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Ghafourian MS, Tarkiani S, Ghajar M, Chavooshi M, Khormaei H, Ramezani A. Optimizing warfarin dosing in diabetic patients through BERT model and machine learning techniques. Comput Biol Med 2025; 186:109755. [PMID: 39879806 DOI: 10.1016/j.compbiomed.2025.109755] [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: 11/23/2024] [Revised: 01/09/2025] [Accepted: 01/24/2025] [Indexed: 01/31/2025]
Abstract
This study highlights the importance of evaluating warfarin dosing in diabetic patients, who require careful anticoagulation management. With rising rates of diabetes and cardiovascular diseases, understanding the factors influencing warfarin therapy is vital for improving patient outcomes and reducing adverse events. Data was sourced from the IWPC dataset, examining characteristics such as age, gender, diabetes status, indication for warfarin, weight, and height. We utilized the Bidirectional Encoder Representations from Transformers (BERT) model to analyze therapeutic doses, leveraging its ability to understand contextual relationships in the data. A machine learning approach was essential for predicting appropriate warfarin dosages, employing algorithms like Random Forest, KNN, MLP, Linear Regression, and SVM classification. We allocated 20 % of the data for testing and 80 % for training. Results showed that Linear Regression performed less effectively than MLP, KNN, SVM, and Random Forest in both training and testing. Notably, Random Forest's training MAE was significantly lower, while the other models showed similar performance in predicting warfarin dosages. This study emphasizes the importance of personalized anticoagulation management for diabetic patients on warfarin. The application of the BERT model alongside machine learning algorithms, particularly Random Forest, demonstrated effectiveness in predicting appropriate dosages. These findings suggest that integrating these advanced models into clinical practice can enhance decision-making, optimize patient outcomes, and reduce adverse events.
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Affiliation(s)
- Mandana Sadat Ghafourian
- Electrical Engineering Department, Faculty of Engineering, Ferdowsi University of Mashhad, Mashhad, Iran.
| | - Sara Tarkiani
- Department of Cardiology, Zanjan University of Medical Science, Zanjan, Iran.
| | - Mobina Ghajar
- Department of Cardiology, Zanjan University of Medical Science, Zanjan, Iran.
| | - Mohamad Chavooshi
- Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran.
| | - Hossein Khormaei
- Department of Electrical Engineering, National University of Skills (NUS), Tehran, Iran.
| | - Amin Ramezani
- Department of Medicine (HSRD), Baylor College of Medicine, Houston, TX, USA.
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Kindlovits R, Sousa AC, Viana JL, Milheiro J, Oliveira BMPM, Marques F, Santos A, Teixeira VH. Evaluating the Therapeutic Potential of Exercise in Hypoxia and Low-Carbohydrate, High-Fat Diet in Managing Hypertension in Elderly Type 2 Diabetes Patients: A Novel Intervention Approach. Nutrients 2025; 17:522. [PMID: 39940380 PMCID: PMC11819692 DOI: 10.3390/nu17030522] [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: 01/02/2025] [Revised: 01/20/2025] [Accepted: 01/27/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND/OBJECTIVES Type 2 diabetes mellitus (T2DM) is a chronic condition marked by hyperglycemia, which can affect metabolic, vascular, and hematological parameters. A low-carbohydrate, high-fat (LCHF) diet has been shown to improve glycemic control and blood pressure regulation. Exercise in hypoxia (EH) enhances insulin sensitivity, erythropoiesis, and angiogenesis. The combination of LCHF and EH may offer a promising strategy for managing T2DM and hypertension (HTN), although evidence remains limited. This study aimed to assess the effects of an eight-week normobaric EH intervention at 3000 m simulated altitude combined with an LCHF diet on hematological and lipid profiles, inflammation, and blood pressure in older patients with T2DM and HTN. METHODS Forty-two diabetic patients with HTN were randomly assigned to three groups: (1) control group (control diet + exercise in normoxia), (2) EH group (control diet + EH), and (3) intervention group (EH+LCHF) Baseline and eight-week measurements included systolic, diastolic, and mean blood pressure (SBP, DBP, MAP), hematological and lipid profiles, and inflammation biomarkers. RESULTS Blood pressure decreased after the intervention (p < 0.001), with no significant differences between groups (SBP: p = 0.151; DBP: p = 0.124; MAP: p = 0.18). No differences were observed in lipid profile or C-reactive protein levels (p > 0.05). Mean corpuscular hemoglobin (MCH) increased in the EH group (p = 0.027), while it decreased in the EH+LCHF group (p = 0.046). CONCLUSIONS Adding hypoxia or restricting carbohydrates did not provide additional benefits on blood pressure in T2DM patients with HTN. Further elucidation of the mechanisms underlying hematological adaptations is imperative. TRIAL REGISTRATION NUMBER NCT05094505.
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Affiliation(s)
- Raquel Kindlovits
- Faculty of Nutrition and Food Sciences (FCNAUP), University of Porto, 4200-465 Porto, Portugal; (B.M.P.M.O.); (A.S.); (V.H.T.)
| | - Ana Catarina Sousa
- Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD), University of Maia, 4475-690 Maia, Portugal; (A.C.S.); (J.L.V.)
| | - João Luís Viana
- Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD), University of Maia, 4475-690 Maia, Portugal; (A.C.S.); (J.L.V.)
| | - Jaime Milheiro
- Exercise Medical Centre Laboratory (CMEP), 4150-044 Porto, Portugal;
- Centre of Research, Education, Innovation and Intervention in Sport (CIFI2D), Faculty of Sport, University of Porto, 4200-540 Porto, Portugal
| | - Bruno M. P. M. Oliveira
- Faculty of Nutrition and Food Sciences (FCNAUP), University of Porto, 4200-465 Porto, Portugal; (B.M.P.M.O.); (A.S.); (V.H.T.)
- Laboratory of Artificial Intelligence and Decision Support, Institute for Systems and Computer Engineering, Technology and Science (LIAAD, INESC-TEC), 4200-465 Porto, Portugal
| | - Franklim Marques
- Laboratory of Biochemistry, Department of Biological Sciences, UCIBIO, REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal;
| | - Alejandro Santos
- Faculty of Nutrition and Food Sciences (FCNAUP), University of Porto, 4200-465 Porto, Portugal; (B.M.P.M.O.); (A.S.); (V.H.T.)
- Institute for Research and Innovation in Health (i3S), 4200-135 Porto, Portugal
| | - Vitor Hugo Teixeira
- Faculty of Nutrition and Food Sciences (FCNAUP), University of Porto, 4200-465 Porto, Portugal; (B.M.P.M.O.); (A.S.); (V.H.T.)
- Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports (FADEUP), University of Porto, 4200-540 Porto, Portugal
- Laboratory for Integrative and Translational Research in Population Health (ITR), 4050-600 Porto, Portugal
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Zhang H, Chen M, Sun L, Zhu W, Niu T, Fareeduddin Mohammmed Farooqui H, Wang H, Song B, Wang J, Zhang H. The role of activated partial thrombin time in mediating the impact of poorly glycemic control on diabetic peripheral neuropathy in patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne) 2025; 16:1501323. [PMID: 39917541 PMCID: PMC11798803 DOI: 10.3389/fendo.2025.1501323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 01/02/2025] [Indexed: 02/09/2025] Open
Abstract
Aim This study aims to investigate the role of activated partial thrombin time (APTT) as a potential mediator in the relationship between suboptimal glycemic control and diabetic peripheral neuropathy (DPN) in individuals with type 2 diabetes mellitus (T2DM). Methods A total of 183 T2DM patients were enrolled in this study. Comprehensive clinical data, including coagulation parameters and nerve conduction velocity, were collected and compared between patients with and without DPN. Subsequent correlation and regression analyses were conducted to explore the associations among APTT, HbA1c levels, and nerve conduction velocities. Moreover, mediation analyses were performed to evaluate the total, direct, and indirect effects of HbA1c on specific nerve conduction velocities, with APTT serving as a mediator. Results In comparison to 101 patients without DPN, 82 patients with DPN exhibited significantly elevated levels of HbA1c and decreased levels of APTT. Notably, levels of APTT and HbA1c were correlated with conduction velocities of Tibial nerve motor fibers, as well as sensory fibers of the Ulnar nerve, Median nerve, and Sural nerve. Furthermore, both elevated HbA1c and decreased APTT were identified as risk factors for DPN in T2DM individuals. Mediation analysis showed that APTT mediated the indirect effect of HbA1c on the conduction velocities of sensory fibers in both the ulnar nerve and sural nerve (95% CI: -0.3448, -0.0135; -0.3523, -0.0180). APTT mediated the relationship between HbA1c and the conduction velocities of sensory fibers in the ulnar nerve or sural nerve by 34.66% or 22.03%, respectively. Conclusions In patients with T2DM, uncontrolled HbA1c and shorter APTT emerges as risk factors for DPN. Additionally, the effect of increased HbA1c upon DPN, especially for influenced conduction velocities of sensory fibers in both the ulnar nerve and sural nerve may partly medicated by decreased APTT.
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Affiliation(s)
- Hui Zhang
- Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Minghui Chen
- Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Lijie Sun
- Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Wenwen Zhu
- Department of Endocrinology, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, China
- Affiliated Zhongda Hospital of Southeast University, Nanjing, China
| | - Tong Niu
- Affiliated Zhongda Hospital of Southeast University, Nanjing, China
| | | | - Hongxiao Wang
- Department of Endocrinology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Bing Song
- Department of Endocrinology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Jumei Wang
- Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Haoqiang Zhang
- Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
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Datta D, Kundu R, Basu R, Chakrabarti P. Pathophysiological hallmarks in type 2 diabetes heterogeneity (review). Diabetol Int 2024. [DOI: 10.1007/s13340-024-00783-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 10/21/2024] [Indexed: 01/03/2025]
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Orrin M, Barber E, Grainge MJ. Pre-Existing and Gestational Diabetes and Risk of Maternal Venous Thromboembolism: A Systematic Review and Meta-Analysis of Observational Studies. BJOG 2024. [PMID: 39686826 DOI: 10.1111/1471-0528.18043] [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: 08/01/2024] [Revised: 11/28/2024] [Accepted: 12/04/2024] [Indexed: 12/18/2024]
Abstract
BACKGROUND Women who are pregnant are at increased risk of venous thromboembolism (VTE), which persists for up to 3 months following childbirth. Diabetes is known to increase the risk of serious cardiovascular outcomes. OBJECTIVE To comprehensively review literature on the extent to which pre-existing or gestational diabetes influences the risk of VTE in both pregnancy and postpartum. SEARCH STRATEGY We used Medline, Embase and Google Scholar to identify observational studies published up to 2 November 2023. SELECTION CRITERIA Studies which quantified the relationship between diabetes on antepartum and/or postpartum VTE, and which provide separate data for pre-existing and gestational diabetes. DATA COLLECTION AND ANALYSIS Results were pooled, where appropriate, using random-effects meta-analysis. MAIN RESULTS Twenty one studies from Europe, the United States and Asia were included. There was an increased risk of antepartum VTE in women with gestational diabetes (RR = 2.48, 95% CI 1.47 - 4.16, I2= 45%, 4 studies) but not pre-existing diabetes (RR = 1.71, 0.43 - 6.77, I2= 68%, 2 studies). For postpartum VTE, there was no clear association with either pre-existing (RR = 1.28, 0.73 - 2.24, I2= 73%, 6 studies) or gestational (RR = 1.39, 0.77 - 2.51, I2= 70%, 10 studies) diabetes. CONCLUSIONS Our results will provide some reassurance for pregnant women with pre-existing or gestational diabetes, owing to no clear evidence of an increased risk of maternal VTE. While some studies report a raised risk of VTE during antepartum specifically, results must be interpreted in light of high levels of heterogeneity.
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Affiliation(s)
- Molly Orrin
- Academic Unit of Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK
| | - Emilia Barber
- Academic Unit of Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK
| | - Matthew J Grainge
- Academic Unit of Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK
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Tiwari D, Aw TC. Emerging Role of Natriuretic Peptides in Diabetes Care: A Brief Review of Pertinent Recent Literature. Diagnostics (Basel) 2024; 14:2251. [PMID: 39410655 PMCID: PMC11476269 DOI: 10.3390/diagnostics14192251] [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: 09/18/2024] [Revised: 10/07/2024] [Accepted: 10/08/2024] [Indexed: 10/20/2024] Open
Abstract
Diabetes markedly increases susceptibility to adverse cardiovascular events, including heart failure (HF), leading to heightened morbidity and mortality rates. Elevated levels of natriuretic peptides (NPs), notably B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP), correlate with cardiac structural and functional abnormalities, aiding in risk stratification and treatment strategies in individuals with diabetes. This article reviews the intricate relationship between diabetes and HF, emphasizing the role of NPs in risk assessment and guiding therapeutic strategies, particularly in individuals with type 2 diabetes mellitus (T2DM). We also explore the analytical and clinical considerations in the use of natriuretic peptide testing and the challenges and prospects of natriuretic-peptide-guided therapy in managing cardiovascular risk in patients with diabetes. We conclude with some reflections on future prospects for NPs.
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Affiliation(s)
| | - Tar Choon Aw
- Department of Laboratory Medicine, Changi General Hospital, Singapore 529889, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore 119228, Singapore
- Pathology Academic Clinical Program, Duke-NUS Graduate School of Medicine, Singapore 169857, Singapore
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Walczak K, Grzybowska-Adamowicz J, Stawski R, Brzezińska O, Zmysłowska A, Nowak D. Response of Circulating Free Cellular DNA to Repeated Exercise in Men with Type 1 Diabetes Mellitus. J Clin Med 2024; 13:5859. [PMID: 39407919 PMCID: PMC11477321 DOI: 10.3390/jcm13195859] [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: 07/24/2024] [Revised: 09/02/2024] [Accepted: 09/26/2024] [Indexed: 10/20/2024] Open
Abstract
Background: Intense exercise leads to neutrophil extracellular traps (NETs) formation, which triggers cell disintegration. NET, as well as other processes of apoptosis, necrosis, and spontaneous secretion, result in increased levels of cell-free DNA (cf-DNA) in the circulation. An increment of cf-DNA is also observed in autoimmune diseases, such as type 1 diabetes mellitus (T1DM). Repeated exhaustive exercises are an impulse for physiological adaptation; therefore, in this case-control study, we compared the exercise-induced increase in cf-DNA in men with T1DM and healthy controls to determine the development of the tolerance to exercise. Methods: Volunteers performed a treadmill run to exhaustion at a speed matching 70% of their personal VO2 max at three consecutive visits, separated by a 72 h resting period. Blood was collected before and after exercise for the determination of plasma cell-free nuclear and mitochondrial DNA (cf n-DNA, cf mt-DNA) by real-time PCR, blood cell count and metabolic markers. Results: Each bout of exhaustive exercise induced a great elevation of cf n-DNA levels. An increase in cf mt-DNA was observed after each run. However, the significance of the increase was noted only after the second bout in T1DM participants (p < 0.02). Changes in cf-DNA concentration were transient and returned to baseline values during 72 h of resting. The exercise-induced increment in circulating cf n-DNA and cf mt-DNA was not significantly different between the studied groups (p > 0.05). Conclusions: Cf-DNA appears to be a sensitive marker of inflammation, with a lower post-exercise increase in individuals with T1DM than in healthy men.
