2025.109680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 01/04/2025] [Accepted: 01/12/2025] [Indexed: 01/24/2025]
Abstract
Diabetes mellitus (DM) can be treated with various medications. However, individuals in underdeveloped countries may face challenges in using these treatments due to side effects and high costs. Anti-diabetic medications can inhibit enzymes, such as α-amylase, which is responsible for breaking down carbohydrates. In this investigation, 16 phytoconstituents were identified from Pterocarpus santalinus leaf extract through GC-MS analysis, and their significant antioxidant activities were noted. Among these, the pure compound lupeol demonstrated α-amylase inhibition activity of 86.13 ± 1.27 % (IC50 = 58.50 ± 0.83 μg/mL) in vitro. Additionally, lupeol showed the highest binding affinity in silico using PyRx and CB-Dock, with values of -9.5 and -9.3 kcal/mol, respectively. The in silico analysis also indicated that lupeol possesses acceptable ADMET properties, suggesting its potential as an anti-diabetic drug. A molecular dynamics simulation lasting 500 ns was conducted to evaluate hydrogen bonds, RMSF, RMSD, Rg, and SASA, confirming the stability and integrity of the docking scenarios. In STZ-induced diabetic mice, lupeol significantly reduced blood glucose levels by 70.82 % from day 0 to day 28. Furthermore, lupeol markedly decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while improving high-density lipoprotein cholesterol (HDL-C) levels in these mice. The antidiabetic effect of lupeol was further validated through histological examinations of the pancreas, heart, kidney, and liver of treated mice, alongside correlation analysis, CAP, and ANOSIM tests. Based on the findings from the in vitro, in silico, and in vivo investigations, this study concludes that lupeol may have potential anti-diabetic effects through the inhibition of the α-amylase enzyme.
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Affiliation(s)
- Suvro Biswas
- Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Mohasana Akter Mita
- Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Shirmin Islam
- Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Shovon Biswas
- Department of Industrial and Production Engineering, Bangladesh University of Engineering and Technology, Dhaka, 1000, Bangladesh
| | - Md Akhtar-E-Ekram
- Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Shahriar Zaman
- Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Md Salah Uddin
- Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh
| | - Md Abu Saleh
- Microbiology Laboratory, Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, 6205, Bangladesh.
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Li R, Tang Y, Huang W, Li R, Liu J. The Roles of Apolipoprotein A1-Binding Protein in Metabolic Diseases. Nutr Rev 2025:nuaf021. [PMID: 40036350 DOI: 10.1093/nutrit/nuaf021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2025] Open
Abstract
Metabolic disorders, including atherosclerosis, diabetes, and metabolic dysfunction-associated steatotic liver disease, are closely related to increased cardiovascular risks, significantly harming human life and health. Apolipoprotein A1-binding protein (AIBP), a multifunctional protein, plays crucial role in cholesterol metabolism. AIBP exerts an important action in managing metabolic diseases by interacting with apolipoprotein A-I and ATP-binding cassette transporter A1 activities to regulate high-density lipoprotein)-mediated cholesterol transport and to maintain lipid homeostasis. In addition, AIBP suppresses inflammatory stress and abnormal angiogenesis, and acts as an NAD(P)HX epimerase to optimize energy metabolism. In this review, the multiple roles of AIBP in clinical metabolic diseases are summarized, and AIBP is proposed to be a potential therapeutic target against metabolic diseases.
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Affiliation(s)
- Ruihan Li
- Key Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Education Department of Guangxi Zhuang Autonomous Region, Guilin Medical University, Guilin 541199, PR China
| | - Yuqi Tang
- Key Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Education Department of Guangxi Zhuang Autonomous Region, Guilin Medical University, Guilin 541199, PR China
| | - Wenjun Huang
- Key Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Education Department of Guangxi Zhuang Autonomous Region, Guilin Medical University, Guilin 541199, PR China
| | - Rong Li
- Key Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Education Department of Guangxi Zhuang Autonomous Region, Guilin Medical University, Guilin 541199, PR China
| | - Jiaqi Liu
- Key Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Education Department of Guangxi Zhuang Autonomous Region, Guilin Medical University, Guilin 541199, PR China
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Yarahmadi S, Nikkhoo B, Miraki P, Rahmani K. Investigating metabolic control and complications in type 2 diabetic patients with low income in northwest of Iran, 2023. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2025; 44:38. [PMID: 39940034 PMCID: PMC11823108 DOI: 10.1186/s41043-025-00742-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 01/06/2025] [Indexed: 02/14/2025]
Abstract
BACKGROUND AND AIM Socioeconomic factors are very important in non-communicable diseases (NCD) and their complications as a risk factor or as a barrier to receive effective health care. This study aimed to determine the prevalence of diabetes complications and factors related to glycemic control in type 2 diabetic patients with low income in Kurdistan Province, Iran. METHOD This cross-sectional study was conducted on 608 diabetic patients supported by the Imam Khomeini Relief Foundation in 2023 in the province of Kurdistan, northwest of Iran. In addition to collecting demographic data, major complications of diabetes were specified by clinical examination by specialist physicians and paraclinical data. Data analysis was performed in Stata version 16 using descriptive statistics and logistic regression modeling. RESULTS A total of 608, 76.6% female, with mean and standard deviation age 62.7 ± 9.7 years were investigated. Prevalence of retinopathy, nephropathy, neuropathy, and diabetic foot ulcers were 42.9%, 6.9%, 3.3% and 4.3%, respectively. HbA1C levels were favorable (≤ 7.5) in only 231 (38.0%) patients. Longer duration of diabetes was associated with worse glycemic control0.95 (OR = 0.95; 95%CI:0.90-0.96), whereas comorbidity of DM and hypertension (OR = 2.05; 1.36-3.10) was significantly associated with good glycemic control. CONCLUSION Based on the results obtained, the health care and glycemic control status of low-income diabetic patients is not favorable. Considering the vulnerability of this group due to their low-risk perception and low income, it is recommended to teach self-care behaviors and plan routine care to prevent disease complications and, if necessary, fully cover the cost of care for these patients by the national health system.
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Affiliation(s)
| | - Bahram Nikkhoo
- Department of Pathology, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Parya Miraki
- Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Khaled Rahmani
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
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23
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Lim EB, Cho YS. Identification of genetic loci enriched in obese or lean T2D cases in the Korean population. Genes Genomics 2025; 47:235-243. [PMID: 39693004 DOI: 10.1007/s13258-024-01602-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 11/26/2024] [Indexed: 12/19/2024]
Abstract
BACKGROUND Obesity causes many complex diseases including type 2 diabetes (T2D). Obesity increases the risk of T2D in Europeans, but there are many non-obese (lean) T2D patients in East Asia. OBJECTIVE To discover genetic factors enriched in obese or lean T2D patients, we conducted a genome-wide association (GWA) analysis for T2D stratified by BMI in the Korean population. METHODS In the discovery stage, 654 and 247 individuals classified as obese (BMI > 25) and lean (BMI < 23) T2D patients, respectively, were compared with 3,842 control subjects for GWA analysis. Several BMI-stratified T2D variants detected in the discovery stage were further tested in the replication stage, which included 402 obese and 220 lean T2D cases, and 3,615 controls. RESULTS Meta-analysis combining the discovery and replication stages detected two variants with genome-wide significance: rs2356138 [P = 2.8 × 10-8, OR = 2.06 (1.59-2.65)] in obese T2D subjects and rs9295478 [P = 2.5 × 10-9, OR = 1.61 (1.38-1.88)] in lean ones. The SNP rs9295478 is located in CDKAL1, a well-known T2D gene previously identified in several GWA studies. Meanwhile, the SNP rs2356138 is a previously unknown variant located in PKP4. CONCLUSION We discovered genetic loci enriched in obese or lean T2D patients in the Korean population. Our findings should facilitate more effective control of T2D in Koreans.
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Affiliation(s)
- Eun Bi Lim
- Department of Biomedical Science, Hallym University, Chuncheon, Gangwon State, 24252, Republic of Korea
| | - Yoon Shin Cho
- Department of Biomedical Science, Hallym University, Chuncheon, Gangwon State, 24252, Republic of Korea.
- Department of Neuroscience, Hallym University College of Medicine, Chuncheon, Gangwon State, 24252, Republic of Korea.
- GenoMax Co., Ltd, Humanities Building 2, 4314-4, Hallymdaehakgil 1, Chuncheon, Gangwon State, Republic of Korea.