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Affiliation(s)
- Konrad Walczak
- Department of Internal Medicine and Nephrodiabetology, Medical University of Lodz, 90-549 Lodz, Poland
| | | | - Robert Stawski
- Department of Clinical Physiology, Medical University of Lodz, 92-215 Lodz, Poland
| | - Olga Brzezińska
- Department of Rheumatology, Medical University of Lodz, 90-549 Lodz, Poland
| | - Agnieszka Zmysłowska
- Department of Clinical Genetics, Medical University of Lodz, 92-213 Lodz, Poland
| | - Dariusz Nowak
- Department of Clinical Physiology, Medical University of Lodz, 92-215 Lodz, Poland
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Borbély RZ, Szalai EÁ, Philip BM, Dobszai D, Teutsch B, Zolcsák Á, Veres DS, Erőss B, Gellért B, Hegyi PJ, Hegyi P, Faluhelyi N. The risk of developing splanchnic vein thrombosis in acute pancreatitis increases 3 days after symptom onset: A systematic review and meta-analysis. United European Gastroenterol J 2024; 12:678-690. [PMID: 38400822 PMCID: PMC11250419 DOI: 10.1002/ueg2.12550] [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: 10/16/2023] [Accepted: 01/12/2024] [Indexed: 02/26/2024] Open
Abstract
BACKGROUND Splanchnic vein thrombosis is a complication of acute pancreatitis (AP) and is likely often underdiagnosed. OBJECTIVES We aimed to understand the time course and risk factors of splanchnic vein thrombosis in the early phase of AP. METHODS A systematic search was conducted using the PRISMA guidelines (PROSPERO registration CRD42022367578). Inclusion criteria were appropriate imaging techniques in adult AP patients, studies that reported splanchnic vein thrombosis data from the early phase, and reliable information on the timing of imaging in relation to the onset of pancreatitis symptoms or hospital admission. The proportion of patients with thrombosis with 95% confidence intervals (CI) was calculated using random-effects meta-analyses, and multiple subgroup analyses were performed. RESULTS Data from 1951 patients from 14 studies were analyzed. The proportion of patients with splanchnic vein thrombosis within 12 days after symptom onset was 0.13 (CI 0.07-0.23). The occurrence was lowest at 0.06 (CI 0.03-0.1) between 0 and 3 days after symptom onset, and increased fourfold to 0.23 (CI 0.16-0.31) between 3 and 11 days. On hospital admission, the proportion of patients affected was 0.12 (CI 0.02-0.49); it was 0.17 (CI 0.03-0.58) 1-5 days after admission. The prevalence in mild, moderate, and severe AP was 0.15 (CI 0.05-0.36), 0.26 (CI 0.15-0.43), and 0.27 (CI 0.17-0.4), respectively. Alcoholic etiology (0.31, CI 0.13-0.58) and pancreatic necrosis (0.55, CI 0.29-0.78, necrosis above 30%) correlated with increased SVT prevalence. CONCLUSION The risk of developing splanchnic vein thrombosis is significant in the early stages of AP and may affect up to a quarter of patients. Alcoholic etiology, pancreatic necrosis, and severity may increase the prevalence of splanchnic vein thrombosis.
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Affiliation(s)
- Ruben Zsolt Borbély
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Department of Medical ImagingBajcsy‐Zsilinszky Hospital and ClinicBudapestHungary
| | - Eszter Ágnes Szalai
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Department of Restorative Dentistry and EndodonticsSemmelweis UniversityBudapestHungary
| | | | - Dalma Dobszai
- Institute for Translational MedicineMedical SchoolUniversity of PécsPécsHungary
| | - Brigitta Teutsch
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Institute for Translational MedicineMedical SchoolUniversity of PécsPécsHungary
| | - Ádám Zolcsák
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Department of Biophysics and Radiation BiologySemmelweis UniversityBudapestHungary
| | - Dániel Sándor Veres
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Department of Biophysics and Radiation BiologySemmelweis UniversityBudapestHungary
| | - Bálint Erőss
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Institute for Translational MedicineMedical SchoolUniversity of PécsPécsHungary
- Institute of Pancreatic DiseasesSemmelweis UniversityBudapestHungary
| | - Bálint Gellért
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Department of SurgeryTransplantation and GastroenterologySemmelweis UniversityBudapestHungary
| | - Péter Jenő Hegyi
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Institute of Pancreatic DiseasesSemmelweis UniversityBudapestHungary
| | - Péter Hegyi
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Institute for Translational MedicineMedical SchoolUniversity of PécsPécsHungary
- Institute of Pancreatic DiseasesSemmelweis UniversityBudapestHungary
- Translational Pancreatology Research GroupInterdisciplinary Centre of Excellence for Research Development and InnovationUniversity of SzegedSzegedHungary
| | - Nándor Faluhelyi
- Centre for Translational MedicineSemmelweis UniversityBudapestHungary
- Department of Medical ImagingMedical SchoolUniversity of PécsPécsHungary
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Kaddour N, Benyettou F, Moulai K, Mebarki A, Allal-Taouli K, Ghemrawi R, Whelan J, Merzouk H, Trabolsi A, Mokhtari-Soulimane NA. Effects of subcutaneous vs. oral nanoparticle-mediated insulin delivery on hemostasis disorders in type 1 diabetes: A rat model study. Heliyon 2024; 10:e30450. [PMID: 38711655 PMCID: PMC11070859 DOI: 10.1016/j.heliyon.2024.e30450] [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: 01/18/2024] [Revised: 04/06/2024] [Accepted: 04/26/2024] [Indexed: 05/08/2024] Open
Abstract
Complications associated with Type 1 diabetes (T1D) have complex origins that revolve around chronic hyperglycemia; these complications involve hemostasis disorders, coagulopathies, and vascular damage. Our study aims to develop innovative approaches to minimize these complications and to compare the outcomes of the new approach with those of traditional methods. To achieve our objective, we designed novel nanoparticles comprising covalent organic frameworks (nCOF) loaded with insulin, termed nCOF/Insulin, and compared it to subcutaneous insulin to elucidate the influence of insulin delivery methods on various parameters, including bleeding time, coagulation factors, platelet counts, cortisol plasma levels, lipid profiles, and oxidative stress parameters. Traditional subcutaneous insulin injections exacerbated hemostasis disorder and vascular injuries in streptozotocin (STZ)-induced diabetic rats through increasing plasma triglycerides and lipid peroxidation. Conversely, oral delivery of nCOF/Insulin ameliorated hemostatic disorders and restored the endothelial oxidant/antioxidant balance by reducing lipid peroxidation and enhancing the lipid profile. Our study pioneers the understanding of how STZ-induced diabetes disrupts bleeding time, induces a hypercoagulable state, and causes vascular damage through lipid peroxidation. Additionally, it provides the first evidence for the involvement of subcutaneous insulin treatment in exacerbating vascular and hemostasis disorders in type 1 diabetes (T1D). Introducing an innovative oral insulin delivery via the nCOF approach represents a potential paradigm shift in diabetes management and patient care and promises to improve treatment strategies for type 1 Diabetes.
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Affiliation(s)
- Nawel Kaddour
- Laboratory of Physiology, Physiopathology, and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe (SNVSTU) University of Tlemcen BP 119, Rocade 2 Mansourah, Tlemcen, 13000, Algeria
| | - Farah Benyettou
- New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
| | - Kawtar Moulai
- Laboratory of Physiology, Physiopathology, and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe (SNVSTU) University of Tlemcen BP 119, Rocade 2 Mansourah, Tlemcen, 13000, Algeria
| | - Abdelouahab Mebarki
- Laboratory of Physiology, Physiopathology, and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe (SNVSTU) University of Tlemcen BP 119, Rocade 2 Mansourah, Tlemcen, 13000, Algeria
| | | | - Rose Ghemrawi
- College of Pharmacy, Al Ain University, Abu Dhabi P.O. Box 112612, United Arab Emirates
- AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi P.O. Box 112612, United Arab Emirates
| | - Jamie Whelan
- New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
| | - Hafida Merzouk
- Laboratory of Physiology, Physiopathology, and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe (SNVSTU) University of Tlemcen BP 119, Rocade 2 Mansourah, Tlemcen, 13000, Algeria
| | - Ali Trabolsi
- New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates
| | - Nassima Amel Mokhtari-Soulimane
- Laboratory of Physiology, Physiopathology, and Biochemistry of Nutrition, Department of Biology, Faculty of Natural and Life Sciences, Earth and Universe (SNVSTU) University of Tlemcen BP 119, Rocade 2 Mansourah, Tlemcen, 13000, Algeria
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Yu C, Lin YM, Xian GZ. Hemoglobin loss method calculates blood loss during pancreaticoduodenectomy and predicts bleeding-related risk factors. World J Gastrointest Surg 2024; 16:419-428. [PMID: 38463360 PMCID: PMC10921204 DOI: 10.4240/wjgs.v16.i2.419] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 12/26/2023] [Accepted: 01/19/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND The common clinical method to evaluate blood loss during pancreaticoduodenectomy (PD) is visual inspection, but most scholars believe that this method is extremely subjective and inaccurate. Currently, there is no accurate, objective method to evaluate the amount of blood loss in PD patients. AIM The hemoglobin (Hb) loss method was used to analyze the amount of blood loss during PD, which was compared with the blood loss estimated by traditional visual methods. The risk factors for bleeding were also predicted at the same time. METHODS We retrospectively analyzed the clinical data of 341 patients who underwent PD in Shandong Provincial Hospital from March 2017 to February 2019. According to different surgical methods, they were divided into an open PD (OPD) group and a laparoscopic PD (LPD) group. The differences and correlations between the intraoperative estimation of blood loss (IEBL) obtained by visual inspection and the intraoperative calculation of blood loss (ICBL) obtained using the Hb loss method were analyzed. ICBL, IEBL and perioperative calculation of blood loss (PCBL) were compared between the two groups, and single-factor regression analysis was performed. RESULTS There was no statistically significant difference in the preoperative general patient information between the two groups (P > 0.05). PD had an ICBL of 743.2 (393.0, 1173.1) mL and an IEBL of 100.0 (50.0, 300.0) mL (P < 0.001). There was also a certain correlation between the two (r = 0.312, P < 0.001). Single-factor analysis of ICBL showed that a history of diabetes [95% confidence interval (CI): 53.82-549.62; P = 0.017] was an independent risk factor for ICBL. In addition, the single-factor analysis of PCBL showed that body mass index (BMI) (95%CI: 0.62-76.75; P = 0.046) and preoperative total bilirubin > 200 μmol/L (95%CI: 7.09-644.26; P = 0.045) were independent risk factors for PCBL. The ICBLs of the LPD group and OPD group were 767.7 (435.4, 1249.0) mL and 663.8 (347.7, 1138.2) mL, respectively (P > 0.05). The IEBL of the LPD group 200.0 (50.0, 200.0) mL was slightly greater than that of the OPD group 100.0 (50.0, 300.0) mL (P > 0.05). PCBL was greater in the LPD group than the OPD group [1061.6 (612.3, 1632.3) mL vs 806.1 (375.9, 1347.6) mL] (P < 0.05). CONCLUSION The ICBL in patients who underwent PD was greater than the IEBL, but there is a certain correlation between the two. The Hb loss method can be used to evaluate intraoperative blood loss. A history of diabetes, preoperative bilirubin > 200 μmol/L and high BMI increase the patient's risk of bleeding.
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Affiliation(s)
- Chao Yu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Yi-Min Lin
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
| | - Guo-Zhe Xian
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China
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11
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Bambo GM, Asmelash D, Alemayehu E, Gedefie A, Duguma T, Kebede SS. Changes in selected hematological parameters in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis. Front Med (Lausanne) 2024; 11:1294290. [PMID: 38444411 PMCID: PMC10912516 DOI: 10.3389/fmed.2024.1294290] [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: 09/14/2023] [Accepted: 01/29/2024] [Indexed: 03/07/2024] Open
Abstract
Background Diabetes mellitus is a chronic metabolic disorder that causes hyperglycemia and various life-threatening health problems. Although hematological parameters play a significant role in the progression and pathogenesis of diabetes, many studies have explored contradictory findings. Therefore, this evidence-based study aimed to determine the pooled mean difference of white blood cell and red blood cell parameters in diabetic patients in order to investigate hematological dysfunctions in type 1 and type 2 diabetes mellitus. Methods Articles were extensively searched in bibliographic databases (PubMed, Cochrane library, Scopus, Web of Science, PsycINFO, Embase, online archives and university repositories) using appropriate entry terms. For studies meeting the eligibility criteria, the first author's name, year of publication, study design and area, type of diabetes mellitus, sample size, and mean and standard deviation of hematological parameters were extracted using Microsoft Excel and exported to Stata 11 for meta-analysis. The pooled standardized mean difference (SMD) was determined using the random effects model, and heterogeneity was quantified using Higgins' I2 statistics. Egger's test and funnel plot were performed to measure bias. Furthermore, a sensitivity analysis was performed to determine the small study effect. Results Initially 39, 222 articles were identified. After screening of the entire methodology, 22 articles with 14,041 study participants (6,146 T2DM, 416 T1DM patients and 7,479 healthy controls) were included in this study. The pooled SMD in TLC (109/L) was 0.66 and -0.21, in T2DM and T1DM, respectively. Differences in absolute differential WBC counts for neutrophils, eosinophils, basophils, lymphocytes and monocytes in T2DM were 0.84, -1.59, 3.20, 0.36 and 0.26, respectively. The differences in relative differential counts (%) in T2DM were as follows: neutrophils: 1.31, eosinophils: -0.99, basophils: 0.34, lymphocytes: -0.19 and monocyte: -0.64. The SMD of differential counts of WBC (109/L) parameters; neutrophils, lymphocytes, monocytes and basophils in T1DM were -0.10, -0.69, 0.19, and -0.32, respectively. The pooled SMD in RBC parameters in T2DM were as follows: RBC: -0.57 (106/μL), Hb: -0.73 g/dL and HCT: -1.22%, Where as in T1DM RBC, Hb and HCT were -1.23 (106/μL), -0.80 g/dL and -0.29%, respectively. Conclusion Patients with T2DM had significantly increased TLC counts, absolute neutrophil, basophil, lymphocyte, monocyte counts and relative counts of neutrophils and basophils in comparison to controls. On the contrary, the absolute eosinophil count and relative lymphocyte, eosinophil and monocyte counts were decreased. In T1DM, WBC parameters were significantly decreased except monocytes. RBC parameters were found to be significantly decreased in T2DM patients. In T1DM, Hb and HCT were significantly decreased. However, there is no significant difference in RBC as compared with non-diabetic controls. The findings indicated a significant alteration of WBC and RBC parameters in both diabetic patients suggesting the considerable metabolic effect of diabetes on hematologic parameters. Systematic review registration https://www.crd.york.ac.uk/prospero/export_details_pdf.php, identifier [CRD42023413486].