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Singh A, Shadangi S, Gupta PK, Rana S. Type 2 Diabetes Mellitus: A Comprehensive Review of Pathophysiology, Comorbidities, and Emerging Therapies. Compr Physiol 2025; 15:e70003. [PMID: 39980164 DOI: 10.1002/cph4.70003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 02/03/2025] [Accepted: 02/07/2025] [Indexed: 02/22/2025]
Abstract
Humans are perhaps evolutionarily engineered to get deeply addicted to sugar, as it not only provides energy but also helps in storing fats, which helps in survival during starvation. Additionally, sugars (glucose and fructose) stimulate the feel-good factor, as they trigger the secretion of serotonin and dopamine in the brain, associated with the reward sensation, uplifting the mood in general. However, when consumed in excess, it contributes to energy imbalance, weight gain, and obesity, leading to the onset of a complex metabolic disorder, generally referred to as diabetes. Type 2 diabetes mellitus (T2DM) is one of the most prevalent forms of diabetes, nearly affecting all age groups. T2DM is clinically diagnosed with a cardinal sign of chronic hyperglycemia (excessive sugar in the blood). Chronic hyperglycemia, coupled with dysfunctions of pancreatic β-cells, insulin resistance, and immune inflammation, further exacerbate the pathology of T2DM. Uncontrolled T2DM, a major public health concern, also contributes significantly toward the onset and progression of several micro- and macrovascular diseases, such as diabetic retinopathy, nephropathy, neuropathy, atherosclerosis, and cardiovascular diseases, including cancer. The current review discusses the epidemiology, causative factors, pathophysiology, and associated comorbidities, including the existing and emerging therapies related to T2DM. It also provides a future roadmap for alternative drug discovery for the management of T2DM.
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Affiliation(s)
- Aditi Singh
- Chemical Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Odisha, India
| | - Sucharita Shadangi
- Chemical Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Odisha, India
| | - Pulkit Kr Gupta
- Chemical Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Odisha, India
| | - Soumendra Rana
- Chemical Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Odisha, India
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25
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Singh A, Ashraf S, Irfan H, Venjhraj F, Verma A, Shaukat A, Tariq MD, Hamza HM. Heart failure and microvascular dysfunction: an in-depth review of mechanisms, diagnostic strategies, and innovative therapies. Ann Med Surg (Lond) 2025; 87:616-626. [PMID: 40110322 PMCID: PMC11918592 DOI: 10.1097/ms9.0000000000002971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 01/10/2025] [Indexed: 03/22/2025] Open
Abstract
Microvascular dysfunction (MVD) is increasingly recognized as a critical contributor to the pathogenesis of heart failure (HF), particularly in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Coronary microvascular dysfunction (CMD) significantly impacts HFpEF by reducing coronary flow reserve and myocardial perfusion reserve, leading to adverse outcomes such as myocardial ischemia, diastolic dysfunction, and increased risk of major cardiovascular events, including atrial fibrillation. In HFrEF, microvascular impairment is linked to heightened oxidative stress, reduced nitric oxide production, and activation of the renin-angiotensin-aldosterone system, further driving disease progression and contributing to poor prognosis. Advancements in diagnostic techniques, such as positron emission tomography, cardiac magnetic resonance imaging, and biomarker analysis, improve our ability to assess CMD in heart failure patients, enabling earlier diagnosis and risk stratification. Emerging therapies, including sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, and endothelial-targeted interventions, enhance microvascular function and improve patient outcomes. The role of personalized medicine is becoming increasingly important, as individualized therapeutic approaches tailored to patient-specific microvascular abnormalities are essential for optimizing treatment effectiveness. This review underscores the pivotal role of MVD in HF. It highlights the urgent need for innovative therapeutic strategies and diagnostic tools to address this complex condition and improve clinical outcomes for HF patients.
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Affiliation(s)
- Ajeet Singh
- Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Saad Ashraf
- Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Hamza Irfan
- Department of Ophthalmology, Shaikh Khalifa Bin Zayed Al Nahyan Medical and Dental College, Lahore, Pakistan
| | - Fnu Venjhraj
- Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan
| | - Amogh Verma
- SR Sanjeevani Hospital, Kalyanpur, Siraha, Nepal
| | - Ayesha Shaukat
- Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
| | - Muhammad Daoud Tariq
- Department of Internal Medicine, Foundation University Medical College, Islamabad, Pakistan
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Al-Humaidi JY, Abouzied AS, Zaki ME, Abolibda TZ, Alruwaili AH, Albedair LA, Mukhrish YE, Gomha SM. Investigating the efficacy of naphthalene-thiazole hybrid hydrazones as α-glucosidase inhibitors. J Mol Struct 2025; 1322:140288. [DOI: 10.1016/j.molstruc.2024.140288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
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Graells T, Lin YT, Ahmad S, Fall T, Ärnlöv J. The urinary microbiome in association with diabetes and diabetic kidney disease: A systematic review. PLoS One 2025; 20:e0317960. [PMID: 39888908 PMCID: PMC11785297 DOI: 10.1371/journal.pone.0317960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 01/06/2025] [Indexed: 02/02/2025] Open
Abstract
BACKGROUND The urinary microbiome, or urobiome, is a novel area of research that has been gaining attention recently, as urine was thought to be sterile for years. There is limited information about the composition of the urobiome in health and disease. The urobiome may be affected by several factors and diseases such as diabetes, a disease that often leads to kidney damage. Thus, we need to understand the role of the urobiome to assess and monitor kidney disease related to diabetes over time. METHODS We conducted a systematic review to summarize knowledge about the urobiome in association with diabetes mellitus and diabetic kidney disease. The search was conducted in several electronic databases until November 2024. RESULTS Eighteen studies were selected including cross-sectional case-control studies, cross-sectional surveys and one prospective longitudinal study. In total, the urobiome of 1,571 people was sequenced, of which 662 people had diabetes, and of these 36 had confirmed diabetic kidney disease; 609 were healthy individuals, 179 had prediabetes or were at risk of type 2 diabetes mellitus and 121 did not have diabetes but had other comorbidities. Eight studies analysed data from females, one was focused on male data, and the other nine had mixed female-male data. Most of the studies had a small sample size, used voided midstream urine, and used 16S rRNA sequencing. CONCLUSION This systematic review summarizes trends seen throughout published data available to have a first baseline knowledge of the urinary microbiome, and its microbiota, in association with diabetes including the decreased richness and α-diversity in urinary microbiota in individuals with diabetes compared to healthy controls and the decreased α-diversity with the evolution of kidney disease independently of the cause.
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Affiliation(s)
- Tiscar Graells
- Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institute, Huddinge, Stockholm, Sweden
| | - Yi-Ting Lin
- Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institute, Huddinge, Stockholm, Sweden
- Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shafqat Ahmad
- Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
- Preventive Medicine Division, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America
- Natural Sciences, Technology and Environmental Studies, Södertörn University, Huddinge, Sweden
| | - Tove Fall
- Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Johan Ärnlöv
- Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institute, Huddinge, Stockholm, Sweden
- Center for Clinical Research Dalarna, Uppsala University, Falun, Sweden
- School of Health and Welfare, Dalarna University, Falun, Sweden
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Enejoh OA, Okonkwo CH, Nortey H, Kemiki OA, Moses A, Mbaoji FN, Yusuf AS, Awe OI. Machine learning and molecular dynamics simulations predict potential TGR5 agonists for type 2 diabetes treatment. Front Chem 2025; 12:1503593. [PMID: 39850718 PMCID: PMC11754275 DOI: 10.3389/fchem.2024.1503593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 12/13/2024] [Indexed: 01/25/2025] Open
Abstract
Introduction Treatment of type 2 diabetes (T2D) remains a significant challenge because of its multifactorial nature and complex metabolic pathways. There is growing interest in finding new therapeutic targets that could lead to safer and more effective treatment options. Takeda G protein-coupled receptor 5 (TGR5) is a promising antidiabetic target that plays a key role in metabolic regulation, especially in glucose homeostasis and energy expenditure. TGR5 agonists are attractive candidates for T2D therapy because of their ability to improve glycemic control. This study used machine learning-based models (ML), molecular docking (MD), and molecular dynamics simulations (MDS) to explore novel small molecules as potential TGR5 agonists. Methods Bioactivity data for known TGR5 agonists were obtained from the ChEMBL database. The dataset was cleaned and molecular descriptors based on Lipinski's rule of five were selected as input features for the ML model, which was built using the Random Forest algorithm. The optimized ML model was used to screen the COCONUT database and predict potential TGR5 agonists based on their molecular features. 6,656 compounds predicted from the COCONUT database were docked within the active site of TGR5 to calculate their binding energies. The four top-scoring compounds with the lowest binding energies were selected and their activities were compared to those of the co-crystallized ligand. A 100 ns MDS was used to assess the binding stability of the compounds to TGR5. Results Molecular docking results showed that the lead compounds had a stronger affinity for TGR5 than the cocrystallized ligand. MDS revealed that the lead compounds were stable within the TGR5 binding pocket. Discussion The combination of ML, MD, and MDS provides a powerful approach for predicting new TGR5 agonists that can be optimised for T2D treatment.