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Affiliation(s)
- Getachew Mesfin Bambo
- Department of Medical Laboratory Sciences, College of Health Sciences, Mizan-Tepi University, Mīzan, Ethiopia
| | - Daniel Asmelash
- Department of Medical Laboratory Sciences, College of Health Sciences, Mizan-Tepi University, Mīzan, Ethiopia
| | - Ermiyas Alemayehu
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Alemu Gedefie
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Tadesse Duguma
- Department of Medical Laboratory Sciences, College of Health Sciences, Mizan-Tepi University, Mīzan, Ethiopia
| | - Samuel Sahile Kebede
- Department of Medical Laboratory Sciences, College of Health Sciences, Mizan-Tepi University, Mīzan, Ethiopia
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12
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Duman BÖ, Yazir Y, Halbutoğullari ZS, Mert S, Öztürk A, Gacar G, Duruksu G. Production of alginate macrocapsule device for long-term normoglycaemia in the treatment of type 1 diabetes mellitus with pancreatic cell sheet engineering. Biomed Mater 2024; 19:025008. [PMID: 38194706 DOI: 10.1088/1748-605x/ad1c9b] [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: 08/15/2023] [Accepted: 01/09/2024] [Indexed: 01/11/2024]
Abstract
Type 1 diabetes-mellitus (T1DM) is characterized by damage of beta cells in pancreatic islets. Cell-sheet engineering, one of the newest therapeutic approaches, has also been used to create functional islet systems by creating islet/beta cell-sheets and transferring these systems to areas that require minimally invasive intervention, such as extrahepatic areas. Since islets, beta cells, and pancreas transplants are allogeneic, immune problems such as tissue rejection occur after treatment, and patients become insulin dependent again. In this study, we aimed to design the most suitable cell-sheet treatment method and macrocapsule-device that could provide long-term normoglycemia in rats. Firstly, mesenchymal stem cells (MSCs) and beta cells were co-cultured in a temperature-responsive culture dish to obtain a cell-sheet and then the cell-sheets macroencapsulated using different concentrations of alginate. The mechanical properties and pore sizes of the macrocapsule-device were characterized. The viability and activity of cell-sheets in the macrocapsule were evaluatedin vitroandin vivo. Fasting blood glucose levels, body weight, and serum insulin & C-peptide levels were evaluated after transplantation in diabetic-rats. After the transplantation, the blood glucose level at 225 mg dl-1on the 10th day dropped to 168 mg dl-1on the 15th day, and remained at the normoglycemic level for 210 days. In this study, an alginate macrocapsule-device was successfully developed to protect cell-sheets from immune attacks after transplantation. The results of our study provide the basis for future animal and human studies in which this method can be used to provide long-term cellular therapy in T1DM patients.
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Affiliation(s)
- Büşra Öncel Duman
- European Vocational School, Medical Laboratory Techniques Program, Kocaeli Health and Technology University, 41030 Kocaeli, Turkey
| | - Yusufhan Yazir
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
- Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
| | - Zehra Seda Halbutoğullari
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
- Department of Medical Biology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
| | - Serap Mert
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
- Department of Chemistry and Chemical Processing Technology, Kocaeli University, Kocaeli, Turkey
- Department of Polymer Science and Technology, Kocaeli University, Kocaeli, Turkey
| | - Ahmet Öztürk
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
- Department of Histology and Embryology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey
| | - Gülçin Gacar
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
| | - Gökhan Duruksu
- Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University (KOGEM), TR41001 Izmit, Kocaeli, Turkey
- Department of Stem Cell, Institute of Health Sciences, Kocaeli University, Kocaeli, Turkey
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13
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Xiao M, Tang D, Luan S, Hu B, Gong W, Pommer W, Dai Y, Yin L. Dysregulated coagulation system links to inflammation in diabetic kidney disease. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2023; 4:1270028. [PMID: 38143793 PMCID: PMC10748384 DOI: 10.3389/fcdhc.2023.1270028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 11/24/2023] [Indexed: 12/26/2023]
Abstract
Diabetic kidney disease (DKD) is a significant contributor to end-stage renal disease worldwide. Despite extensive research, the exact mechanisms responsible for its development remain incompletely understood. Notably, patients with diabetes and impaired kidney function exhibit a hypercoagulable state characterized by elevated levels of coagulation molecules in their plasma. Recent studies propose that coagulation molecules such as thrombin, fibrinogen, and platelets are interconnected with the complement system, giving rise to an inflammatory response that potentially accelerates the progression of DKD. Remarkably, investigations have shown that inhibiting the coagulation system may protect the kidneys in various animal models and clinical trials, suggesting that these systems could serve as promising therapeutic targets for DKD. This review aims to shed light on the underlying connections between coagulation and complement systems and their involvement in the advancement of DKD.
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Affiliation(s)
- Mengyun Xiao
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Donge Tang
- Shenzhen People’s Hospital/The Second Clinical School of Jinan University, Shenzhen, Guangdong, China
| | - Shaodong Luan
- Department of Nephrology, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong, China
| | - Bo Hu
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Wenyu Gong
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Wolfgang Pommer
- KfH Kuratoriumfuer Dialyse und Nierentransplantatione.V., Bildungszentrum, Neu-Isenburg, Germany
| | - Yong Dai
- The First Affiliated Hospital, School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China
| | - Lianghong Yin
- Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
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14
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Ferdous J, Rahman ME, Sraboni FS, Dutta AK, Rahman MS, Ali MR, Sikdar B, Khan A, Hasan MF. Assessment of the hypoglycemic and anti-hemostasis effects of Paederia foetida (L.) in controlling diabetes and thrombophilia combining in vivo and computational analysis. Comput Biol Chem 2023; 107:107954. [PMID: 37738820 DOI: 10.1016/j.compbiolchem.2023.107954] [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: 07/31/2023] [Revised: 09/03/2023] [Accepted: 09/05/2023] [Indexed: 09/24/2023]
Abstract
Paederia foetida is valued for its folk medicinal properties. This research aimed to assess the acute toxicity, hypoglycemic and anti-hemostasis properties of the methanolic extract of P. foetida leaves (PFLE). Acute toxicity of PFLE was performed on a mice model. Hypoglycemic and anti-hemostasis properties of PFLE were investigated on normal and streptozotocin-induced mice models. Deep learning, molecular docking, density functional theory, and molecular simulation techniques were employed to understand the underlying mechanisms through in silico study. Oral administration of PFLE at a dosage of 300 µg/kg body weight (BW) showed no signs of toxicity. Treatment with PFLE (300 µg/kg/BW) for 14 days resulted in a hypoglycemic condition and a 30.47% increase in body weight. Additionally, PFLE mixed with blood exhibited a 44.6% anti-hemostasis effect. Deep learning predicted the inhibitory concentration (pIC50, nM) of Cleomiscosins against SGLT2 and FXa to be 7.478 and 6.017, respectively. Molecular docking analysis revealed strong binding interactions of Cleomiscosins with crucial residues of the target proteins, exhibiting binding energies of -8.2 kcal/mol and -7.1 kcal/mol, respectively. ADME/Tox predictions indicated favorable pharmacokinetic properties of Cleomiscosins, and DFT calculations of frontier molecular orbitals analyzed the stability and reactivity of these compounds. Molecular simulation dynamics, principal component analysis and MM-PBSA calculation demonstrated the stable, compact, and rigid nature of the protein-ligand complexes. The methanolic PFLE exhibited significant hypoglycemic and anti-hemostasis properties. Cleomiscosin may have inhibitory properties for the development of novel drugs to manage diabetes and thrombophilia in the near future.
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Affiliation(s)
- Jannatul Ferdous
- Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh.
| | - Md Ekhtiar Rahman
- Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh.
| | - Farzana Sayed Sraboni
- Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh.
| | - Amit Kumar Dutta
- Department of Microbiology, University of Rajshahi, Rajshahi 6205, Bangladesh.
| | - Md Siddikur Rahman
- Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh.
| | - Md Roushan Ali
- Department of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi 6205, Bangladesh.
| | - Biswanath Sikdar
- Department of Microbiology, University of Rajshahi, Rajshahi 6205, Bangladesh.
| | - Alam Khan
- Department of Pharmacy, University of Rajshahi, Rajshahi 6205, Bangladesh
| | - Md Faruk Hasan
- Department of Microbiology, University of Rajshahi, Rajshahi 6205, Bangladesh.
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15
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Ohkura N, Morimoto-Kamata R, Kamikubo Y, Takahashi Y, Oishi K. Hypofibrinolytic phenotype in Tsumura Suzuki Obese Diabetes (TSOD) mice unrelated to hyperglycemia. Drug Discov Ther 2023; 17:346-350. [PMID: 37839864 DOI: 10.5582/ddt.2023.01064] [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] [Indexed: 10/17/2023]
Abstract
Obesity and diabetes mellitus are associated with increased risk of arterial thrombosis and venous thromboembolism. Tsumura Suzuki Obese Diabetes (TSOD) mice are useful models for elucidating the molecular mechanisms of these diseases. We investigated normoglycemic [Ng]-TSOD mice with a metabolic abnormality that was accompanied by a coagulative and fibrinolytic state with a phenotype that distinctly differed from that of standard TSOD mice. As in TSOD mice, plasminogen activation inhibitor-1 (PAI-1) that inhibits fibrinolysis was substantially augmented in Ng-TSOD mice, suggesting that they are hypofibrinolytic. However, blood clotting parameters were within the normal range in Ng-TSOD mice. These findings indicated that Ng-TSOD mice are novel models with a hypofibrinolytic phenotype that is not associated with hyperglycemia.
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Affiliation(s)
- Naoki Ohkura
- Laboratory of Host Defence, School of Pharma-Sciences, Teikyo University, Tokyo, Japan
| | - Riyo Morimoto-Kamata
- Laboratory of Host Defence, School of Pharma-Sciences, Teikyo University, Tokyo, Japan
| | - Yuichi Kamikubo
- Thrombo Translational Research Lab Inc., Kumamoto University Cooperation Incubator, Minami-Kumamoto, Kumamoto, Japan
| | - Yoshihisa Takahashi
- Department of Pathology, School of Medicine, International University of Health and Welfare, Narita, Japan
| | - Katsutaka Oishi
- Healthy Food Science Research Group, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki, Japan
- Department of Applied Biological Science, Graduate School of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan
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16
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Huang Q, Feng D, Pan L, Wang H, Wu Y, Zhong B, Gong J, Lin H, Fei X. Plasma thrombin-activatable fibrinolysis inhibitor and the 1040C/T polymorphism are risk factors for diabetic kidney disease in Chinese patients with type 2 diabetes. PeerJ 2023; 11:e16352. [PMID: 38025709 PMCID: PMC10655703 DOI: 10.7717/peerj.16352] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 10/04/2023] [Indexed: 12/01/2023] Open
Abstract
Background Inflammatory and hemostatic disorders in diabetic microangiopathy (DMA) can be linked to thrombin-activatable fibrinolysis inhibitor (TAFI) and its own gene polymorphisms. Thus, the study aimed to investigate the associations of plasma TAFI and gene polymorphisms with DMA in Chinese patients with type 2 diabetes (T2D). Methods Plasma TAFI of 223 patients with T2D was measured, and the genotypes and alleles of the 1040C/T, 438G/A, and 505G/A polymorphisms of the TAFI gene were analyzed. A ROC curve was constructed to evaluate the identifying power of TAFI between patients with T2D and DMA, and logistic regression analysis was used to observe the correlation of plasma TAFI and gene polymorphisms with the risk for DMA. Results Plasma TAFI was higher in patients with DMA than in patients with only T2D (p < 0.05). TAFI exhibited the largest area under ROC in identifying diabetic kidney disease (DKD) from only T2D (0.763, 95% CI [0.674-0.853], p < 0.01), and adjusted multivariate analysis showed a high odds ratio (OR: 15.72, 95% CI [4.573-53.987], p < 0.001) for DKD. Higher frequencies of the CT genotype and T allele of the 1040C/T polymorphism were found in DKD compared with only T2D (respectively p < 0.05), and the CT genotype exhibited a high OR (1.623, 95% CI [1.173-2.710], p < 0.05) for DKD. DKD patients with the CT genotype had higher plasma TAFI levels, while T2D and DKD patients with CC/TT genotypes had lower plasma TAFI levels. Conclusion Plasma TAFI and the CT genotype and T allele of the 1040C/T polymorphism are independent risk factors for DKD in Chinese T2D patients.
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Affiliation(s)
- Qinghua Huang
- Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Hangzhou, Zhejiang, China
- Geriatric Medicine Center, Department of Endocrinology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Dujin Feng
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Lianlian Pan
- Department of Laboratory Medicine, Sanmen People’s Hospital, Sanmen, Zhejiang, China
| | - Huan Wang
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yan Wu
- Department of Laboratory Medicine, Lin’an First People’s Hospital, Hangzhou, Zhejiang, China
| | - Bin Zhong
- Department of Laboratory Medicine, The Seventh Cixi Hospital of Ningbo, Cixi, Zhejiang, China
| | - Jianguang Gong
- Laboratory of Kidney Disease, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Huijun Lin
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Xianming Fei
- Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
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17
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Ding C, Guo C, Du D, Gong X, Yuan Y. Association between diabetes and venous thromboembolism: A systematic review and meta-analysis. Medicine (Baltimore) 2023; 102:e35329. [PMID: 37861548 PMCID: PMC10589568 DOI: 10.1097/md.0000000000035329] [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: 03/15/2023] [Accepted: 08/31/2023] [Indexed: 10/21/2023] Open
Abstract
BACKGROUND Diabetes mellitus (DM) plays a vital role in the development of cardiovascular disease. However, its association with venous thromboembolism (VTE) remains unclear, for the published study results are conflicting. We performed a meta-analysis of published cohort studies and case-control studies to assess the role of DM in the formation and prognosis of VTE. METHODS PubMed and EMBASE databases were searched for articles from the database's establishment until September 15, 2022. Of the 15,754 publications retrieved, 50 studies were identified that met the selection criteria. The New castle-Ottawa Scale was used to evaluate the quality of the literature. Pooled odds ratios (ORs) and 95% confidence intervals were calculated using fixed- or random-effect models. RESULTS We combined OR using a random-effects or fixed-effects model: patients with DM had an increased risk of VTE (OR 1.27, 95% confidence interval [CI]: 1.15-1.41), which still showed a partial association in studies adjusted by confounding factors (OR 1.20, 95% CI: 1.07-1.35). DM was not significantly associated with VTE when analyzed in studies adjusted by body mass index (OR 1.04, 95% CI: 0.94-1.15). VTE patients with DM had a higher risk of short-term and long-term mortality than those without DM (OR 1.58 [95% CI: 1.26-1.99] for long-term mortality and OR 1.20 [95% CI: 1.19-1.21] for short-term mortality). CONCLUSION There was no significant association between DM and VTE risk, and body mass index may be a significant confounding factor between DM and VTE risk. However, DM can still lead to an increased risk of long-term and short-term mortality in patients with VTE.