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Affiliation(s)
- Ojochenemi A. Enejoh
- Genetics, Genomics and Bioinformatics Department, National Biotechnology Research and Development Agency, Abuja, Nigeria
| | | | - Hector Nortey
- Department of Clinical Pathology, Noguchi Memorial Institute for Medical Research, College of Health Science, University of Ghana, Accra, Ghana
| | - Olalekan A. Kemiki
- Molecular and Tissue Culture Laboratory, Babcock University, Ilisan-remo, Ogun State, Nigeria
| | - Ainembabazi Moses
- African Centers of Excellence in Bioinformatics and data intensive sciences, Department of Immunology and Microbiology, Makerere University, Makerere, Uganda
- Infectious Disease Institute (IDI), Makerere University, Kampala, Uganda
| | - Florence N. Mbaoji
- Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu, Nigeria
| | - Abdulrazak S. Yusuf
- Department of Biochemistry, Faculty of Basic Health Science, Bayero University, Kano, Nigeria
| | - Olaitan I. Awe
- African Society for Bioinformatics and Computational Biology, Cape Town, South Africa
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Green C, Zaman V, Blumenstock K, Banik NL, Haque A. Dysregulation of Metabolic Peptides in the Gut-Brain Axis Promotes Hyperinsulinemia, Obesity, and Neurodegeneration. Biomedicines 2025; 13:132. [PMID: 39857716 PMCID: PMC11763097 DOI: 10.3390/biomedicines13010132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 12/31/2024] [Accepted: 01/05/2025] [Indexed: 01/27/2025] Open
Abstract
Metabolic peptides can influence metabolic processes and contribute to both inflammatory and/or anti-inflammatory responses. Studies have shown that there are thousands of metabolic peptides, made up of short chains of amino acids, that the human body produces. These peptides are crucial for regulating many different processes like metabolism and cell signaling, as they bind to receptors on various cells. This review will cover the role of three specific metabolic peptides and their roles in hyperinsulinemia, diabetes, inflammation, and neurodegeneration, as well as their roles in type 3 diabetes and dementia. The metabolic peptides glucagon-like peptide 1 (GLP-1), gastric inhibitor polypeptide (GIP), and pancreatic peptide (PP) will be discussed, as dysregulation within their processes can lead to the development of various inflammatory and neurodegenerative diseases. Research has been able to closely investigate the connections between these metabolic peptides and their links to the gut-brain axis, highlighting changes made in the gut that can lead to dysfunction in processes in the brain, as well as changes made in the brain that can lead to dysregulation in the gut. The role of metabolic peptides in the development and potentially reversal of diseases such as obesity, hyperinsulinemia, and type 2 diabetes will also be discussed. Furthermore, we review the potential links between these conditions and neuroinflammation and the development of neurodegenerative diseases like dementia, specifically Parkinson's disease and Alzheimer's disease.
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Affiliation(s)
- Camille Green
- Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA; (C.G.); (V.Z.); (N.L.B.)
| | - Vandana Zaman
- Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA; (C.G.); (V.Z.); (N.L.B.)
- Ralph H. Johnson Veterans Administration Medical Center, 109 Bee Street, Charleston, SC 29401, USA;
| | - Kayce Blumenstock
- Ralph H. Johnson Veterans Administration Medical Center, 109 Bee Street, Charleston, SC 29401, USA;
- Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
| | - Narendra L. Banik
- Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA; (C.G.); (V.Z.); (N.L.B.)
- Ralph H. Johnson Veterans Administration Medical Center, 109 Bee Street, Charleston, SC 29401, USA;
- Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
| | - Azizul Haque
- Department of Neurosurgery, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA; (C.G.); (V.Z.); (N.L.B.)
- Ralph H. Johnson Veterans Administration Medical Center, 109 Bee Street, Charleston, SC 29401, USA;
- Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
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Yeung D, Talukder A, Shi M, Umbach DM, Li Y, Motsinger-Reif A, Hwang JJ, Fan Z, Li L. Differences in brain spindle density during sleep between patients with and without type 2 diabetes. Comput Biol Med 2025; 184:109484. [PMID: 39622099 DOI: 10.1016/j.compbiomed.2024.109484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 11/15/2024] [Accepted: 11/25/2024] [Indexed: 12/22/2024]
Abstract
BACKGROUND Sleep spindles may be implicated in sensing and regulation of peripheral glucose. Whether spindle density in patients with type 2 diabetes mellitus (T2DM) differs from that of healthy subjects is unknown. METHODS Our retrospective analysis of polysomnography (PSG) studies identified 952 patients with T2DM and 952 sex-, age- and BMI-matched control subjects. We extracted spindles from PSG electroencephalograms and used rank-based statistical methods to test for differences between subjects with and without diabetes. We also explored potential modifiers of spindle density differences. We replicated our analysis on independent data from the Sleep Heart Health Study. RESULTS We found that patients with T2DM exhibited about half the spindle density during sleep as matched controls (P < 0.0001). The replication dataset showed similar trends. The patient-minus-control paired difference in spindle density for pairs where the patient had major complications were larger than corresponding paired differences in pairs where the patient lacked major complications, despite both patient groups having significantly lower spindle density compared to their respective control subjects. Patients with a prescription for a glucagon-like peptide 1 receptor agonist had significantly higher spindle density than those without one (P ≤ 0.03). Spindle density in patients with T2DM monotonically decreased as their highest recorded HbA1C level increased (P ≤ 0.003). CONCLUSIONS T2DM patients had significantly lower spindle density than control subjects; the size of that difference was correlated with markers of disease severity (complications and glycemic control). These findings expand our understanding of the relationships between sleep and glucose regulation.
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Affiliation(s)
- Deryck Yeung
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
| | - Amlan Talukder
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
| | - Min Shi
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
| | - David M Umbach
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
| | - Yuanyuan Li
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
| | - Alison Motsinger-Reif
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
| | - Janice J Hwang
- Division of Endocrinology and Metabolism and Department of Internal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Zheng Fan
- Division of Sleep Medicine and Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Leping Li
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
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Song J, Wu Y, Chen Y, Sun X, Zhang Z. Epigenetic regulatory mechanism of macrophage polarization in diabetic wound healing (Review). Mol Med Rep 2025; 31:2. [PMID: 39422035 PMCID: PMC11551531 DOI: 10.3892/mmr.2024.13367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 09/24/2024] [Indexed: 10/19/2024] Open
Abstract
Diabetic wounds represent a significant complication of diabetes and present a substantial challenge to global public health. Macrophages are crucial effector cells that play a pivotal role in the pathogenesis of diabetic wounds, through their polarization into distinct functional phenotypes. The field of epigenetics has emerged as a rapidly advancing research area, as this phenomenon has the potential to markedly affect gene expression, cellular differentiation, tissue development and susceptibility to disease. Understanding epigenetic mechanisms is crucial to further exploring disease pathogenesis. A growing body of scientific evidence has highlighted the pivotal role of epigenetics in the regulation of macrophage phenotypes. Various epigenetic mechanisms, such as DNA methylation, histone modification and non‑coding RNAs, are involved in the modulation of macrophage phenotype differentiation in response to the various environmental stimuli present in diabetic wounds. The present review provided an overview of the various changes that take place in macrophage phenotypes and functions within diabetic wounds and discussed the emerging role of epigenetic modifications in terms of regulating macrophage plasticity in diabetic wounds. It is hoped that this synthesis of information will facilitate the elucidation of diabetic wound pathogenesis and the identification of potential therapeutic targets.
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Affiliation(s)
- Jielin Song
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
| | - Yuqing Wu
- The First Clinical Medical College, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510000, P.R. China
| | - Yunli Chen
- The First Clinical Medical College, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510000, P.R. China
| | - Xu Sun
- Department of Traditional Chinese Medicine Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
| | - Zhaohui Zhang
- Department of Traditional Chinese Medicine Surgery, The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
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Lee SA, Kim S, Kim SY, Park JY, Jung HS, Chung SS, Park KS. In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors. Diabetes Metab J 2025; 49:150-159. [PMID: 39444334 PMCID: PMC11788547 DOI: 10.4093/dmj.2024.0174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 06/17/2024] [Indexed: 10/25/2024] Open
Abstract
Four soluble factors-putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102-were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45-55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.
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Affiliation(s)
- Seung-Ah Lee
- Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea
| | - Subin Kim
- Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Seog-Young Kim
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea
| | - Jong Yoen Park
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
| | - Hye Seung Jung
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Sung Soo Chung
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea
| | - Kyong Soo Park
- Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Azmat F, Naseer MS, Safdar M, Bishoyi AK, Islam F, Imran A, Kanwal N, Zahra DE, Kalia R, Zafar A. Role of functional foods in diabetes management. NUTRIRE 2024; 50:1. [DOI: 10.1186/s41110-024-00304-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/13/2024] [Indexed: 01/03/2025]
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Bai Z, Gholipourshahraki T, Shrestha M, Hjelholt A, Hu S, Kjolby M, Rohde PD, Sørensen P. Evaluation of Bayesian Linear Regression derived gene set test methods. BMC Genomics 2024; 25:1236. [PMID: 39716056 DOI: 10.1186/s12864-024-11026-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 11/08/2024] [Indexed: 12/25/2024] Open
Abstract
BACKGROUND Gene set tests can pinpoint genes and biological pathways that exert small to moderate effects on complex diseases like Type 2 Diabetes (T2D). By aggregating genetic markers based on biological information, these tests can enhance the statistical power needed to detect genetic associations. RESULTS Our goal was to develop a gene set test utilizing Bayesian Linear Regression (BLR) models, which account for both linkage disequilibrium (LD) and the complex genetic architectures intrinsic to diseases, thereby increasing the detection power of genetic associations. Through a series of simulation studies, we demonstrated how the efficacy of BLR derived gene set tests is influenced by several factors, including the proportion of causal markers, the size of gene sets, the percentage of genetic variance explained by the gene set, and the genetic architecture of the traits. By using KEGG pathways, eQTLs, and regulatory elements as different kinds of gene sets with T2D results, we also assessed the performance of gene set tests in explaining more about real phenotypes. CONCLUSIONS Comparing our method with other approaches, such as the gold standard MAGMA (Multi-marker Analysis of Genomic Annotation) approach, our BLR gene set test showed superior performance. Combining performance of our method in simulated and real phenotypes, this suggests that our BLR-based approach could more accurately identify genes and biological pathways underlying complex diseases.