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Affiliation(s)
- Chaowei Ding
- Department of Respiratory and Critical Care Medicine, Xiamen Humanity Hospital Fujian Medical University, Xiamen, Fujian, China
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Chang Guo
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Dan Du
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Xiaowei Gong
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Yadong Yuan
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
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Safdar NZ, Kietsiriroje N, Ajjan RA. The Cellular and Protein Arms of Coagulation in Diabetes: Established and Potential Targets for the Reduction of Thrombotic Risk. Int J Mol Sci 2023; 24:15328. [PMID: 37895008 PMCID: PMC10607436 DOI: 10.3390/ijms242015328] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 10/16/2023] [Accepted: 10/17/2023] [Indexed: 10/29/2023] Open
Abstract
Diabetes is a metabolic condition with a rising global prevalence and is characterised by abnormally high blood glucose levels. Cardiovascular disease (CVD) accounts for the majority of deaths in diabetes and, despite improvements in therapy, mortality and hospitalisations in this cohort remain disproportionally higher compared to individuals with normal glucose metabolism. One mechanism for increased CVD risk is enhanced thrombosis potential, due to altered function of the cellular and acellular arms of coagulation. Different mechanisms have been identified that mediate disordered blood clot formation and breakdown in diabetes, including dysglycaemia, insulin resistance, and metabolic co-morbidities. Collectively, these induce platelet/endothelial dysfunction and impair the fibrinolytic process, thus creating a prothrombotic milieu. Despite these abnormalities, current antithrombotic therapies are largely similar in diabetes compared to those without this condition, which explains the high proportion of patients experiencing treatment failure while also displaying an increased risk of bleeding events. In this narrative review, we aimed to summarise the physiological functioning of haemostasis followed by the pathological effects of diabetes mellitus on platelets and the fibrin network. Moreover, we carefully reviewed the literature to describe the current and future therapeutic targets to lower the thrombosis risk and improve vascular outcomes in diabetes.
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Affiliation(s)
- Nawaz Z. Safdar
- Department of Internal Medicine, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF, UK;
- Light Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 3AA, UK
| | - Noppadol Kietsiriroje
- Endocrinology and Metabolism Unit, Faculty of Medicine, Prince of Songkla University, Songkla 90110, Thailand;
| | - Ramzi A. Ajjan
- Light Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 3AA, UK
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19
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Krause M, De Vito G. Type 1 and Type 2 Diabetes Mellitus: Commonalities, Differences and the Importance of Exercise and Nutrition. Nutrients 2023; 15:4279. [PMID: 37836562 PMCID: PMC10574155 DOI: 10.3390/nu15194279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 09/16/2023] [Indexed: 10/15/2023] Open
Abstract
Diabetes mellitus represents a group of physiological dysfunctions characterized by hyperglycaemia resulting directly from insulin resistance (in the case of type 2 diabetes mellitus-T2DM), inadequate insulin secretion/production, or excessive glucagon secretion (in type 1 diabetes mellitus-T1DM) [...].
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Affiliation(s)
- Maurício Krause
- Laboratório de Inflamação, Metabolismo e Exercício (LAPIMEX) e Laboratório de Fisiologia Celular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, RS, Brazil
| | - Giuseppe De Vito
- Neuromuscular Physiology Laboratory, Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy;
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20
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Essawi K, Dobie G, Shaabi MF, Hakami W, Saboor M, Madkhali AM, Hamami AAH, Allallah WH, Akhter MS, Mobarki AA, Hamali HA. Comparative Analysis of Red Blood Cells, White Blood Cells, Platelet Count, and Indices in Type 2 Diabetes Mellitus Patients and Normal Controls: Association and Clinical Implications. Diabetes Metab Syndr Obes 2023; 16:3123-3132. [PMID: 37822802 PMCID: PMC10563775 DOI: 10.2147/dmso.s422373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 09/04/2023] [Indexed: 10/13/2023] Open
Abstract
Background Diabetes mellitus (DM) is a major health burden affecting 537 million adults worldwide, characterized by chronic metabolic disorder and various complications. This case control study aimed to assess the impact of type 2 diabetes mellitus (T2DM), including hyperglycemia levels, on hematological parameters and complete blood count (CBC) derived parameters. Methods A total of 250 known diabetic patients from the Jazan Diabetic Center, Saudi Arabia, between January 2021 and December 2022, along with 175 healthy adult controls were recruited from Jazan Hospital's blood donation center. Demographic characteristics, medical histories, and relevant factors such as gender, age, BMI, treatment, disease duration, and comorbidities were collected with informed consent. Results The results of the red blood cell (RBC) count, RBC indices, and mean platelet volume showed significant differences between patients and controls, while the white cell (WBC) and platelet count were comparable between the two groups. CBC-derived parameters, especially neutrophil/lymphocyte ratio (NLR), and platelet/neutrophil ratio (PNR) exhibited significant differences. Conclusion CBC and derived parameters serve as inexpensive tools for T2DM patients monitoring, indicating early blood cell alterations and potential development of anemia. Further studies are needed to explore their role in predicting T2DM pathogenesis and progression, aiming to reduce severe complications, mortality and morbidity.
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Affiliation(s)
- Khaled Essawi
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Gasim Dobie
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Misk F Shaabi
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Waleed Hakami
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Muhammad Saboor
- Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Aymen M Madkhali
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Abdullah A H Hamami
- Department of Laboratory & Blood Bank, Prince Mohammed bin Nasser Hospital, Ministry of Health, Jazan, Saudi Arabia
| | - Wael H Allallah
- Department of Laboratory & Blood Bank, Prince Mohammed bin Nasser Hospital, Ministry of Health, Jazan, Saudi Arabia
| | - Mohammad S Akhter
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Abdullah A Mobarki
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
| | - Hassan A Hamali
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
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21
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Abbas AB, Hazeb A, Al-Badani R, Al-Thmary B, Mokaram R, Al-Najjar S, Mothna S, Kssiam A, Esmail A, Al-Rashidi A. A case-control study to evaluate hematological indices in blood of diabetic and non-diabetic individuals in Ibb City, Yemen. Sci Rep 2023; 13:16730. [PMID: 37794107 PMCID: PMC10550932 DOI: 10.1038/s41598-023-43973-3] [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: 07/08/2023] [Accepted: 09/30/2023] [Indexed: 10/06/2023] Open
Abstract
Diabetes mellitus (DM) is a chronic, metabolic illness characterized by an elevation of blood sugar levels. Patients with diabetes show changes in hematological indices. The study aimed to determine hematological indices, ESR, CRP, blood pressure (BP), and weight and their relationship with a fasting blood sugar (FBS) level and different variables in diabetic mellitus patients (DM) compared with healthy control (HC). A total of 202 participants (102 DM group and 100 HC group) were selected randomly. Data were collected using a questionnaire. Blood samples were collected from different places and investigated in Zain Medical Laboratories in Ibb City, Yemen (September 2022 to May 2023). GraphPad Prim was used to analyze the results. P-value ≤ 0.05 was considered statistically significant. The mean and standard deviation of age, weight, gender, residence, marital status, education levels, economic status, regular exercise, following a strict diet, and family history of diabetes revealed significant differences between DM and HC groups (P < 0.0001, P = 0001, P = 0.0027, P = 0.0002, P < 0.0001, P < 0.0001, P = 0.0002, P = 0.0011, P < 0.0001 and P = 0.0001, respectively). FBS results, systolic and diastolic BP, MCV, WBCs, monocytes, eosinophils, and platelets displayed significant differences between both groups (P < 0.0001, P < 0.0001 and P = 0.0404, P = 0.0191, P < 0.0001, P = 0.0253, P < 0.0001, and P = 0.0229, respectively). ESR exhibited statistical significance (P < 0.0001), while CRP displayed no significance. A Pearson's correlation showed that weight, Hb, RBCs, PCV, and WBCs were statistically negatively correlated with FBS whereas other hematological indices showed no correlation with FBS. In conclusion, DM patients had relatively higher levels of MCV, WBCs, eosinophils, platelets and ESR than the control group.
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Affiliation(s)
- Abdul Baset Abbas
- Medical Laboratories Department, Faculty of Medicine and Health Sciences, Ibb University, Ibb City, Yemen.
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen.
| | - Alia Hazeb
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Rawan Al-Badani
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Boshra Al-Thmary
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Rasha Mokaram
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Somayah Al-Najjar
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Shifa Mothna
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Aziza Kssiam
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
| | - Abeer Esmail
- Department of Medical Laboratories, Faculty of Medical Sciences, Aljazeera University, Ibb City, Yemen
- Department of Medical Microbiology, Faculty of Sciences, Ibb University, Ibb City, Yemen
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22
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Gazal G, Elmalky W, Zafar MS. Conduct dental care for uncontrolled diabetic patients during COVID-19 pandemic. J Taibah Univ Med Sci 2023; 18:997-998. [PMID: 36811086 PMCID: PMC9934004 DOI: 10.1016/j.jtumed.2023.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 02/08/2023] [Indexed: 02/18/2023] Open
Affiliation(s)
- Giath Gazal
- Department of Oral and Maxillofacial Surgery, Taibah University, Almadinah Almunawwarah, KSA
| | - Wael Elmalky
- Department of Restorative, Dentistry, Taibah University, Almadinah Almunawwarah, KSA
| | - Muhammad S. Zafar
- Department of Restorative, Dentistry, Taibah University, Almadinah Almunawwarah, KSA,Department of Dental Materials, Islamic International Dental College, Riphah International University, Islamabad, Pakistan,Corresponding address: Department of Restorative, Dentistry, Taibah University, Almadinah Almunawwarah, KSA
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23
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Gangwani MK, Aziz M, Chacko P, Mahmood A, Ali M, Priyanka F, Munir S, Aziz A, Sagheer S, Lee-Smith W, Parkash O, Rai D, Baibhav B, Aronow WS. Short Versus Long Duration of Dual Antiplatelet Therapy After Second-Generation Drug-Eluting Stents Implantation in Patients with Diabetes. Am J Ther 2023; 30:e416-e425. [PMID: 37713685 DOI: 10.1097/mjt.0000000000001519] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Duration of dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) remains uncertain, with increasing data suggestive of acceptable short-term duration. Metabolically accelerated atherosclerosis associated with diabetes makes it essential to study short-term DAPT in this subgroup. With limited studies determining optimal DAPT strategies after second-generation stents in this subset, we aimed to establish the optimal duration of DAPT in the diabetic population using second-generation stents. QUESTION To determine optimal DAPT duration in diabetic population undergoing PCI in 2nd generation stents. DATA SOURCES We conducted an electronic database search of randomized controlled trials from PubMed/Medline, Embase, Cochrane, and Web of Science databases. STUDY DESIGN A meta-analysis was conducted comparing outcomes of short-term (3-6 months) DAPT therapy versus long-term (12 months) DAPT therapy in the diabetic population undergoing PCI with second-generation stents. RESULTS A total of 5 randomized controlled trials were included with a total of 3117 diabetic patients. Short-term DAPT did not show any statistical difference from long-term DAPT in achieving primary outcomes (relative ratio: 0.96, 95% confidence interval (CI) 0.68-1.35, P = 0.84). Overall mortality (OR 0.92; 95% CI, 0.52-1.63, P = 0.98), myocardial infarction [odds ratio (OR)OR 1.02; 95% CI, 0.53-1.94, P = 0.85], stent thrombosis (OR 1.20; 95% CI, 0.55-2.60, P = 0.55), target vessel revascularization (OR 1.10; 95% CI, 0.45-2.73, P = 0.74), and stroke (OR 0.50; 95% CI, 0.082-2.43, P = 0.81) did not show any statistical difference between the 2 groups. Similarly, a subgroup analysis of study population comparing 6 versus 12 months of DAPT in diabetic population did not show any difference in net primary outcomes (relative ratio: 0.86, 95% CI 0.45-1.45, P = 0.60). There was no significant heterogeneity noted between the 2 groups. CONCLUSION This meta-analysis showed no statistically significant benefit of longer DAPT over shorter DAPT therapy in patients undergoing PCI with drug-eluting stent in patients with diabetes.
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Affiliation(s)
| | | | - Paul Chacko
- Cardiology, University of Toledo Medical Center, Toledo, OH
| | | | | | - Fnu Priyanka
- Division of Medicine, Chandka Medical College, Larkana, Pakistan
| | - Siraj Munir
- Department of Medicine, Queen's Hospital, Romford, United Kingdom
| | - Abeer Aziz
- Division of Medicine, Aga Khan University, Karachi, Pakistan
| | - Shazib Sagheer
- Department of Cardiovascular Medicine, University of New Mexico, Albuquerque, NM
| | - Wade Lee-Smith
- Department of Toledo Libraries, University of Toledo, Toledo, OH
| | - Om Parkash
- Icahn School of Medicine, Mount Sinai Hospital, New York, NY
| | - Devesh Rai
- Department of Cardiology, Rochester General Hospital, Rochester, NY; and
| | - Bipul Baibhav
- Department of Cardiology, Rochester General Hospital, Rochester, NY; and
| | - Wilbert S Aronow
- Department of Cardiology, Westchester Medical Center, Valhalla, NY
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24
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Stewart AJ, Tuncay E, Pitt SJ, Rainbow RD. Editorial: Insulin resistance and cardiovascular disease. Front Endocrinol (Lausanne) 2023; 14:1266173. [PMID: 37600708 PMCID: PMC10436739 DOI: 10.3389/fendo.2023.1266173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 07/26/2023] [Indexed: 08/22/2023] Open
Affiliation(s)
- Alan J. Stewart
- School of Medicine, University of St Andrews, St Andrews, United Kingdom
| | - Erkan Tuncay
- Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Türkiye
| | - Samantha J. Pitt
- School of Medicine, University of St Andrews, St Andrews, United Kingdom
| | - Richard D. Rainbow
- Department of Cardiovascular and Metabolic Medicine & Liverpool Centre for Cardiovascular Sciences, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
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25
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Amalia M, Puteri MU, Saputri FC, Sauriasari R, Widyantoro B. Platelet Glycoprotein-Ib (GPIb) May Serve as a Bridge between Type 2 Diabetes Mellitus (T2DM) and Atherosclerosis, Making It a Potential Target for Antiplatelet Agents in T2DM Patients. Life (Basel) 2023; 13:1473. [PMID: 37511848 PMCID: PMC10381765 DOI: 10.3390/life13071473] [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: 05/29/2023] [Revised: 06/23/2023] [Accepted: 06/26/2023] [Indexed: 07/30/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a persistent metabolic condition that contributes to the development of cardiovascular diseases. Numerous studies have provided evidence that individuals with T2DM are at a greater risk of developing cardiovascular diseases, typically two to four times more likely than those without T2DM, mainly due to an increased risk of atherosclerosis. The rupture of an atherosclerotic plaque leading to pathological thrombosis is commonly recognized as a significant factor in advancing cardiovascular diseases caused by TD2M, with platelets inducing the impact of plaque rupture in established atherosclerosis and predisposing to the primary expansion of atherosclerosis. Studies suggest that individuals with T2DM have platelets that display higher baseline activation and reactivity than those without the condition. The expression enhancement of several platelet receptors is known to regulate platelet activation signaling, including platelet glycoprotein-Ib (GPIb). Furthermore, the high expression of platelet GP1b has been reported to increase the risk of platelet adhesion, platelet-leucocyte interaction, and thrombo-inflammatory pathology. However, the study exploring the role of GP1b in promoting platelet activation-induced cardiovascular diseases in T2DM patients is still limited. Therefore, we summarize the important findings regarding pathophysiological continuity between T2DM, platelet GPIb, and atherosclerosis and highlight the potential therapy targeting GPIb as a novel antiplatelet agent for preventing further cardiovascular incidents in TD2M patients.