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Affiliation(s)
- Zhonghao Bai
- Center for Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark.
| | | | - Merina Shrestha
- Center for Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark
| | - Astrid Hjelholt
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
- Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - Sile Hu
- Human Genetics Centre of Excellence, Novo Nordisk Research Centre Oxford, Oxford, UK
| | - Mads Kjolby
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
- Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - Palle Duun Rohde
- Genomic Medicine, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Peter Sørensen
- Center for Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark.
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Ahn J, Kim E, Lee JE, Kim K. Diabetes Education Program for Nursing Students: A Systematic Review and Meta-Analysis. Nurs Open 2024; 11:e70105. [PMID: 39611704 PMCID: PMC11605939 DOI: 10.1002/nop2.70105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 11/09/2024] [Accepted: 11/15/2024] [Indexed: 11/30/2024] Open
Abstract
AIM The purpose of this study was to summarise the current state of the science on diabetes mellitus education programs for nursing students. DESIGN A systematic review and meta-analysis. METHODS Eligible studies were identified by searching PubMed, EMBASE, CINAHL, and Cochrane Library databases. Randomised controlled trials and quasi-experimental studies, published in English between 2013 and 2022, that examined diabetes education programs for nursing students were considered in the review. The quality of the articles was evaluated using the Joanna Briggs Institute's Critical Appraisal Checklist. Key information such as authors, study focus, population, sample size, details of intervention and control group treatments, outcome variables, and main findings were extracted and summarised in a data extraction form for further analyses and syntheses. RESULTS The literature search identified 464 articles, from which 13 studies were evaluated in the systematic review. Most studies (n = 12, 92.3%) used technology-based teaching methods, such as high-fidelity simulations, mobile applications, and virtual reality simulations. Regarding the evaluation of diabetes education program effectiveness, the majority of studies showed significant improvements in knowledge (n = 8, 61.5%), followed by satisfaction with learning (n = 4, 30.8%), nursing skill performance (n = 3, 23.1%), and self-confidence (n = 3, 23.1%) in nursing students. In meta-analyses, technology-based teaching interventions, compared to traditional education, showed no statistically significant improvement in diabetes knowledge (standard mean difference 9.52, 95% CI [-0.18, 19.21], p = 0.05) and self-efficacy (standard mean difference 24.09, 95% CI [-10.75, 58.92], p = 0.18). Despite this, technology-based methods demonstrated favourable effects on knowledge and self-efficacy against traditional education. Findings highlight the importance of emerging technology-based diabetes education programs tailored for nursing students, crucial for enhancing positive educational outcomes. No Patient or Public Contribution.
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Affiliation(s)
- Jeong‐Ah Ahn
- College of Nursing and Research Institute of Nursing ScienceAjou UniversitySuwonSouth Korea
| | - Eun‐Mi Kim
- College of Nursing, Research Institute of Nursing SciencePusan National UniversityPusanSouth Korea
| | - Jung Eun Lee
- College of NursingUniversity of Rhode IslandKingstonRIUSA
| | - Kyoung‐A Kim
- College of NursingSuwon Women's UniversitySuwonSouth Korea
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Heyram K, Manikandan J, Prabhu D, Jeyakanthan J. Computational insights into marine natural products as potential antidiabetic agents targeting the SIK2 protein kinase domain. SAR AND QSAR IN ENVIRONMENTAL RESEARCH 2024; 35:1129-1154. [PMID: 39773122 DOI: 10.1080/1062936x.2024.2443844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025]
Abstract
Diabetes mellitus (DM) affects over 77 million adults in India, with cases expected to reach 134 million by 2045. Current treatments, including sulfonylureas and thiazolidinediones, are inadequate, underscoring the need for novel therapeutic strategies. This study investigates marine natural products (MNPs) as alternative therapeutic agents targeting SIK2, a key enzyme involved in DM. The structural stability of the predicted SIK2 model was validated using computational methods and subsequently employed for structure-based virtual screening (SBVS) of over 38,000 MNPs. This approach identified five promising candidates: CMNPD21753 and CMNPD13370 from the Comprehensive Marine Natural Product Database, MNPD10685 from the Marine Natural Products Database, and SWMDRR053 and SWMDRR052 from the Seaweed Metabolite Database. The identified compounds demonstrated docking scores ranging from -7.64 to -11.95 kcal/mol and MMGBSA binding scores between -33.29 and -68.29 kcal/mol, with favourable predicted pharmacokinetic and toxicity profiles. Molecular dynamics simulations (MDS) revealed stronger predicted binding affinity for these compounds compared to ARN-3236, a known SIK2 inhibitor. Principal component (PC)-based free energy landscape (FEL) analysis further supported the stable binding of these compounds to SIK2. These computational findings highlight the potential of these leads as novel SIK2 inhibitors, warranting future in vitro and in vivo validation.
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Affiliation(s)
- K Heyram
- Structural Biology and Biocomputing Lab, Department of Bioinformatics, Alagappa University, Karaikudi, India
| | - J Manikandan
- Structural Biology and Biocomputing Lab, Department of Bioinformatics, Alagappa University, Karaikudi, India
| | - D Prabhu
- Centre for Drug Discovery, Department of Biotechnology, Karpagam Academy of Higher Education, Coimbatore, India
| | - J Jeyakanthan
- Structural Biology and Biocomputing Lab, Department of Bioinformatics, Alagappa University, Karaikudi, India
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Di Stefano E, Hüttmann N, Dekker P, Tomassen MMM, Oliviero T, Fogliano V, Udenigwe CC. Solid-state fermentation of green lentils by Lactiplantibacillus plantarum leads to formation of distinct peptides that are absorbable and enhances DPP-IV inhibitory activity in an intestinal Caco-2 cell model. Food Funct 2024; 15:11220-11235. [PMID: 39450545 DOI: 10.1039/d4fo03326d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2024]
Abstract
Food-derived bioactive compounds mimicking the effects of incretin therapies offer promising opportunities for combination therapies with functional foods, where food matrix interactions, gastrointestinal enzyme activity, and in situ bioactivity should be key considerations. In this study, green lentils were solid-state fermented with Lactiplantibacillus plantarum ATCC8014, in vitro digested and exposed to brush border enzymes of a Caco-2 cell monolayer. Intestinal absorption of peptides and DPP-IV inhibitory activity were then investigated. LC-MS/MS profiles showed that peptides mainly originated from parental proteins of the vicilin, convicilin and legumin families. Fermentation led to the formation of more hydrophobic peptides when compared to the unfermented flour and up to 33.6% of them were transported to the basolateral side of a Caco-2 cell monolayer. Peptides with more than 22 amino acids and with a mass greater than 2000 Da were minimally transported. 73 peptides were uniquely identified in the basolateral fraction suggesting that they resulted from the activity of the brush border enzymes. The DPP-IV activity of Caco-2 cells grown as a polarized monolayer was decreased by 37.3% when exposed to in vitro digested 72 h-fermented lentil flour and 10% when exposed to the unfermented one. Inhibition of DPP-IV in the basolateral fluids was improved in a dose-dependent manner and reached 7.9% when 500 mg mL-1 of in vitro digested 72 h fermented lentil flour was used. Glucose absorption and uptake were minimally affected, suggesting that the previously observed hypoglycemic properties of lentils are likely due to activity on DPP-IV rather than on the inhibition of glucose absorption.
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Affiliation(s)
- Elisa Di Stefano
- Food Quality and Design Group, Wageningen University and Research, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands
- School of Nutrition Sciences, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada.
| | - Nico Hüttmann
- John L. Holmes Mass Spectrometry Facility, University of Ottawa, Ottawa, ON K1N 6N5, Canada
| | - Pieter Dekker
- Food Quality and Design Group, Wageningen University and Research, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands
| | - Monic M M Tomassen
- Wageningen Food & Biobased Research, PO Box 17, 6700AA, Wageningen, The Netherlands
| | - Teresa Oliviero
- Food Quality and Design Group, Wageningen University and Research, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands
| | - Vincenzo Fogliano
- Food Quality and Design Group, Wageningen University and Research, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands
| | - Chibuike C Udenigwe
- School of Nutrition Sciences, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada.
- Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, K1N 5E3, Canada
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Munsakul N, Manosroi W, Buranapin S. Predictors and Predictive Score of In-Hospital Mortality in Diabetic Ketoacidosis: A Retrospective Cohort Study. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1833. [PMID: 39597018 PMCID: PMC11596054 DOI: 10.3390/medicina60111833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 10/29/2024] [Accepted: 11/07/2024] [Indexed: 11/29/2024]
Abstract
Background and Objectives: Diabetic ketoacidosis (DKA) is a critical complication of diabetes mellitus (DM). The primary objective of this study was to identify relevant clinical and biochemical predictors and create a predictive score for in-hospital DKA mortality. Materials and Methods: A 6-year retrospective cohort study of adult patients diagnosed with DKA and admitted to Chiang Mai University Hospital, a tertiary care center in Chiang Mai, Thailand, from 1 January 2015 to 31 December 2021, was conducted. Baseline clinical data and laboratory investigations were collected. The primary outcome was in-hospital mortality. Multivariable logistic regression analysis, clustered by type of diabetes, was performed to identify significant predictors. A predictive risk score was created using significant predictive factors identified by multivariable analysis. The results were presented as odds ratios (ORs) and 95% confidence intervals (CIs), with a significant p-value set at <0.05. Results: Ninety-three patients diagnosed with DKA were included in the study. Ten patients died during admission. Significant predictors for in-hospital mortality of DKA included age > 55 years (OR 7.8, p = 0.007), female gender (OR 3.5, p < 0.001), anion gap > 30 mEq/L (OR 2.6, p = 0.003), hemoglobin levels < 10 g/dL (OR 16.9, p < 0.001), and the presence of cardiovascular disease (OR 1.3, p = 0.046). The predictive risk score ranged from 1 to 14 for low risk, and 14.5-23.5 for high risk of in-hospital mortality. The predictive performance of the scoring system was 0.82 based on the area under the curve, with a sensitivity of 73.8% and specificity of 96.4%. Conclusions: Multiple clinical and biochemical factors, along with a predictive risk score, could assist in predicting in-hospital mortality of DKA and serve as a guide for physicians to identify patients at high risk. Nevertheless, as the predictive score was internally validated with data from a single institution, external validation in diverse healthcare settings with larger datasets or prospective cohorts is crucial to confirm the model's generalizability and predictive accuracy.
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Affiliation(s)
- Neera Munsakul
- Internal Medicine Department, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand;
| | - Worapaka Manosroi
- Endocrine and Metabolism Unit, Internal Medicine Department, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Supawan Buranapin
- Endocrine and Metabolism Unit, Internal Medicine Department, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
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Zhao H, Yin R, Wang Y, Wang Z, Zhang L, Xu Y, Wang D, Wu J, Wei L, Yang L, Zhao D. Association between blood heavy metals and diabetic kidney disease among type 2 diabetic patients: a cross-sectional study. Sci Rep 2024; 14:26823. [PMID: 39500961 PMCID: PMC11538502 DOI: 10.1038/s41598-024-77996-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 10/28/2024] [Indexed: 11/08/2024] Open
Abstract
Studies on the correlation of exposure to metals with diabetic kidney disease (DKD) is scarce, especially concerning the impact of mixed metals on DKD. This study aimed to explore the association of blood heavy metals with DKD risk among type 2 diabetes mellitus (T2DM) patients. This cross-sectional study enrolled patients with T2DM in NHANES 2011-2020. ICP‒MS was applied to detect five metals, namely, Pb, Cd, Hg, Se and Mn, in blood. At the same time, the impacts of exposure to single and mixed metals on DKD were assessed using multivariable logistic regression, WQS, and BKMR models. The relationship was examined based on age, sex, BMI, hypertension, smoking status and PIR. Totally 2362 participants were enrolled for final analysis. Among them, 634 (26.84%) patients undergoing T2DM had DKD. Logistic regression indicated that, Pb (Q4: OR [95% CI]: 1.557 [1.175, 2.064]) was related to DKD when all covariates were adjusted. The WQS analysis, which was set in a positive directional mode, suggested that Pb was correlated positively with a higher incidence of DKD. In BKMR analysis, linear dose‒response curves were generated for Pb when fixing the other metals in the 50th percentile. In addition, exposure to mixed metals was significantly positively related to DKD. Subgroup analysis during logistic regression demonstrated that Pb was significantly and positively related to DKD in females, over 50 years, those with over 25 kg/m2, no hypertension, no smoking status and under PIR. Serum albumin (ALB) did not regulate the indirect impact of blood Pb on DKD risk. The results showed that the increased mixed metal concentration may lead to an increased DKD risk among patients with T2DM. Blood Pb is positively related to the DKD risk in diabetic patients, especially, in females, over 50 years, those with over 25 kg/m2, no hypertension, no smoking status and under PIR in T2DM patients. According to our observations, Pb absorption at least slightly influences DKD occurrence and progression. More studies are needed to validate the results in this work and illustrate the relevant biological mechanism.
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Affiliation(s)
- Hongling Zhao
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
| | - Ruili Yin
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
| | - Yan Wang
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
| | - Zihang Wang
- Clinical Medicine, Fujian Medical University Clinical Medicine, Fuzhou, China
| | - Lijie Zhang
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
| | - Yongsong Xu
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
| | - Di Wang
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
| | - Jianbo Wu
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
| | - Lingling Wei
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
| | - Longyan Yang
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital Capital Medical University, Beijing, China.
- Beijing Key Laboratory of Diabetes Research and Care, Beijing, China.
| | - Dong Zhao
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital Capital Medical University, Beijing, China.
- Beijing Key Laboratory of Diabetes Research and Care, Beijing, China.
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Vora H, Kaur P. Prediabetes and diabetes in India: An HbA1c based epidemiology study. Diabetes Res Clin Pract 2024; 217:111889. [PMID: 39414085 DOI: 10.1016/j.diabres.2024.111889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 09/26/2024] [Accepted: 10/08/2024] [Indexed: 10/18/2024]
Abstract
BACKGROUND The relentless rise in Type 2 diabetes mellitus (T2DM) and prediabetes presents a complex challenge to India's healthcare system. This study analyses the prevalence and trends of these conditions in adults across Indian states using laboratory data collected during 2023. METHODS HbA1c values from 19,66,449 samples from adults alongside demographic and geographic details were retrospectively analysed. Data were stratified by state, age, and gender and evaluated against national statistics parameters such as food consumption and socio-economic status. RESULTS Substantial regional variation was seen across the country where 22.25% of the tested population was considered having prediabetes, and 27.18% with diabetes. Odisha had the highest rates, while J&K reported the lowest. Gender-specific trends indicate an increase in prevalence of diabetes among males compared to females. Age-wise data stratification shows a significant burden of prediabetes and diabetes in the economically productive age groups. Correlations between disease prevalence and state-specific grain consumption were observed, suggesting dietary influences. CONCLUSIONS The reported prevalence of prediabetes and diabetes higher than previous studies highlights the importance of regular screening. The use of HbA1c for estimation as a long-term average blood sugar marker helps to identify previously undiagnosed diabetes. The correlation of prevalence with food production underscores the importance of diet in disease management.
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Affiliation(s)
- Hardeep Vora
- Lead, Business Development and Technology Alliances, Thyrocare Technologies Ltd., Navi Mumbai, India.
| | - Preet Kaur
- Vice President, Lab Operations and Quality, Thyrocare Technologies Ltd., Navi Mumbai, India
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Gelsey FT, Schapiro D, Kosa K, Vass C, Perez-Nieves M, Pierce A, Poon JL, DiBenedetti D, Mansfield C. Perspectives and Preferences of People with Type 2 Diabetes for the Attributes of Weekly Insulin. Diabetes Ther 2024; 15:2367-2379. [PMID: 39347898 PMCID: PMC11467135 DOI: 10.1007/s13300-024-01652-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 09/03/2024] [Indexed: 10/01/2024] Open
Abstract
INTRODUCTION Daily insulin administration can be burdensome for people with type 2 diabetes (PwT2D) and can impact treatment adherence. This study investigated preferences for once-weekly, long-acting basal insulin for treatment of PwT2D. METHODS An online discrete-choice experiment was administered to PwT2D in the USA. Qualitative interviews informed the selection of six attributes: reduction in A1c level after 6 months, amount of time spent in optimal blood sugar range each day, number of serious low blood sugar events, number of nighttime low blood sugar events, change in weight because of the insulin over 6 months, and frequency of administration. Each participant completed eight questions offering a choice between two long-acting insulins; questions varied according to an experimental design. A fixed treatment choice question asked about preferences for daily versus weekly insulin, holding other treatment features constant. Data were analyzed using random-parameters logit models, and heterogeneity was explored through subgroup analyses. RESULTS Four hundred sixty-six PwT2D completed the survey (mean age, 57; mean A1c, 7.5%; 59.0% female); 33.3% of these were currently on a basal/bolus regimen, 34.3% used basal only, and 32.4% were insulin naive. Respondents placed the most importance on avoiding a 10-pound weight change and equal importance on the largest change in the number of serious and nighttime low blood sugar events per year and achieving the longest time in range included in the choice questions. There was significant heterogeneity in preferences by experience: insulin-naive respondents had stronger preferences for scheduled and flexible weekly insulin over daily insulin; 67.6% preferred flexible weekly over daily insulin, all else being equal. CONCLUSION PwT2D valued insulin efficacy and reducing treatment-related adverse events, with heterogeneity in the relative importance of administration frequency. All else being equal, respondents preferred weekly over daily basal insulin. These findings provide insights into the preferences of PwT2D considering weekly long-acting insulin.