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Affiliation(s)
- Muttia Amalia
- Doctoral Program, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok, Depok 16424, Indonesia
| | - Meidi Utami Puteri
- Laboratory of Pharmacology-Toxicology, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok, Depok 16424, Indonesia
| | - Fadlina Chany Saputri
- Laboratory of Pharmacology-Toxicology, Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok, Depok 16424, Indonesia
| | - Rani Sauriasari
- Faculty of Pharmacy, Universitas Indonesia, Kampus UI Depok, Depok 16424, Indonesia
| | - Bambang Widyantoro
- National Cardiovascular Center Harapan Kita, Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 11420, Indonesia
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26
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Sun W, Lin Y, Huang Y, Chan J, Terrillon S, Rosenbaum AI, Contrepois K. Robust and High-Throughput Analytical Flow Proteomics Analysis of Cynomolgus Monkey and Human Matrices with Zeno SWATH Data Independent Acquisition. Mol Cell Proteomics 2023:100562. [PMID: 37142056 DOI: 10.1016/j.mcpro.2023.100562] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 04/17/2023] [Accepted: 04/26/2023] [Indexed: 05/06/2023] Open
Abstract
Modern mass spectrometers routinely allow deep proteome coverage in a single experiment. These methods are typically operated at nano and micro flow regimes, but they often lack throughput and chromatographic robustness, which is critical for large-scale studies. In this context, we have developed, optimized and benchmarked LC-MS methods combining the robustness and throughput of analytical flow chromatography with the added sensitivity provided by the Zeno trap across a wide range of cynomolgus monkey and human matrices of interest for toxicological studies and clinical biomarker discovery. SWATH data independent acquisition (DIA) experiments with Zeno trap activated (Zeno SWATH DIA) provided a clear advantage over conventional SWATH DIA in all sample types tested with improved sensitivity, quantitative robustness and signal linearity as well as increased protein coverage by up to 9-fold. Using a 10-min gradient chromatography, up to 3,300 proteins were identified in tissues at 2 μg peptide load. Importantly, the performance gains with Zeno SWATH translated into better biological pathway representation and improved the ability to identify dysregulated proteins and pathways associated with two metabolic diseases in human plasma. Finally, we demonstrate that this method is highly stable over time with the acquisition of reliable data over the injection of 1,000+ samples (14.2 days of uninterrupted acquisition) without the need for human intervention or normalization. Altogether, Zeno SWATH DIA methodology allows fast, sensitive and robust proteomic workflows using analytical flow and is amenable to large-scale studies. This work provides detailed method performance assessment on a variety of relevant biological matrices and serves as a valuable resource for the proteomics community.
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Affiliation(s)
- Weiwen Sun
- Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, South San Francisco, CA 94080, USA
| | - Yuan Lin
- Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, South San Francisco, CA 94080, USA
| | - Yue Huang
- Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, South San Francisco, CA 94080, USA
| | - Josolyn Chan
- Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, South San Francisco, CA 94080, USA
| | - Sonia Terrillon
- Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, South San Francisco, CA 94080, USA
| | - Anton I Rosenbaum
- Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, South San Francisco, CA 94080, USA.
| | - Kévin Contrepois
- Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, South San Francisco, CA 94080, USA.
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27
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Yang Y, Wang Q, Li G, Guo W, Yang Z, Liu H, Deng X. Cysteine-Derived Chiral Carbon Quantum Dots: A Fibrinolytic Activity Regulator for Plasmin to Target the Human Islet Amyloid Polypeptide for Type 2 Diabetes Mellitus. ACS APPLIED MATERIALS & INTERFACES 2023; 15:2617-2629. [PMID: 36596222 DOI: 10.1021/acsami.2c17975] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
The fibrillization and deposition of the human islet amyloid polypeptide (hIAPP) are the pathological hallmark of type 2 diabetes mellitus (T2DM), and these insoluble fibrotic depositions of hIAPP are considered to strongly affect insulin secretion by inducing toxicity toward pancreatic islet β-cells. The current strategy of preventing amyloid aggregation by nanoparticle-assisted inhibitors can only disassemble fibrotic amyloids into more toxic oligomers and/or protofibrils. Herein, for the first time, we propose a type of cysteine-derived chiral carbon quantum dot (CQD) that targets plasmin, a core natural fibrinolytic protease in humans. These CQDs can serve as fibrinolytic activity regulators for plasmin to cleave hIAPP into nontoxic polypeptides or into even smaller amino acid fragments, thus alleviating hIAPP's fibrotic amyloid-induced cytotoxicity. Our experiments indicate that chiral CQDs have opposing effects on plasmin activity. The l-CQDs promote the cleavage of hIAPP by enhancing plasmin activity at a promotion ratio of 23.2%, thus protecting β-cells from amyloid-induced toxicity. In contrast, the resultant d-CQDs significantly inhibit proteolysis, decreasing plasmin activity by 31.5% under the same reaction conditions. Second harmonic generation (SHG) microscopic imaging is initially used to dynamically characterize hIAPP before and after proteolysis. The l-CQD promotion of plasmin activity thus provides a promising avenue for the hIAPP-targeted treatment of T2DM to treat low fibrinolytic activity, while the d-CQDs, as inhibitors of plasmin activity, may improve patient survival for hyperfibrinolytic conditions, such as those existing during surgeries and traumas.
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Affiliation(s)
- Yongzhen Yang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou510631, China
| | - Qin Wang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou510631, China
| | - Gongjian Li
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou510631, China
| | - Wenjing Guo
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou510530, China
| | - Zuojun Yang
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou510631, China
| | - Hao Liu
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou510631, China
| | - Xiaoyuan Deng
- MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou510631, China
- Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou510631, China
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28
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Fernández-González JF, García-Pedraza JÁ, Ordóñez JL, Terol-Úbeda AC, Martín ML, Morán A, García-Domingo M. Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT 1D Receptor Activation via NO Pathway. Int J Mol Sci 2023; 24:ijms24021378. [PMID: 36674892 PMCID: PMC9865738 DOI: 10.3390/ijms24021378] [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: 11/28/2022] [Revised: 12/24/2022] [Accepted: 12/28/2022] [Indexed: 01/13/2023] Open
Abstract
Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT1/5/7 agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT1D agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT1D antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT1D receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats.
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Affiliation(s)
- Juan Francisco Fernández-González
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - José Ángel García-Pedraza
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - José Luis Ordóñez
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - Anaïs Clara Terol-Úbeda
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
| | - María Luisa Martín
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - Asunción Morán
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
- Correspondence: ; Tel.: +34-663-18-24-55; Fax: +34-923-29-45-15
| | - Mónica García-Domingo
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
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Neves JS, Newman C, Bostrom JA, Buysschaert M, Newman JD, Medina JL, Goldberg IJ, Bergman M. Management of dyslipidemia and atherosclerotic cardiovascular risk in prediabetes. Diabetes Res Clin Pract 2022; 190:109980. [PMID: 35787415 DOI: 10.1016/j.diabres.2022.109980] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/26/2022] [Accepted: 06/29/2022] [Indexed: 11/03/2022]
Abstract
Prediabetes affects at least 1 in 3 adults in the U.S. and 1 in 5 in Europe. Although guidelines advocate aggressive management of lipid parameters in diabetes, most guidelines do not address treatment of dyslipidemia in prediabetes despite the increased atherosclerotic cardiovascular disease (ASCVD) risk. Several criteria are used to diagnose prediabetes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and HbA1c of 5.7-6.4%. Individuals with prediabetes have a greater risk of diabetes, a higher prevalence of dyslipidemia with a more atherogenic lipid profile and an increased risk of ASCVD. In addition to calculating ASCVD risk using traditional methods, an OGTT may further stratify risk. Those with 1-hour plasma glucose ≥8.6 mmol/L (155 mg/dL) and/or 2-hour ≥7.8 mmol/L (140 mg/dL) (IGT) have a greater risk of ASCVD. Diet and lifestyle modification are fundamental in prediabetes. Statins, ezetimibe and PCSK9 inhibitors are recommended in people requiring pharmacotherapy. Although high-intensity statins may increase risk of diabetes, this is acceptable because of the greater reduction of ASCVD. The LDL-C goal in prediabetes should be individualized. In those with IGT and/or elevated 1-hour plasma glucose, the same intensive approach to dyslipidemia as recommended for diabetes should be considered, particularly if other ASCVD risk factors are present.
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Affiliation(s)
- João Sérgio Neves
- Department of Endocrinology, Diabetes and Metabolism, São João University Hospital Center, Porto, Portugal; Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
| | - Connie Newman
- Division of Endocrinology, Diabetes and Metabolism, New York University Grossman School of Medicine, New York, NY, USA
| | - John A Bostrom
- Section of Cardiovascular Medicine, Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA
| | - Martin Buysschaert
- Department of Endocrinology and Diabetology, Université Catholique de Louvain, University Clinic Saint-Luc, Brussels, Belgium
| | - Jonathan D Newman
- Division of Cardiology and the Center for the Prevention of Cardiovascular Disease, New York University Grossman School of Medicine, New York, NY, USA
| | | | - Ira J Goldberg
- Division of Endocrinology, Diabetes and Metabolism, New York University Grossman School of Medicine, New York, NY, USA
| | - Michael Bergman
- Division of Endocrinology, Diabetes and Metabolism, New York University Grossman School of Medicine, New York, NY, USA; Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA
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Ebrahim H, Fiseha T, Ebrahim Y, Bisetegn H. Comparison of hematological parameters between type 2 diabetes mellitus patients and healthy controls at Dessie comprehensive specialized hospital, Northeast Ethiopia: Comparative cross-sectional study. PLoS One 2022; 17:e0272145. [PMID: 35895700 PMCID: PMC9328522 DOI: 10.1371/journal.pone.0272145] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 07/13/2022] [Indexed: 11/23/2022] Open
Abstract
Background Diabetes mellitus (DM) is a chronic condition associated with raised levels of blood glucose due to the body cannot produce any or enough insulin hormone or cannot be effectively utilized the produced insulin by the body. Patients with poorly controlled diabetes show a significant alteration in various parameters including metabolic, cellular, immunological, and hematological disturbances that leads to vascular complications. Thus, the main aim of this study is to compare hematological parameters between type 2 diabetes mellitus (T2DM) patients and healthy controls. Methods A comparative cross-sectional study was conducted in Dessie comprehensive specialized hospital from January to June 2021. A total of 240 study participants consisting of 120 T2DM patients and 120 healthy controls were recruited using a systematic random sampling technique. Hematological parameters were determined using the DIRUI BF6500 automated hematology analyzer. Independent T-test was used to compare the mean of hematological parameters between T2DM patients and healthy controls. Pearson correlation test was used to determine the correlation between FBG, BMI, SBP, DBP, and hematological parameters in T2DM patients. Multivariate logistic regression was used to assess the association between socio-demographic and clinical variables with anemia. The result was expressed in mean and standard deviation and presented in texts and tables. P-value < 0.05 was considered to be statistically significant. Results The mean and standard deviation of monocyte count, basophil count, monocyte %, basophil %, RBC count, hematocrit, MCV, MCH, RDW-SD, MPV, PDW, PLC-R, and plateletcrit showed a significant difference between T2DM patients and healthy control group. Pearson correlation coefficient showed that the total WBC count, neutrophil count, monocyte count, basophil count, RDW-CV, PDW, MPV, PLC-R, and plateletcrit were statistically positively correlated with FBG whereas RBC count, Hgb, hematocrit, MCV, MCH, and RDW-SD were statistically negatively correlated with FBG in T2DM patients. Moreover, total WBC count, neutrophil count, monocyte count, basophil count, Hgb, and plateletcrit were statistically positively correlated with BMI while RBC count, Hgb, hematocrit, MCV, MCH, and RDW-SD were statistically negatively correlated with BMI in T2DM patients. On the other hand, DBP was significantly positively correlated with platelet count and RDW-CV whereas SBP also significantly positively correlated with total WBC count, neutrophil count, basophil count, and PDW. Besides, DBP and SBP showed statistically significant negative correlations with RBC count, Hgb level, and Hct value in T2DM patients. The overall prevalence of anemia was 25.8% in T2DM patients with a higher prevalence of anemia (16.7%) in female patients. Multivariate logistic regression revealed that being non-employee worker (AOR: 3.6, 95% CI, 1.4–46.0, P = 0.002), presence of neuropathy (AOR: 13.40, 95% CI, 6.83–26.28, P = 0.00), and duration of the disease ≥ 5 years (AOR = 3.2, 95% CI, 1.2–15.3, P = 0.03) have had statistically significant association with anemia inT2DM patients. Conclusions Patients with T2DM may have significant alterations in various hematological parameters. Hematological parameters should be regularly tested for early diagnosis and proper management of diabetes-related complications.
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Affiliation(s)
- Hussen Ebrahim
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
- * E-mail:
| | - Temesgen Fiseha
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Yesuf Ebrahim
- Department of Medical Laboratory Sciences, Dessie Health Science College, Dessie, Ethiopia
| | - Habtye Bisetegn
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
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Fernández-González JF, García-Pedraza JÁ, Marín-Quílez A, Bastida JM, Martín ML, Morán A, García-Domingo M. Effect of sarpogrelate treatment on 5-HT modulation of vascular sympathetic innervation and platelet activity in diabetic rats. Biomed Pharmacother 2022; 153:113276. [PMID: 35717784 DOI: 10.1016/j.biopha.2022.113276] [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: 04/19/2022] [Revised: 05/26/2022] [Accepted: 06/08/2022] [Indexed: 11/16/2022] Open
Abstract
This study aimed to investigate whether the 5-HT2 receptor blockade alters the 5-HT effect on vascular sympathetic neurotransmission and platelet activation in type 1 diabetes. 28-day diabetes was obtained by alloxan (150 mg/kg; s.c.) in male Wistar rats, administering sarpogrelate (5-HT2 blocker; 30 mg/kg/day; p.o.) for 14 days. Blood glucose and body weight were monitored for 28 days. After 4 weeks of diabetes induction, food and drink intake, urine, plasma-platelet 5-HT, and platelet activation were determined in normoglycemic, non-treated diabetic and sarpogrelate-treated diabetic rats. Another set of diabetic rats were pithed to run the vascular sympathetic stimulation or exogenous noradrenaline administration, examining the induced vasoconstrictor responses. Sarpogrelate treatment significantly reduced drink intake and urine, whereas BW gain, hyperglycemia, and food intake were not modified in diabetic rats. The platelet activation and plasma 5-HT concentration were decreased (increasing the stored 5-HT platelet) by 5-HT2 blockade in diabetic animals. The sympathetic-induced vasoconstrictions were higher in non-treated than in sarpogrelate-treated diabetic rats. 5-HT inhibited these vasopressor responses, reproduced exclusively by the 5-HT1/5/7 receptor agonist, 5-CT. The 5-CT-produced inhibition was partly reversed by 5-HT1D or 5-HT7 antagonists (LY310762 or SB-258719, respectively), and totally annulled by the mixture of LY310762+SB-258719. Noradrenaline-caused vasoconstrictions were also decreased by 5-CT. In conclusion, our results reveal that 14-day sarpogrelate treatment improves polydipsia and polyuria, reduces platelet hyperactivation, plasma 5-HT and the vascular sympathetic tone, and changes 5-HT receptors inhibiting noradrenergic drive in diabetic rats: pre and/or postjunctional 5-HT1D/7 are involved in the sympatho-inhibition.
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Affiliation(s)
- Juan Francisco Fernández-González
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - José Ángel García-Pedraza
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - Ana Marín-Quílez
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain; Departamento de Hematología, Complejo Asistencial Universitario de Salamanca (CAUSA), 37007 Salamanca, Spain
| | - José María Bastida
- Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain; Departamento de Hematología, Complejo Asistencial Universitario de Salamanca (CAUSA), 37007 Salamanca, Spain
| | - María Luisa Martín
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - Asunción Morán
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain
| | - Mónica García-Domingo
- Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo San Vicente 58-182, 37007 Salamanca, Spain.
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Alsharidah AS. Diabetes mellitus and diabetic nephropathy: a review of the literature on hemostatic changes in coagulation and thrombosis. Blood Res 2022; 57:101-105. [PMID: 35620906 PMCID: PMC9242838 DOI: 10.5045/br.2022.2021204] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 01/31/2022] [Accepted: 03/14/2022] [Indexed: 11/17/2022] Open
Abstract
Vascular complications lead to morbidity and mortality in patients with diabetes. Diabetic nephropathy (DN) is one of the main life-threatening problems for these patients, as it is the main cause of end-stage renal disease. This study aimed to measure the clinical effects of diabetes in patients with diabetes and in patients with diabetic nephropathy. Improved hypoglycemic control in patients with diabetes could impressively reduce platelet hyperreactivity, and oxidative stress alters the levels of many coagulation and thrombosis factors, resulting in an abnormal hemostasis and impaired levels of numerous serum markers. Most studies have revealed that coagulation factor levels are high in patients with diabetes and nephrodiabetes. Serum inflammatory factors, and coagulation and endothelial functions are good predictors of diabetic nephropathy. This literature review was conducted with access to scholarly databases and Google Scholar through Qassim University, and it analyzes studies from early 2010 until November 2020. Many studies have inferred that diabetes severely affects hemostasis and increases the risk of cardiovascular disease.
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Affiliation(s)
- Ashwag S Alsharidah
- Department of Physiology, College of Medicine, Qassim University, Buraidah, Saudi Arabia
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33
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Kandregula B, Narisepalli S, Chitkara D, Mittal A. Exploration of Lipid-Based Nanocarriers as Drug Delivery Systems in Diabetic Foot Ulcer. Mol Pharm 2022; 19:1977-1998. [PMID: 35481377 DOI: 10.1021/acs.molpharmaceut.1c00970] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Diabetes mellitus is a chronic manifestation characterized by high levels of glucose in the blood resulting in several complications including diabetic wounds and ulcers, which predominantly require a longer duration of treatment and adversely affect the quality of life of the patients. Nanotechnology-based therapeutics (both intrinsic and extrinsic types) have emerged as a promising treatment in diabetic foot ulcer/chronic wounds owing to their unique characteristics and specific functional properties. In this review, we have focused on the significance of the use of lipids in the healing of diabetic ulcers, their interaction with the injured skin, and recent trends in lipid-based nanocarriers for the healing of diabetic wounds. Lipid nanocarriers are also being investigated for gene therapy in diabetic wound healing to encapsulate nucleic acids such as siRNA and miRNA, which could silence the expression of inflammatory cytokines overexpressed in chronic wounds. Additionally, these are also being explored for encapsulating proteins, peptides, growth factors, and other biological genetic material as therapeutic agents. Lipid-based nanocarriers encompassing a wide variety of carriers such as liposomes, niosomes, ethosomes, solid lipid nanoparticles, and lipidoid nanoparticles that are explored for the treatment of foot ulcers supplemented with relevant research studies have been discussed in the present review. Lipid-based nanodrug delivery systems have demonstrated promising wound healing potential, particularly in diabetic conditions due to the enhanced efficacy of the entrapped active molecules.
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Affiliation(s)
- Bhaskar Kandregula
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India
| | - Saibhargav Narisepalli
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India
| | - Deepak Chitkara
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India
| | - Anupama Mittal
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.,Department of Cellular and Molecular Biology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
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Zajda A, Sikora J, Huttunen KM, Markowicz-Piasecka M. Structural Comparison of Sulfonamide-Based Derivatives That Can Improve Anti-Coagulation Properties of Metformin. Int J Mol Sci 2022; 23:ijms23084132. [PMID: 35456961 PMCID: PMC9029893 DOI: 10.3390/ijms23084132] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 04/02/2022] [Accepted: 04/06/2022] [Indexed: 01/13/2023] Open
Abstract
Due to its high efficiency, good safety profile, and potential cardio-protective properties, metformin, a dimethyl biguanide, is the first-line medication in antihyperglycemic treatment for type 2 diabetic patients. The aim of our present study was to assess the effects of eight new sulfonamide-based derivatives of metformin on selected plasma parameters and vascular hemostasis, as well as on endothelial and smooth muscle cell function. The compounds with an alkyl chain (1–3), trifluoromethyl substituent (4), or acetyl group (5) significantly elevated glucose utilization in human umbilical endothelial cells (HUVECs), similarly to metformin. Our novel findings showed that metformin analogues 1–3 presented the most beneficial properties because of their greatest safety profile in the WST-1 cell viability assay, which was also proved in the further HUVEC integrity studies using RTCA DP. Compounds 1–3 did not affect either HUVEC or aortal smooth muscle cell (AoSMC) viability up to 3.0 mM. Importantly, these compounds beneficially affected some of the coagulation parameters, including factor X and antithrombin III activity. In contrast to the above-mentioned metformin analogues, derivatives 4 and 5 exerted more profound anticoagulation effects; however, they were also more cytotoxic towards HUVECs, as IC50 values were 1.0–1.5 mM. In conclusion, the chemical modification of a metformin scaffold into sulfonamides possessing alkyl substituents results in the formation of novel derivatives with potential bi-directional activity including anti-hyperglycemic properties and highly desirable anti-coagulant activity.
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Affiliation(s)
- Agnieszka Zajda
- Laboratory of Bioanalysis, Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego1, 90-151 Lodz, Poland;
| | - Joanna Sikora
- Department of Bioinorganic Chemistry, Medical University of Lodz, ul. Muszyńskiego1, 90-151 Lodz, Poland;
| | - Kristiina M. Huttunen
- School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, P.O. Box 1627, 70211 Kuopio, Finland;
| | - Magdalena Markowicz-Piasecka
- Laboratory of Bioanalysis, Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Medical University of Lodz, ul. Muszyńskiego1, 90-151 Lodz, Poland;
- Correspondence: ; Tel.: +48-42-677-92-50
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Zhang Y, Zhou H. Hyper-reactive platelets and type 2 diabetes. ZHONG NAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF CENTRAL SOUTH UNIVERSITY. MEDICAL SCIENCES 2022; 47:374-383. [PMID: 35545331 PMCID: PMC10930063 DOI: 10.11817/j.issn.1672-7347.2022.210271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Indexed: 06/15/2023]
Abstract
Type 2 diabetes mellitus is a progressive process. With the course of the disease progress, microvascular and macrovascular complications always happen. Thrombotic events caused by macrovascular complications, including coronary heart diseases and cerebrovascular diseases, are the main fatal factor for the patients with type 2 diabetes. Endothelial dysfunction, coagulative activation, impaired fibrinolysis, together with hyper-reactive platelets contribute to the diabetic prothrombotic state, which is strongly related to the macrovascular complications. In particular, the hyper-reactive platelets play a fundamental role among them. Type 2 diabetes is characterized by several metabolic dysfunctions such as hyperglycemia, insulin resistance and shortage, oxidative stress, systemic inflammation, obesity, and dyslipidemia. These metabolic dysfunctions work together to promote the formation of hyper-reactive platelets, which are distinctive in type 2 diabetes. The regular antiplatelet drugs, like aspirin, show limited inhibitory effect on them. Hence, studying the mechanism behind the hyper-reactive platelets could provide a brand-new view on the prevention of macrovascular complications and cardiovascular events in type 2 diabetes.
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Affiliation(s)
- Yi Zhang
- Department of Endocrinology, People's Hospital of Nanchuan, Chongqing 408400, China.
| | - Huamei Zhou
- Department of Endocrinology, People's Hospital of Nanchuan, Chongqing 408400, China.
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Milczak A, Winiarczyk D, Winiarczyk S, Bochyńska D, Adaszek Ł, Winiarczyk M, Lechowski R. Procoagulant and anticoagulant plasma indicators in diabetic dogs showing increased antithrombin III levels in canine diabetes mellitus. BMC Vet Res 2022; 18:108. [PMID: 35305618 PMCID: PMC8933892 DOI: 10.1186/s12917-022-03179-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 02/07/2022] [Indexed: 11/19/2022] Open
Abstract
Background Diabetes mellitus (DM) often leads to dangerous thromboembolic complications in humans. DM is also a relatively common endocrinopathy of dogs. There is scarce information regarding procoagulant and anticoagulant plasma indicators in this disease. The aim of the study was to evaluate the levels of the selected plasma haemostatic parameters in dogs suffering from diabetes. The study group consisted of 20 dogs meeting all the inclusion criteria, with fasting glycaemia exceeding 11.1 mmol/l. The control group consisted of 15 healthy dogs presented for routine examination. An evaluation of the prothrombin time (PT); and fibrinogen, D-dimer and antithrombin III (ATIII) levels was performed. Results Except for ATIII activity, the haemostatic parameter differences were not statistically significant. High values of ATIII activity were observed in 90% of diabetic dogs. On average, the values amounted to 166.6% and were 31.4% higher than those in the control group. The ATIII activity in the diabetic group was significantly higher than that in the control group (p = 0.0004). Conclusions Here, we report elevated levels of ATIII in diabetic dogs. This finding may suggest the protective role of ATIII against potential thrombotic events. However, the exact role of ATIII in dog diabetes remains unclear.
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An Observational Study on Patients with Acute Limb Ischemia and SARS-CoV-2 Infection: Early and Late Results in Limb Salvage Rate. J Clin Med 2021; 10:jcm10215083. [PMID: 34768611 PMCID: PMC8584433 DOI: 10.3390/jcm10215083] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 10/26/2021] [Accepted: 10/26/2021] [Indexed: 01/08/2023] Open
Abstract
An observational study on 22 patients presenting with acute limb ischemia and SARS-CoV-2 infection, and without any other embolic risk factors, was performed. All patients were classified according to Rutherford classification for acute limb ischemia. The primary goal of this study was to assess the risk of amputation in these patients after revascularization procedures. The secondary goal was to find the correlation between acute limb ischemia (ALI) severity, patient comorbidities, risk of death, and the association of SARS-CoV-2 infection. The patients were treated by open surgery (18 patients—81.81%) or by the means of endovascular techniques (four patients—18.18%). The amputation-free survival rate was 81.81% in hospital and 86.36% at 1-month follow-up. In this study, the presence of SARS-CoV-2 infection did not influence the amputation-free survival rate: it was only the risk factor for the arterial thrombosis and the trigger for the acute ischemic event. The application of the standard treatment—open surgery or endovascular revascularization—in patients with acute limb ischemia and SARS-CoV-2 infection represents the key to success for lower limb salvage.
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Lim HY, Lui B, Tacey M, Kwok A, Varadarajan S, Donnan G, Nandurkar H, Ho P. Global coagulation assays in patients with diabetes mellitus. Res Pract Thromb Haemost 2021; 5:e12611. [PMID: 34765860 PMCID: PMC8576266 DOI: 10.1002/rth2.12611] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 09/28/2021] [Accepted: 10/08/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND There is significant heterogeneity in the incidence and severity of diabetes-associated vascular complications and there is no routine biomarker that accurately predicts these outcomes. This pilot study investigates the role of global coagulation assays in patients with diabetes mellitus. METHODS In this cross-sectional study, patients with diabetes not on anticoagulation or dialysis and without active malignancy were recruited from endocrinology clinics. Blood samples were collected for global coagulation assays including thromboelastography (TEG), thrombin generation using calibrated automated thrombogram (CAT), and fibrin generation and fibrinolysis using the overall hemostatic potential (OHP) assay. The results were compared with healthy controls. RESULTS A total of 147 adult patients including 19 with type 1 diabetes (T1DM), 120 with type 2 diabetes (T2DM), and eight with latent autoimmune diabetes were recruited. Compared with 153 healthy controls, patients with diabetes demonstrated higher maximum amplitude (68.6 vs 60.2 mm, p < 0.001) on TEG, and higher OHP (9.3 vs 6.4, p < 0.001) with comparable CAT parameters. Patients with T2DM were more hypercoagulable than those with T1DM on most biomarkers. Higher maximum amplitude, velocity index, and OHP were associated with increased risk of complications (C-stat 0.82). Patients with history of microvascular complications appear to have more hypercoagulable thrombin and fibrin generation than those without. CONCLUSION Patients with diabetes have more hypercoagulable profiles on global coagulation assays, particularly patients with T2DM and those with microvascular complications. Further studies with longitudinal follow-up are ongoing to evaluate the utility of global coagulation assays in predicting long-term patient outcomes.
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Affiliation(s)
- Hui Yin Lim
- Department of HematologyNorthern Pathology VictoriaNorthern HospitalEppingVic.Australia
- Australian Centre for Blood DiseasesMonash UniversityMelbourneVic.Australia
- Department of MedicineNorthern HealthUniversity of MelbourneHeidelbergVic.Australia
| | - Brandon Lui
- Department of HematologyNorthern Pathology VictoriaNorthern HospitalEppingVic.Australia
| | - Mark Tacey
- Office of ResearchNorthern Centre for Health Education and ResearchNorthern HealthEppingVic.Australia
- Melbourne School of Population and Global HealthUniversity of MelbourneCarltonVic.Australia
| | - Anna Kwok
- Department of HematologyNorthern Pathology VictoriaNorthern HospitalEppingVic.Australia
| | | | - Geoffrey Donnan
- The Melbourne Brain CentreRoyal Melbourne HospitalUniversity of MelbourneParkvilleVic.Australia
| | - Harshal Nandurkar
- Australian Centre for Blood DiseasesMonash UniversityMelbourneVic.Australia
| | - Prahlad Ho
- Department of HematologyNorthern Pathology VictoriaNorthern HospitalEppingVic.Australia
- Australian Centre for Blood DiseasesMonash UniversityMelbourneVic.Australia
- Department of MedicineNorthern HealthUniversity of MelbourneHeidelbergVic.Australia
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Bryk-Wiązania AH, Undas A. Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation. Cardiovasc Diabetol 2021; 20:191. [PMID: 34551784 PMCID: PMC8459566 DOI: 10.1186/s12933-021-01372-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 08/25/2021] [Indexed: 12/19/2022] Open
Abstract
A prothrombotic state is a typical feature of type 2 diabetes mellitus (T2DM). Apart from increased platelet reactivity, endothelial dysfunction, hyperfibrinogenemia, and hypofibrinolysis are observed in T2DM. A variety of poorly elucidated mechanisms behind impaired fibrinolysis in this disease have been reported, indicating complex associations between platelet activation, fibrin formation and clot structure, and fibrinolysis inhibitors, in particular, elevated plasminogen antigen inhibitor-1 levels which are closely associated with obesity. Abnormal fibrin clot structure is of paramount importance for relative resistance to plasmin-mediated lysis in T2DM. Enhanced thrombin generation, a proinflammatory state, increased release of neutrophil extracellular traps, elevated complement C3, along with posttranslational modifications of fibrinogen and plasminogen have been regarded to contribute to altered clot structure and impaired fibrinolysis in T2DM. Antidiabetic agents such as metformin and insulin, as well as antithrombotic agents, including anticoagulants, have been reported to improve fibrin properties and accelerate fibrinolysis in T2DM. Notably, recent evidence shows that hypofibrinolysis, assessed in plasma-based assays, has a predictive value in terms of cardiovascular events and cardiovascular mortality in T2DM patients. This review presents the current data on the mechanisms underlying arterial and venous thrombotic complications in T2DM patients, with an emphasis on hypofibrinolysis and its impact on clinical outcomes. We also discuss potential modulators of fibrinolysis in the search for optimal therapy in diabetic patients.