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Affiliation(s)
| | | | | | | | | | - Anna Pierce
- RTI Health Solutions, Research Triangle Park, NC, USA
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Wang Y, Yan F, Chen Q, Liu F, Xu B, Liu Y, Huo G, Xu J, Li B, Wang S. High-fat diet promotes type 2 diabetes mellitus by disrupting gut microbial rhythms and short-chain fatty acid synthesis. Food Funct 2024; 15:10838-10852. [PMID: 39405046 DOI: 10.1039/d4fo02957g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/29/2024]
Abstract
Diabetes ranks among the top 10 causes of death globally, with over 90% of individuals diagnosed with diabetes having type 2 diabetes mellitus (T2DM). It is acknowledged that a high-fat diet (HFD) poses a serious risk for T2DM. The imbalance of intestinal flora, mediated by HFD, can potentially exacerbate the onset and progression of T2DM. However, the impact of HFD on pathological indicators and the intestinal microbiome in the development of T2DM has not been systematically investigated. Therefore, a HFD mouse model and a T2DM mouse model were established, respectively, in this study. The role of HFD as a driving factor in the development of T2DM was assessed using various measures, including basic pathological indicators of T2DM, lipid metabolism, liver oxidative stress, intestinal permeability, levels of inflammatory factors, gut microbiota, and short-chain fatty acids (SCFAs). The findings indicated that HFD could influence the aforementioned measures to align with T2DM changes, but the contribution of HFD varied across different pathological metrics of T2DM. The impact of HFD on low-density lipoprotein cholesterol, glutathione peroxidase, malondialdehyde, and tumor necrosis factor-α did not show a statistically significant difference from those observed in T2DM during its development. In addition, regarding gut microbes, HFD primarily influenced the alterations in bacteria capable of synthesizing SCFAs. The notable decrease in SCFA content in both serum and cecal matter further underscored the effect of HFD on SCFA-synthesising bacteria in mice. Hence, this research provided a systematic assessment of HFD's propelling role in T2DM's progression. It was inferred that gut microbes, particularly those capable of synthesizing SCFAs, could serve as potential targets for the future prevention and treatment of T2DM instigated by HFD.
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Affiliation(s)
- Yangrui Wang
- Food College, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China.
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China
| | - Fenfen Yan
- Food College, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China.
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China
- School of Food and Biology Engineering, Xuzhou University of Technology, Xuzhou, Jiangsu, 221018, China
| | - Qingxue Chen
- Food College, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China.
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China
| | - Fei Liu
- Food College, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China.
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China
| | - Baofeng Xu
- Food College, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China.
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China
| | - Yuanyuan Liu
- Food College, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China.
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China
| | - Guicheng Huo
- Food College, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China.
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China
| | - Jinsheng Xu
- Shanghai Binhan International Trade Co., Ltd, Shanghai, 200000, China
| | - Bailiang Li
- Food College, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China.
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China
| | - Song Wang
- Food College, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China.
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, Heilongjiang, 150030, China
- Shandong Yuwang Ecological Food Industry Co., Ltd, Dezhou, Shandong, 251200, China
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Pramanik R, Dey A, Chakrabarty AK, Banerjee D, Narwaria A, Sharma S, Rai RK, Katiyar CK, Dubey SK. Diabetes mellitus and Alzheimer's disease: Understanding disease mechanisms, their correlation, and promising dual activity of selected herbs. JOURNAL OF ETHNOPHARMACOLOGY 2024; 333:118402. [PMID: 38821139 DOI: 10.1016/j.jep.2024.118402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 05/12/2024] [Accepted: 05/27/2024] [Indexed: 06/02/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE This review explores the link between Type 2 Diabetes Mellitus (T2DM) and diabetes-induced Alzheimer's disease (AD). It emphasizes the shared pathophysiological links and mechanisms between the two conditions, focusing on reduced insulin levels and receptors, impaired glucose metabolism, insulin resistance, mitochondrial dysfunction, and oxidative damage in AD-affected brains-paralleling aspects of T2DM. The review suggests AD as a "diabetes of the brain," supported by cognitive enhancement through antidiabetic interventions. It focuses on the traditionally used Indian herbs as a means to manage both conditions while addressing developmental challenges. AIM OF THE STUDY This study explores the DM-AD connection, reviewing medicinal herbs with protective potential for both ailments, considering traditional uses and developmental challenges. MATERIALS AND METHODS Studied research, reviews, and ethnobotanical and scientific data from electronic databases and traditional books. RESULTS The study analyzes the pathophysiological links between DM and AD, emphasizing their interconnected factors. Eight Ayurvedic plants with dual protective effects against T2DM and AD are thoroughly reviewed with preclinical/clinical evidence. Historical context, phytoconstituents, and traditional applications are explored. Innovative formulations using these plants are examined. Challenges stemming from phytoconstituents' physicochemical properties are highlighted, prompting novel formulation development, including nanotechnology-based delivery systems. The study uncovers obstacles in formulating treatments for these diseases. CONCLUSION The review showcases the dual potential of chosen medicinal herbs against both diseases, along with their traditional applications, endorsing their use. It addresses formulation obstacles, proposing innovative delivery technologies for herbal therapies, while acknowledging their constraints. The review suggests the need for heightened investment and research in this area.
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Affiliation(s)
- Rima Pramanik
- R&D Healthcare Division, Emami Ltd, 13, BT Road, Belgharia, Kolkata, 700056, India
| | - Anuradha Dey
- R&D Healthcare Division, Emami Ltd, 13, BT Road, Belgharia, Kolkata, 700056, India
| | | | - Dipankar Banerjee
- R&D Healthcare Division, Emami Ltd, 13, BT Road, Belgharia, Kolkata, 700056, India
| | - Avinash Narwaria
- R&D Healthcare Division, Emami Ltd, 13, BT Road, Belgharia, Kolkata, 700056, India
| | - Swapnil Sharma
- Department of Pharmacy, Banasthali Vidyapith, Banasthali, 304022, Rajasthan, India
| | - Rajiva Kumar Rai
- R&D Healthcare Division, Emami Ltd, 13, BT Road, Belgharia, Kolkata, 700056, India
| | - Chandra Kant Katiyar
- R&D Healthcare Division, Emami Ltd, 13, BT Road, Belgharia, Kolkata, 700056, India
| | - Sunil Kumar Dubey
- R&D Healthcare Division, Emami Ltd, 13, BT Road, Belgharia, Kolkata, 700056, India.
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Hernández-Martín M, Garcimartín A, Bocanegra A, Macho-González A, García-Fernández RA, de Pascual-Teresa S, Redondo-Castillejo R, Bastida S, Sánchez-Muniz FJ, Benedí J, López-Oliva ME. Silicon-Enriched Meat Ameliorates Diabetic Dyslipidemia by Improving Cholesterol, Bile Acid Metabolism and Ileal Barrier Integrity in Rats with Late-Stage Type 2 Diabetes. Int J Mol Sci 2024; 25:11405. [PMID: 39518958 PMCID: PMC11547133 DOI: 10.3390/ijms252111405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 10/07/2024] [Accepted: 10/11/2024] [Indexed: 11/16/2024] Open
Abstract
Silicon as a functional ingredient of restructured meat (RM) shows antidiabetic and hypocholesterolemic effects in a type 2 diabetes mellitus (T2DM) rat model. The present paper investigated the mechanisms involved in this cholesterol-lowering effect by studying the impact of silicon-RM consumption on bile acid (BA) and cholesterol metabolism. In addition, the main effects of cecal BA and short-chain fatty acids derived from the microbiota on intestinal barrier integrity were also tested. Rats were fed an RM high-saturated-fat, high-cholesterol diet (HSFHCD) combined with a low dose of streptozotocin plus nicotinamide injection (LD group) and for an 8 wk. period. Silicon-RM was included in the HSFHCD as a functional food (LD-Si group). An early-stage T2DM group fed a high-saturated-fat diet (ED group) was used as a reference. Silicon decreased the BA pool with a higher hydrophilic BA profile and a lower ability to digest fat and decreased the damaging effects, increasing the occludin levels and the integrity of the intestinal barrier. The ileal BA uptake and hepatic BA synthesis through CYP7A1 were reduced by FXR/FGF15 signaling activation. The silicon up-regulated the hepatic and ileal FXR and LXRα/β, improving transintestinal cholesterol (TICE), biliary BA and cholesterol effluxes. The inclusion of silicon in meat products could be used as a new therapeutic nutritional tool in the treatment of diabetic dyslipidemia.
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Affiliation(s)
- Marina Hernández-Martín
- Departmental Section of Physiology, Pharmacy School, Complutense University of Madrid, 28040 Madrid, Spain;
- AFUSAN Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), 28040 Madrid, Spain; (A.G.); (A.B.); (A.M.-G.); (R.R.-C.); (S.B.); (F.J.S.-M.); (J.B.)
| | - Alba Garcimartín
- AFUSAN Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), 28040 Madrid, Spain; (A.G.); (A.B.); (A.M.-G.); (R.R.-C.); (S.B.); (F.J.S.-M.); (J.B.)
- Pharmacology, Pharmacognosy and Botany Department, Pharmacy School, Complutense University of Madrid, 28040 Madrid, Spain
| | - Aránzazu Bocanegra
- AFUSAN Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), 28040 Madrid, Spain; (A.G.); (A.B.); (A.M.-G.); (R.R.-C.); (S.B.); (F.J.S.-M.); (J.B.)
- Pharmacology, Pharmacognosy and Botany Department, Pharmacy School, Complutense University of Madrid, 28040 Madrid, Spain
| | - Adrián Macho-González
- AFUSAN Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), 28040 Madrid, Spain; (A.G.); (A.B.); (A.M.-G.); (R.R.-C.); (S.B.); (F.J.S.-M.); (J.B.)
- Nutrition and Food Science Department, Pharmacy School, Complutense University of Madrid, 28040 Madrid, Spain
| | - Rosa A. García-Fernández
- Animal Medicine and Surgery Department, Veterinary School, Complutense University of Madrid, 28040 Madrid, Spain;
| | - Sonia de Pascual-Teresa
- Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), 28040 Madrid, Spain;
| | - Rocío Redondo-Castillejo
- AFUSAN Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), 28040 Madrid, Spain; (A.G.); (A.B.); (A.M.-G.); (R.R.-C.); (S.B.); (F.J.S.-M.); (J.B.)
- Pharmacology, Pharmacognosy and Botany Department, Pharmacy School, Complutense University of Madrid, 28040 Madrid, Spain
| | - Sara Bastida
- AFUSAN Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), 28040 Madrid, Spain; (A.G.); (A.B.); (A.M.-G.); (R.R.-C.); (S.B.); (F.J.S.-M.); (J.B.)
- Nutrition and Food Science Department, Pharmacy School, Complutense University of Madrid, 28040 Madrid, Spain
| | - Francisco J. Sánchez-Muniz
- AFUSAN Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), 28040 Madrid, Spain; (A.G.); (A.B.); (A.M.-G.); (R.R.-C.); (S.B.); (F.J.S.-M.); (J.B.)
- Nutrition and Food Science Department, Pharmacy School, Complutense University of Madrid, 28040 Madrid, Spain
| | - Juana Benedí
- AFUSAN Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), 28040 Madrid, Spain; (A.G.); (A.B.); (A.M.-G.); (R.R.-C.); (S.B.); (F.J.S.-M.); (J.B.)
- Pharmacology, Pharmacognosy and Botany Department, Pharmacy School, Complutense University of Madrid, 28040 Madrid, Spain
| | - Mª Elvira López-Oliva
- Departmental Section of Physiology, Pharmacy School, Complutense University of Madrid, 28040 Madrid, Spain;
- AFUSAN Research Group, Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC), 28040 Madrid, Spain; (A.G.); (A.B.); (A.M.-G.); (R.R.-C.); (S.B.); (F.J.S.-M.); (J.B.)
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Nxumalo MB, Ntanzi N, Kumalo HM, Khan RB. Mitigating Hyperglycaemic Oxidative Stress in HepG2 Cells: The Role of Carica papaya Leaf and Root Extracts in Promoting Glucose Uptake and Antioxidant Defence. Nutrients 2024; 16:3496. [PMID: 39458491 PMCID: PMC11510471 DOI: 10.3390/nu16203496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 09/30/2024] [Accepted: 10/03/2024] [Indexed: 10/28/2024] Open
Abstract
Background/Objectives: Diabetes often goes undiagnosed, with 60% of people in Africa unaware of their condition. Type 2 diabetes mellitus (T2DM) is associated with insulin resistance and is treated with metformin, despite the undesirable side effects. Medicinal plants with therapeutic potential, such as Carica papaya, have shown promising anti-diabetic properties. This study explored the role of C. papaya leaf and root extracts compared to metformin in reducing hyperglycaemia-induced oxidative stress and their impact on liver function using HepG2 as a reference. Methods: The cytotoxicity was assessed through the MTT assay. At the same time, glucose uptake and metabolism (ATP and ∆Ψm) in HepG2 cells treated with C. papaya aqueous leaf and root extract were evaluated using a luminometry assay. Additionally, antioxidant properties (SOD2, GPx1, GSH, and Nrf2) were measured using qPCR and Western blot following the detection of MDA, NO, and iNOS, indicators of free radicals. Results: The MTT assay showed that C. papaya extracts did not exhibit toxicity in HepG2 cells and enhanced glucose uptake compared to the hyperglycaemic control (HGC) and metformin. The glucose levels in C. papaya-treated cells increased ATP production (p < 0.05), while the ∆Ψm was significantly increased in HGR1000-treated cells (p < 0.05). Furthermore, C. papaya leaf extract upregulated GPx1 (p < 0.05), GSH, and Nrf2 gene (p < 0.05), while SOD2 and Nrf2 proteins were reduced (p > 0.05), ultimately lowering ROS (p > 0.05). Contrarily, the root extract stimulated SOD2 (p > 0.05), GPx1 (p < 0.05), and GSH levels (p < 0.05), reducing Nrf2 gene and protein expression (p < 0.05) and resulting in high MDA levels (p < 0.05). Additionally, the extracts elevated NO levels and iNOS expression (p < 0.05), suggesting potential RNS activation. Conclusion: Taken together, the leaf extract stimulated glucose metabolism and triggered ROS production, producing a strong antioxidant response that was more effective than the root extract and metformin. However, the root extract, particularly at high concentrations, was less effective at neutralising free radicals as it did not stimulate Nrf2 production, but it did maintain elevated levels of SOD2, GSH, and GPx1 antioxidants.
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Affiliation(s)
- Mthokozisi Bongani Nxumalo
- Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa; (N.N.); (H.M.K.); (R.B.K.)
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Donthula G, Daigavane S. Diabetes Mellitus and Neurovascular Pathology: A Comprehensive Review of Retinal and Brain Lesions. Cureus 2024; 16:e70611. [PMID: 39483560 PMCID: PMC11527494 DOI: 10.7759/cureus.70611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 10/01/2024] [Indexed: 11/03/2024] Open
Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder marked by persistent hyperglycemia, which significantly impacts vascular health. This review comprehensively analyzes the neurovascular complications associated with DM, focusing on retinal and brain lesions. Diabetes is categorized into type 1 DM, type 2 DM, and gestational DM, each presenting unique challenges and risks. The condition accelerates vascular damage through mechanisms such as endothelial dysfunction, inflammation, and oxidative stress, leading to severe microvascular complications. Diabetic retinopathy is a primary concern, with its progression from non-proliferative to proliferative stages potentially resulting in vision loss. Concurrently, diabetes contributes to neurovascular damage in the brain, increasing the risk of cognitive decline and cerebrovascular events. This review examines the pathophysiological mechanisms underlying these complications, evaluates current diagnostic and management strategies, and highlights recent advancements in imaging technologies and therapeutic approaches. Integrating these insights is crucial for improving early detection, treatment, and management of diabetes-related neurovascular issues. Future research should focus on innovative preventive measures and therapeutic interventions to mitigate the long-term impact of diabetes on vascular health. By enhancing our understanding of these complex interactions, this review aims to contribute to better clinical practices and improved patient outcomes in diabetes care.
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Affiliation(s)
- Gayathri Donthula
- Ophthalmology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Sachin Daigavane
- Ophthalmology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
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Rodrigues S, Isabel Patrício A, Cristina C, Fernandes F, Marcelino Santos G, Antunes I, Pintalhão I, Ribeiro M, Lopes R, Moreira S, Oliveira SA, Costa SP, Simões S, Nunes TC, Santiago LM, Rosendo I. Health Literacy and Adherence to Therapy in Type 2 Diabetes: A Cross-Sectional Study in Portugal. Health Lit Res Pract 2024; 8:e194-e203. [PMID: 39378075 DOI: 10.3928/24748307-20240625-01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND Therapy adherence is a key factor in the control of type 2 diabetes mellitus (T2DM). Optimal self-care requires skills in health literacy (HL). OBJECTIVE This study aims to analyze the relationship between HL and adherence to therapy and to understand the possible influence of other sociodemographic and disease variables. METHODS A multicenter, cross-sectional study was conducted in Portuguese in 13 different primary health care units in both rural and urban environments. A sociodemographic questionnaire and two validated instruments, "Medical Term Recognition Test" and "Summary of Diabetes Self-Care Activities," were applied. The last value of hemoglobin A1c (HbA1c) and the number of chronic medications were collected from clinical records. Descriptive statistics and bivariate correlations were performed as well as multivariable linear regression to assess the association between HL and adherence to therapy. KEY RESULTS Participants (n = 354) were on average age 63.67 ± 10.39 years, 57.1% male and 42.9% female, 68.4% with inadequate HL and an average HbA1c of 7 ± 1.18%. Better HL was correlated with higher adherence to the total of self-care activities, nonpharmacological therapy, and foot care. In multivariable linear regression analyses, better HL (β = 0.176, p = .003), less than minimum wage (β = -0.197, p = .001) and insulin therapy (β = 0.272, p = .001) were independently associated with increased adherence to overall self-care activities. CONCLUSION In a representative sample of people with T2DM in Portugal, HL was a key factor for greater adherence to demanding self-care activities. [HLRP: Health Literacy Research and Practice. 2024;8(4):e194-e203.].