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Affiliation(s)
- Agata Hanna Bryk-Wiązania
- Department of Endocrinology, Jagiellonian University Medical College, Kraków, Poland.,University Hospital, Kraków, Poland
| | - Anetta Undas
- Institute of Cardiology, Jagiellonian University Medical College, 80 Prądnicka St., 31-202, Kraków, Poland. .,John Paul II Hospital, Kraków , Poland.
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Hierons SJ, Marsh JS, Wu D, Blindauer CA, Stewart AJ. The Interplay between Non-Esterified Fatty Acids and Plasma Zinc and Its Influence on Thrombotic Risk in Obesity and Type 2 Diabetes. Int J Mol Sci 2021; 22:ijms221810140. [PMID: 34576303 PMCID: PMC8471329 DOI: 10.3390/ijms221810140] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/13/2021] [Accepted: 09/16/2021] [Indexed: 12/29/2022] Open
Abstract
Thrombosis is a major comorbidity of obesity and type-2 diabetes mellitus (T2DM). Despite the development of numerous effective treatments and preventative strategies to address thrombotic disease in such individuals, the incidence of thrombotic complications remains high. This suggests that not all the pathophysiological mechanisms underlying these events have been identified or targeted. Non-esterified fatty acids (NEFAs) are increasingly regarded as a nexus between obesity, insulin resistance, and vascular disease. Notably, plasma NEFA levels are consistently elevated in obesity and T2DM and may impact hemostasis in several ways. A potentially unrecognized route of NEFA-mediated thrombotic activity is their ability to disturb Zn2+ speciation in the plasma. Zn2+ is a potent regulator of coagulation and its availability in the plasma is monitored carefully through buffering by human serum albumin (HSA). The binding of long-chain NEFAs such as palmitate and stearate, however, trigger a conformational change in HSA that reduces its ability to bind Zn2+, thus increasing the ion’s availability to bind and activate coagulation proteins. NEFA-mediated perturbation of HSA-Zn2+ binding is thus predicted to contribute to the prothrombotic milieu in obesity and T2DM, representing a novel targetable disease mechanism in these disorders.
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Affiliation(s)
- Stephen J. Hierons
- School of Medicine, University of St. Andrews, St. Andrews KY16 9TF, Fife, UK; (S.J.H.); (J.S.M.); (D.W.)
| | - Jordan S. Marsh
- School of Medicine, University of St. Andrews, St. Andrews KY16 9TF, Fife, UK; (S.J.H.); (J.S.M.); (D.W.)
| | - Dongmei Wu
- School of Medicine, University of St. Andrews, St. Andrews KY16 9TF, Fife, UK; (S.J.H.); (J.S.M.); (D.W.)
| | | | - Alan J. Stewart
- School of Medicine, University of St. Andrews, St. Andrews KY16 9TF, Fife, UK; (S.J.H.); (J.S.M.); (D.W.)
- Correspondence: ; Tel.: +44-(0)-1334-463546; Fax: +44-(0)-1334-463482
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Ceriello A, Prattichizzo F. Pharmacological management of COVID-19 in type 2 diabetes. J Diabetes Complications 2021; 35:107927. [PMID: 33896714 PMCID: PMC8052602 DOI: 10.1016/j.jdiacomp.2021.107927] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/08/2021] [Accepted: 04/08/2021] [Indexed: 01/08/2023]
Abstract
Evidence suggests that diabetes is one the most relevant comorbidity in affecting the prognosis of COVID-19. Albeit there are no specific trials nor subgroup analysis showing the effect of COVID-19 therapies in patients with diabetes, selected features of this disease and the side effects associated with certain drugs require a proper knowledge to optimize the pharmacological therapy of patients with diabetes and COVID-19. While chronic anti-hypertensive and glucose-lowering therapies should not be discontinued nor preferred for preventive purposes, the low-grade pro-inflammatory, the thrombosis-prone status of diabetes, the role of acute hyperglycaemia in promoting adverse outcomes in patients admitted to ICU, and the observed increased mortality in patients with poor long-term glycaemic control delineate a delicate balance in case of severe forms of COVID-19. Here, we briefly summarized some of the key pharmacological issues linked to the management of patients with diabetes and COVID-19, in order to provide indications to minimize the deleterious effects of the concomitant presentation of these diseases and to use the existing pharmacological options in an appropriate manner.
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Johansson M, Eriksson AC, Östgren CJ, Whiss PA. Platelet adhesion in type 2 diabetes: impact of plasma albumin and mean platelet volume. Thromb J 2021; 19:40. [PMID: 34078390 PMCID: PMC8173756 DOI: 10.1186/s12959-021-00291-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 05/17/2021] [Indexed: 12/31/2022] Open
Abstract
Background Altered mean platelet volume (MPV) and plasma albumin has been reported in type 2 diabetes (T2D). MPV is suggested to predict cardiovascular risk but there is a lack of evidence for associations between MPV and platelet adhesion. Plasma albumin and magnesium are other factors reported to influence thrombotic risk. The objectives of this study were to assess the association between platelet adhesion and plasma factors with a potential role to affect platelet activation. Methods Blood was collected from 60 T2D patients and 60 healthy controls. Platelet adhesion to different protein surfaces induced by various soluble activators were measured in microplates. MPV, albumin and magnesium were analysed together with additional routine tests. Results Despite normal levels, plasma albumin significantly correlated with adhesion of T2D platelets but not with controls. There was a significant association between MPV and platelet adhesion in both groups, but association was smaller in T2D. Levels of glucose, HbA1c or magnesium did not correlate with platelet adhesion. Conclusions Plasma albumin was associated with platelet adhesion in T2D suggesting that albumin may be a factor to consider upon cardiovascular risk assessment. MPV was more associated with the level of platelet adhesion in healthy individuals than in well-controlled T2D patients.
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Affiliation(s)
- Mona Johansson
- Department of Biomedical and Clinical Sciences (BKV), Division of Clinical Chemistry and Pharmacology, Linköping University, Building 420, Entrance 68, Level 8, Campus US, SE-581 83, Linköping, Sweden
| | - Andreas C Eriksson
- Department of Biomedical and Clinical Sciences (BKV), Division of Clinical Chemistry and Pharmacology, Linköping University, Building 420, Entrance 68, Level 8, Campus US, SE-581 83, Linköping, Sweden
| | - Carl Johan Östgren
- Department of Health, Medicine and Caring Sciences (HMV), Division of Prevention, Rehabilitation and Community Medicine, Linköping University, SE-581 83, Linköping, Sweden
| | - Per A Whiss
- Department of Biomedical and Clinical Sciences (BKV), Division of Clinical Chemistry and Pharmacology, Linköping University, Building 420, Entrance 68, Level 8, Campus US, SE-581 83, Linköping, Sweden.
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Aleman MN, Díaz EI, Luciardi MC, Mariani AC, Bazán MC, Abregu AV. Hemostatic state of children with type 1 diabetes. Ann Pediatr Endocrinol Metab 2021; 26:99-104. [PMID: 34218631 PMCID: PMC8255861 DOI: 10.6065/apem.2040142.071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 09/28/2020] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Hyperglycemia is one of the factors responsible for the molecular alterations that modify hemostasis. The aim of this study was to determine the levels of circulating molecules that have a prothrombotic impact on the child and adolescent population with type 1 diabetes mellitus. METHODS There were 35 patients with type 1 diabetes mellitus (11.0±2.5 years of age and a median 3.7±2.0 years of the disease) with no vascular complications and 20 healthy controls with similar age, sex, and body mass index included in the study. The evaluated parameters were fibrinogen, plasminogen activator inhibitor-1 (PAI1), von Willebrand factor antigen, and standard coagulation tests (platelet count, prothrombin time, and activated partial thromboplastin time). Glycemic control was evaluated by hemoglobin A1c and fasting blood glucose tests, and the presence of retinopathy and nephropathy was ruled out. The data obtained were analyzed by IBM SPSS Statistics ver. 20.0 and expressed as mean±standard deviation. The Pearson correlation coefficient was applied to investigate correlations between variables. RESULTS Diabetic patients showed significantly higher levels of fibrinogen (308±66 mg/dL vs. 246±18 mg/dL, P=0.0001), PAI-1 (41.6±12 ng/mL vs. 11.7±1.0 ng/mL, P=0.0001), and von Willebrand factor antigen (284%±55% vs. 121%±19%, P=0.0001). However, standard coagulation tests did not show differences between the 2 groups. PAI-1 was correlated with glycemia, hemoglobin A1c, fibrinogen, and von Willebrand factor antigen. CONCLUSION Elevated levels of fibrinogen, PAI-1, and von Willebrand factor antigen were found in the pediatric and adolescent population with type 1 diabetes mellitus, which suggests a prothrombotic state.
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Affiliation(s)
- Mariano Nicolás Aleman
- Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Tucumán, Argentina,Address for correspondence: Mariano Nicolás Áleman Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Balcarce 747, San Miguel de Tucumán, Tucumán 4000, Argentina
| | - Elba Irma Díaz
- Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Maria Constanza Luciardi
- Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Ana Carolina Mariani
- Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Maria Cristina Bazán
- Departamento de Endocrinología, Hospital del Niño Jesús de Tucumán, Tucumán, Argentina
| | - Adela Victoria Abregu
- Departamento de Bioquímica Aplicada, Facultad de Bioquímica, Universidad Nacional de Tucumán, Tucumán, Argentina
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Kountouri A, Korakas E, Ikonomidis I, Raptis A, Tentolouris N, Dimitriadis G, Lambadiari V. Type 1 Diabetes Mellitus in the SARS-CoV-2 Pandemic: Oxidative Stress as a Major Pathophysiological Mechanism Linked to Adverse Clinical Outcomes. Antioxidants (Basel) 2021; 10:752. [PMID: 34065123 PMCID: PMC8151267 DOI: 10.3390/antiox10050752] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 04/29/2021] [Accepted: 05/03/2021] [Indexed: 01/08/2023] Open
Abstract
Recent reports have demonstrated the association between type 1 diabetes mellitus (T1DM) and increased morbidity and mortality rates during coronavirus disease (COVID-19) infection, setting a priority of these patients for vaccination. Impaired innate and adaptive immunity observed in T1DM seem to play a major role. Severe, life-threatening COVID-19 disease is characterized by the excessive release of pro-inflammatory cytokines, known as a "cytokine storm". Patients with T1DM present elevated levels of cytokines including interleukin-1a (IL), IL-1β, IL-2, IL-6 and tumor necrosis factor alpha (TNF-α), suggesting the pre-existence of chronic inflammation, which, in turn, has been considered the major risk factor of adverse COVID-19 outcomes in many cohorts. Even more importantly, oxidative stress is a key player in COVID-19 pathogenesis and determines disease severity. It is well-known that extreme glucose excursions, the prominent feature of T1DM, are a potent mediator of oxidative stress through several pathways including the activation of protein kinase C (PKC) and the increased production of advanced glycation end products (AGEs). Additionally, chronic endothelial dysfunction and the hypercoagulant state observed in T1DM, in combination with the direct damage of endothelial cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may result in endothelial and microcirculation impairment, which contribute to the pathogenesis of acute respiratory syndrome and multi-organ failure. The binding of SARS-CoV-2 to angiotensin converting enzyme 2 (ACE2) receptors in pancreatic b-cells permits the direct destruction of b-cells, which contributes to the development of new-onset diabetes and the induction of diabetic ketoacidosis (DKA) in patients with T1DM. Large clinical studies are required to clarify the exact pathways through which T1DM results in worse COVID-19 outcomes.
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Affiliation(s)
- Aikaterini Kountouri
- Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (A.K.); (E.K.); (A.R.)
| | - Emmanouil Korakas
- Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (A.K.); (E.K.); (A.R.)
| | - Ignatios Ikonomidis
- Second Cardiology Department, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Athanasios Raptis
- Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (A.K.); (E.K.); (A.R.)
| | - Nikolaos Tentolouris
- First Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece;
| | - George Dimitriadis
- Sector of Medicine, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Vaia Lambadiari
- Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; (A.K.); (E.K.); (A.R.)
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Marcinczyk N, Gołaszewska A, Gromotowicz-Poplawska A, Misztal T, Strawa J, Tomczyk M, Kasacka I, Chabielska E. Multidirectional Effects of Tormentil Extract on Hemostasis in Experimental Diabetes. Front Pharmacol 2021; 12:682987. [PMID: 34025439 PMCID: PMC8131833 DOI: 10.3389/fphar.2021.682987] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 04/21/2021] [Indexed: 12/24/2022] Open
Abstract
In our previous study, we showed that ellagitannin- and procyanidin-rich tormentil extract (TE) decreased experimental arterial thrombosis in normoglycemic rats through platelet inhibition. TE also slightly increased coagulation and attenuated fibrinolysis; however, these effects did not nullify the antithrombotic effect of TE. The present study aimed to assess whether TE exerts antithrombotic activity in streptozotocin (STZ)-induced diabetes, which is characterized by pre-existing increased coagulation and impaired fibrinolysis, in vivo and ex vivo thrombosis assays. TE (100, 200, or 400 mg/kg, p. o.) was administered for 14 days to STZ-induced diabetic rats and mice. TE at 100 mg/kg dose decreased the thrombus area in the mice model of laser-induced thrombosis through its potent antiplatelet effect. However, TE at 200 mg/kg dose increased thrombus weight in electrically induced arterial thrombosis in rats. The prothrombotic effect could be due to increased coagulation and attenuated fibrinolysis. TE at 400 mg/kg dose also improved vascular functions, which was mainly reflected as an increase in the arterial blood flow, bleeding time prolongation, and thickening of the arterial wall. However, TE at 400 mg/kg dose did not exert antithrombotic effect. Summarizing, the present results show that TE may exert multidirectional effects on hemostasis in STZ-induced diabetic rats and mice. TE inhibited platelet activity and improved endothelial functions, but it also showed unfavorable effects by increasing the activity of the coagulation system and by inhibiting fibrinolysis. These contrasting effects could be the reason for model-specific influence of TE on the thrombotic process in STZ-induced diabetes.
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Affiliation(s)
- Natalia Marcinczyk
- Department of Biopharmacy, Medical University of Bialystok, Bialystok, Poland
| | - Agata Gołaszewska
- Department of Physical Chemistry, Medical University of Bialystok, Bialystok, Poland
| | | | - Tomasz Misztal
- Department of Physical Chemistry, Medical University of Bialystok, Bialystok, Poland
| | - Jakub Strawa
- Department of Pharmacognosy, Medical University of Bialystok, Bialystok, Poland
| | - Michał Tomczyk
- Department of Pharmacognosy, Medical University of Bialystok, Bialystok, Poland
| | - Irena Kasacka
- Department of Histology and Cytophysiology, Medical University of Bialystok, Bialystok, Poland
| | - Ewa Chabielska
- Department of Biopharmacy, Medical University of Bialystok, Bialystok, Poland
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Hinton W, Nemeth B, de Lusignan S, Field B, Feher MD, Munro N, Roberts LN, Arya R, Whyte MB. Effect of type 1 diabetes and type 2 diabetes on the risk of venous thromboembolism. Diabet Med 2021; 38:e14452. [PMID: 33165941 PMCID: PMC8247424 DOI: 10.1111/dme.14452] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 10/28/2020] [Accepted: 10/29/2020] [Indexed: 12/12/2022]
Abstract
AIMS Whether diabetes increases venous thromboembolism (VTE) is unclear. Any greater risk may relate to insulin resistance, but many studies did not differentiate between type 1 diabetes and type 2 diabetes for VTE risk. METHODS Retrospective cohort study of the Royal College of General Practitioners Research and Surveillance Centre, comprising over 530 primary care practices. We determined whether type 1 diabetes and/or type 2 diabetes are independent risk factors for VTE. The index date was 1 January 2009, individuals were followed to 31 December 2018, or censoring. Cox proportional hazard regression analysis was used to investigate the risk of VTE in people with type 1 diabetes and type 2 diabetes relative to no diabetes. The primary outcome was occurrence of VTE. The model was adjusted for potential confounders for VTE. RESULTS There were 7086 people with type 1 diabetes and 95,566 with type 2 diabetes, diagnosed before 1 January 2009. The non-diabetes group consisted of 1,407,699 people. In the unadjusted analysis, there was no increased risk of VTE with type 1 diabetes (HR 1.00, 95% CI 0.76-1.33) but there was for type 2 diabetes (HR 2.70, 95% CI 2.57-2.84). In the fully adjusted model, VTE risk was increased in type 1 diabetes (HR 1.46, 95% CI 1.11-1.92), but not with type 2 diabetes (HR 1.06, 95% CI 0.98-1.14). CONCLUSIONS Type 1 diabetes was associated with a greater risk for VTE while type 2 diabetes was not. Further work is needed to determine the reason(s) for this.
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Affiliation(s)
- William Hinton
- Nuffield Department of Primary Care Health SciencesUniversity of OxfordOxfordUK
| | - Banne Nemeth
- Department of Clinical EpidemiologyLeiden UniversityLeidenThe Netherlands
| | - Simon de Lusignan
- Nuffield Department of Primary Care Health SciencesUniversity of OxfordOxfordUK
- Faculty of Health & Medical SciencesUniversity of SurreyGuildfordSurreyUK
- Royal College of General PractitionersRoyal College of General Practitioners (RCGP) Research and Surveillance Centre (RSCLondonUK
| | - Ben Field
- Faculty of Health & Medical SciencesUniversity of SurreyGuildfordSurreyUK
| | - Michael D. Feher
- Nuffield Department of Primary Care Health SciencesUniversity of OxfordOxfordUK
| | - Neil Munro
- Faculty of Health & Medical SciencesUniversity of SurreyGuildfordSurreyUK
| | - Lara N. Roberts
- King’s Thrombosis CentreDepartment of Haematological MedicineKing’s College NHS Foundation TrustLondonUK
| | - Roopen Arya
- King’s Thrombosis CentreDepartment of Haematological MedicineKing’s College NHS Foundation TrustLondonUK
| | - Martin B. Whyte
- Faculty of Health & Medical SciencesUniversity of SurreyGuildfordSurreyUK
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Sobczak AIS, Katundu KGH, Phoenix FA, Khazaipoul S, Yu R, Lampiao F, Stefanowicz F, Blindauer CA, Pitt SJ, Smith TK, Ajjan RA, Stewart AJ. Albumin-mediated alteration of plasma zinc speciation by fatty acids modulates blood clotting in type-2 diabetes. Chem Sci 2021; 12:4079-4093. [PMID: 34163679 PMCID: PMC8179462 DOI: 10.1039/d0sc06605b] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 01/29/2021] [Indexed: 12/15/2022] Open
Abstract
Zn2+ is an essential regulator of coagulation and is released from activated platelets. In plasma, the free Zn2+ concentration is fine-tuned through buffering by human serum albumin (HSA). Importantly, the ability of HSA to bind/buffer Zn2+ is compromised by co-transported non-esterified fatty acids (NEFAs). Given the role of Zn2+ in blood clot formation, we hypothesise that Zn2+ displacement from HSA by NEFAs in certain conditions (such as type 2 diabetes mellitus, T2DM) impacts on the cellular and protein arms of coagulation. To test this hypothesis, we assessed the extent to which increasing concentrations of a range of medium- and long-chain NEFAs reduced Zn2+-binding ability of HSA. Amongst the NEFAs tested, palmitate (16 : 0) and stearate (18 : 0) were the most effective at suppressing zinc-binding, whilst the mono-unsaturated palmitoleate (16 : 1c9) was markedly less effective. Assessment of platelet aggregation and fibrin clotting parameters in purified systems and in pooled plasma suggested that the HSA-mediated impact of the model NEFA myristate on zinc speciation intensified the effects of Zn2+ alone. The effects of elevated Zn2+ alone on fibrin clot density and fibre thickness in a purified protein system were mirrored in samples from T2DM patients, who have derranged NEFA metabolism. Crucially, T2DM individuals had increased total plasma NEFAs compared to controls, with the concentrations of key saturated (myristate, palmitate, stearate) and mono-unsaturated (oleate, cis-vaccenate) NEFAs positively correlating with clot density. Collectively, these data strongly support the concept that elevated NEFA levels contribute to altered coagulation in T2DM through dysregulation of plasma zinc speciation.
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Affiliation(s)
- Amélie I S Sobczak
- School of Medicine, University of St Andrews Fife KY16 9TF St Andrews UK +44 (0)1334 463482 +44 (0)1334 463546
| | - Kondwani G H Katundu
- School of Medicine, University of St Andrews Fife KY16 9TF St Andrews UK +44 (0)1334 463482 +44 (0)1334 463546
- College of Medicine, University of Malawi Blantyre Malawi
| | - Fladia A Phoenix
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds Leeds UK
| | - Siavash Khazaipoul
- School of Medicine, University of St Andrews Fife KY16 9TF St Andrews UK +44 (0)1334 463482 +44 (0)1334 463546
| | - Ruitao Yu
- School of Medicine, University of St Andrews Fife KY16 9TF St Andrews UK +44 (0)1334 463482 +44 (0)1334 463546
- Key Laboratory of Tibetan Medicine Research, Northwest Plateau Institute of Biology, Chinese Academy of Sciences 23 Xinning Road Xining Qinghai 810001 China
| | - Fanuel Lampiao
- College of Medicine, University of Malawi Blantyre Malawi
| | - Fiona Stefanowicz
- Scottish Trace Element and Micronutrient Diagnostic and Research Laboratory, Department of Biochemistry NHS Greater Glasgow and Clyde Glasgow UK
| | | | - Samantha J Pitt
- School of Medicine, University of St Andrews Fife KY16 9TF St Andrews UK +44 (0)1334 463482 +44 (0)1334 463546
| | - Terry K Smith
- School of Biology, Biomedical Sciences Research Complex, University of St Andrews St Andrews UK
| | - Ramzi A Ajjan
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds Leeds UK
| | - Alan J Stewart
- School of Medicine, University of St Andrews Fife KY16 9TF St Andrews UK +44 (0)1334 463482 +44 (0)1334 463546
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Ebrahim H, Asrie F, Getaneh Z. Basic Coagulation Profiles and Platelet Parameters Among Adult Type 1 and Type 2 Diabetes Patients at Dessie Referral Hospital, Northeast Ethiopia: Comparative Cross-Sectional Study. J Blood Med 2021; 12:33-42. [PMID: 33536804 PMCID: PMC7850412 DOI: 10.2147/jbm.s287136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 01/11/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Diabetes is a heterogeneous group of metabolic disorders characterized by hyperglycemia. The disease is highly associated with micro-vascular and macro-vascular complications. Thus, the main aim of this study was to compare basic coagulation profiles and platelet parameters among type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and healthy controls. METHODS A comparative cross-sectional study was conducted at Dessie Referral Hospital from February to April 2019. A total of 180 study participants consisting of (60 T1DM, 60 T2DM, and 60 healthy controls) were enrolled using a systematic random sampling technique. Basic coagulation profiles and platelet parameters were determined using the HUMACLOT JUNIOR coagulometer and DIRUI BF 6500 automated hematology analyzer respectively. Non-parametric Kruskal-Wallis test supplemented with Dunn-Bonferroni correction and Spearman rank-order correlation test were used to compare basic coagulation profiles and platelet parameters among the groups. The test result was expressed in median and interquartile range and presented in texts and tables. P-value < 0.05 was considered to be statistically significant. RESULTS Prothrombin time (PT) and international normalization ratio (INR) were significantly reduced in T2DM as compared to T1DM and healthy controls (p <0.05). Platelet distribution width (PDW) and mean platelet volume (MPV) were significantly increased in both T1DM and T2DM as compared to healthy controls (p <0.05). Moreover, PT and INR were negatively correlated with fasting blood glucose (FBG) among T1DM and PT, INR and activated partial thromboplastin time (APTT) were negatively correlated with FBG among T2DM. CONCLUSION Basic coagulation profiles and platelet parameters were significantly different between diabetes and controls where PT and INR in T2DM were significantly reduced as compared to T1DM and controls. However, PDW and MPV were significantly elevated in both T1DM and T2DM as compared to controls. Moreover, FBG was significantly negatively correlated with PT and INR among T1DM and FBG was significantly negatively correlated with PT, INR, and APTT among T2DM. Therefore, T2DM may be related to increased risk of thrombosis indicated by reduced PT and INR and high PDW and MPV than T1DM and controls. Basic coagulation profiles and platelet parameters should be regularly tested for early diagnosis and proper management of diabetes-related thrombosis.
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Affiliation(s)
- Hussen Ebrahim
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Fikir Asrie
- Department of Hematology & Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Zegeye Getaneh
- Department of Hematology & Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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Vallianou NG, Evangelopoulos A, Kounatidis D, Stratigou T, Christodoulatos GS, Karampela I, Dalamaga M. Diabetes Mellitus and SARS-CoV-2 Infection: Pathophysiologic Mechanisms and Implications in Management. Curr Diabetes Rev 2021; 17:e123120189797. [PMID: 33388022 DOI: 10.2174/1573399817666210101110253] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 10/19/2020] [Accepted: 10/24/2020] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Currently, diabetes mellitus (DM), as well as coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are major public health issues worldwide. BACKGROUND It has been suggested that patients with DM are more vulnerable to SARS-CoV-2 infection and suffer from more severe forms of the disease. METHODS A literature search was performed using PubMed, Scopus, and Google search engines. RESULTS Angiotensin-converting enzyme-2 (ACE2) is the major receptor of SARS-CoV-2 in the human host. The differential expression of ACE2 in the lungs of patients with DM makes them more susceptible to COVID-19. Additionally, acute or chronic hyperglycemia renders individuals in an immune-suppressive state, with impaired innate and adaptive immunity function, also contributing to the severity of COVID-19 infection among patients with DM. Other factors contributing to a more severe course of COVID-19 include the coexistence of obesity in T2DM, the endothelial inflammation induced by the SARS-CoV-2 infection, which aggravates the endothelial dysfunction observed in both T1DM and T2DM, and the hypercoagulability presented in COVID-19 infection that increases the thrombotic tendency in DM. CONCLUSION This review summarizes the pathophysiologic mechanisms underlying the coexistence of both pandemics as well as the current recommendations and future perspectives regarding the optimal treatment of inpatients and outpatients with DM in the era of SARS-CoV-2 infection. Notably, the currently recommended drugs for the treatment of severe COVID-19, dexamethasone and remdesivir, may cause hyperglycemia, an adverse effect that physicians should bear in mind when caring for patients with DM and COVID-19.
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Affiliation(s)
- Natalia G Vallianou
- Department of Endocrinology, 'Evangelismos' General Hospital of Athens, 45-47 Ypsilantou street, 10676 Athens, Greece
| | | | - Dimitris Kounatidis
- Department of Endocrinology, 'Evangelismos' General Hospital of Athens, 45-47 Ypsilantou street, 10676 Athens, Greece
| | - Theodora Stratigou
- Department of Endocrinology, 'Evangelismos' General Hospital of Athens, 45-47 Ypsilantou street, 10676 Athens, Greece
| | - Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 MikrasAsias street, 11527 Athens, Greece; 4Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini Street, Haidari, 12462 Athens, Greece
| | - Irene Karampela
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 MikrasAsias street, 11527 Athens, Greece; 4Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini Street, Haidari, 12462 Athens, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 MikrasAsias street, 11527 Athens, Greece; 4Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini Street, Haidari, 12462 Athens, Greece
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50
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Moin ASM, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Type 2 Diabetes Coagulopathy Proteins May Conflict With Biomarkers Reflective of COVID-19 Severity. Front Endocrinol (Lausanne) 2021; 12:658304. [PMID: 34248840 PMCID: PMC8267927 DOI: 10.3389/fendo.2021.658304] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 06/09/2021] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE Detailed proteomic analysis in a cohort of patients with differing severity of COVID-19 disease identified biomarkers within the complement and coagulation cascades as biomarkers for disease severity has been reported; however, it is unclear if these proteins differ sufficiently from other conditions to be considered as biomarkers. METHODS A prospective, parallel study in T2D (n = 23) and controls (n = 23). A hyperinsulinemic clamp was performed and normoglycemia induced in T2D [4.5 ± 0.07 mmol/L (81 ± 1.2 mg/dl)] for 1-h, following which blood glucose was decreased to ≤2.0 mmol/L (36 mg/dl). Proteomic analysis for the complement and coagulation cascades were measured using Slow Off-rate Modified Aptamer (SOMA)-scan. RESULTS Thirty-four proteins were measured. At baseline, 4 of 18 were found to differ in T2D versus controls for platelet degranulation [Neutrophil-activating peptide-2 (p = 0.014), Thrombospondin-1 (p = 0.012), Platelet factor-4 (p = 0.007), and Kininogen-1 (p = 0.05)], whilst 3 of 16 proteins differed for complement and coagulation cascades [Coagulation factor IX (p < 0.05), Kininogen-1 (p = 0.05), and Heparin cofactor-2 (p = 0.007)]; STRING analysis demonstrated the close relationship of these proteins to one another. Induced euglycemia in T2D showed no protein changes versus baseline. At hypoglycemia, however, four proteins changed in controls from baseline [Thrombospondin-1 (p < 0.014), platelet factor-4 (p < 0.01), Platelet basic protein (p < 0.008), and Vitamin K-dependent protein-C (p < 0.00003)], and one protein changed in T2D [Vitamin K-dependent protein-C, (p < 0.0002)]. CONCLUSION Seven of 34 proteins suggested to be biomarkers of COVID-19 severity within the platelet degranulation and complement and coagulation cascades differed in T2D versus controls, with further changes occurring at hypoglycemia, suggesting that validation of these biomarkers is critical. It is unclear if these protein changes in T2D may predict worse COVID-19 disease for these patients. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov/, identifier NCT03102801.
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Affiliation(s)
- Abu Saleh Md Moin
- Diabetes Research Center (DRC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar
| | - Ahmed Al-Qaissi
- Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull, United Kingdom
- Department of Endocrinology, Leeds Medical School, Leeds, United Kingdom
| | - Thozhukat Sathyapalan
- Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull, United Kingdom
| | - Stephen L. Atkin
- Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain
| | - Alexandra E. Butler
- Diabetes Research Center (DRC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar
- *Correspondence: Alexandra E. Butler, ;
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