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Odimegwu CL, Uwaezuoke SN, Chikani UN, Mbanefo NR, Adiele KD, Nwolisa CE, Eneh CI, Ndiokwelu CO, Okpala SC, Ogbuka FN, Odo KE, Ohuche IO, Obiora-Izuka CE. Targeting the Epigenetic Marks in Type 2 Diabetes Mellitus: Will Epigenetic Therapy Be a Valuable Adjunct to Pharmacotherapy? Diabetes Metab Syndr Obes 2024; 17:3557-3576. [PMID: 39323929 PMCID: PMC11423826 DOI: 10.2147/dmso.s479077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 08/03/2024] [Indexed: 09/27/2024] Open
Abstract
Although genetic, environmental, and lifestyle factors largely contribute to type 2 diabetes mellitus (T2DM) risk, the role of epigenetics in its pathogenesis is now well established. The epigenetic mechanisms in T2DM mainly consist of DNA methylation, histone modifications and regulation by noncoding RNAs (ncRNAs). For instance, DNA methylation at CpG islands in the promoter regions of specific genes encoding insulin signaling and glucose metabolism suppresses these genes. Modulating the enzyme mediators of these epigenetic marks aims to restore standard gene expression patterns and improve glycemic control. In targeting these epigenetic marks, using epigenetic drugs such as DNA methyltransferase (DNAMT), histone deacetylase (HDAC) and histone acetyltransferase (HAT) inhibitors has led to variable success in humans and experimental murine models. Specifically, the United States' Food and Drug Administration (US FDA) has approved DNAMT inhibitors like 5-azacytidine and 5-aza-2'-deoxycytidine for use in diabetic retinopathy: a T2DM microvascular complication. These DNAMT inhibitors block the genes for methylation of mitochondrial superoxide dismutase 2 (SOD2) and matrix metallopeptidase 9 (MMP-9): the epigenetic marks in diabetic retinopathy. Traditional pharmacotherapy with metformin also have epigenetic effects in T2DM and positively alter disease outcomes when combined with epigenetic drugs like DNAMT and HDAC inhibitors, raising the prospect of using epigenetic therapy as a valuable adjunct to pharmacotherapy. However, introducing small interfering RNAs (siRNAs) in cells to silence specific target genes remains in the exploratory phase. Future research should focus on regulating gene expression in T2DM using long noncoding RNA (lncRNA) molecules, another type of ncRNA. This review discusses the epigenetics of T2DM and that of its macro- and microvascular complications, and the potential benefits of combining epigenetic therapy with pharmacotherapy for optimal results.
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Affiliation(s)
- Chioma Laura Odimegwu
- Department of Pediatrics, the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla Enugu, Nigeria
| | - Samuel Nkachukwu Uwaezuoke
- Department of Pediatrics, the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla Enugu, Nigeria
| | - Ugo N Chikani
- Department of Pediatrics, the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla Enugu, Nigeria
| | - Ngozi Rita Mbanefo
- Department of Pediatrics, the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla Enugu, Nigeria
| | - Ken Daberechi Adiele
- Department of Pediatrics, the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla Enugu, Nigeria
| | | | - Chizoma Ihuarula Eneh
- Department of Pediatrics, Enugu State University Teaching Hospital (ESUTH), Enugu, Nigeria
| | - Chibuzo Obiora Ndiokwelu
- Department of Pediatrics, the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla Enugu, Nigeria
| | - Somkenechi C Okpala
- Department of Pediatrics, the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla Enugu, Nigeria
| | - Francis N Ogbuka
- Department of Pediatrics, Enugu State University Teaching Hospital (ESUTH), Enugu, Nigeria
| | - Kenneth E Odo
- Department of Pediatrics, the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla Enugu, Nigeria
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Rugera SP, Tumusiime J, Mudondo H, Naruhura G, Kiconco R, Nkubi Bagenda C. Serum Uric Acid and Microalbuminuria: Predictors of Renal Dysfunction in Type 2 Diabetes Patients in South-Western Uganda. Cureus 2024; 16:e69843. [PMID: 39435249 PMCID: PMC11492550 DOI: 10.7759/cureus.69843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/21/2024] [Indexed: 10/23/2024] Open
Abstract
Background Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by insulin resistance and high blood glucose levels, which has become a global pandemic in recent decades and is associated with several health complications, including renal dysfunction. Serum uric acid levels are associated with kidney damage and have been linked to various health conditions. Urine microalbumin is a sensitive marker of kidney damage and is commonly used to monitor renal dysfunction in diabetes. The study aimed to compare the predictive value of serum uric acid and urine microalbumin in detecting kidney damage among T2D patients. Method This secondary data analysis used a cross-sectional dataset of 140 diabetic patients from Mbarara Regional Referral Hospital (MRRH) in Mbarara, Uganda. The main outcome was renal dysfunction, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m². Key variables included serum uric acid, urinary microalbumin, and various demographic and clinical factors. Data were analyzed using logistic regression and receiver operating characteristic (ROC) curve analysis to evaluate predictive performance. Ethics approval was obtained from the Mbarara University Research Ethics Committee. Results This study involved 140 participants with a median age of 53 years (interquartile range (IQR) 44-60.5), predominantly females (95, 67.9%), primarily educated (76, 54.3%), and mostly married (104, 74.3%). Participants with renal dysfunction were older (median age 61 years, IQR 52-69) compared to those without (median age 49, IQR 40-56), with significant differences in urinary microalbumin and serum uric acid levels (p <0.05). Renal dysfunction prevalence was 33.6% (95% CI: 26.2-41.9), higher in participants with diabetes duration ≥5 years, microalbuminuria, certain marital statuses, and higher diastolic blood pressure. Microalbuminuria (adjusted odds ratio (aOR) 4.71, 95% CI: 1.27-17.50, P = 0.021) and serum uric acid (aOR 1.01, 95% CI: 1.0002-1.0153, P = 0.045) were significantly associated with renal dysfunction. Other associated factors included age, female gender, and diastolic hypertension. Both biomarkers had significant predictive power for renal dysfunction (area under the curve (AUC) 0.62 and 0.65, respectively). Conclusion This study confirms the high prevalence of renal dysfunction among T2D patients, with a finding of 33.6%. The significant association between microalbuminuria and renal dysfunction, as well as the predictive capacity of serum uric acid and urinary microalbumin, highlight the importance of these biomarkers in identifying individuals at risk of kidney complications.
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Affiliation(s)
- Simon Peter Rugera
- Department of Medical Laboratory Science, Mbarara University of Science and Technology, Mbarara, UGA
| | - Jazira Tumusiime
- Department of Medical Laboratory Science, Mbarara University of Science and Technology, Mbarara, UGA
| | - Hope Mudondo
- Department of Medical Laboratory Science, Mbarara University of Science and Technology, Mbarara, UGA
| | - Georgina Naruhura
- Department of Medical Laboratory Science, Mbarara University of Science and Technology, Mbarara, UGA
| | - Ritah Kiconco
- Department of Biochemistry, Soroti University, Soroti, UGA
- Department of Medical Laboratory Science, Mbarara University of Science and Technology, Mbarara, UGA
| | - Charles Nkubi Bagenda
- Department of Medical Laboratory Science, Mbarara University of Science and Technology, Mbarara, UGA
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50
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Su J, Xu J, Hu S, Ye H, Xie L, Ouyang S. Advances in small-molecule insulin secretagogues for diabetes treatment. Biomed Pharmacother 2024; 178:117179. [PMID: 39059347 DOI: 10.1016/j.biopha.2024.117179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/16/2024] [Accepted: 07/22/2024] [Indexed: 07/28/2024] Open
Abstract
Diabetes, a metabolic disease caused by abnormally high levels of blood glucose, has a high prevalence rate worldwide and causes a series of complications, including coronary heart disease, stroke, peripheral vascular disease, end-stage renal disease, and retinopathy. Small-molecule compounds have been developed as drugs for the treatment of diabetes because of their oral advantages. Insulin secretagogues are a class of small-molecule drugs used to treat diabetes, and include sulfonylureas, non-sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and other novel small-molecule insulin secretagogues. However, many small-molecule compounds cause different side effects, posing huge challenges to drug monotherapy and drug selection. Therefore, the use of different small-molecule drugs must be improved. This article reviews the mechanism, advantages, limitations, and potential risks of small-molecule insulin secretagogues to provide future research directions on small-molecule drugs for the treatment of diabetes.
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Affiliation(s)
- Jingqian Su
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China.
| | - Jingran Xu
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China
| | - Shan Hu
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China
| | - Hui Ye
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China
| | - Lian Xie
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China
| | - Songying Ouyang
- Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China.
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