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Hu H, Zhu Y, Hu R, Zhao L, Zeng X, Wu X, Qiu R, Nie Y, Sharma L, Chang D. Prophylactic anticoagulant therapy is associated with improved survival in ICU patients with non-COVID-19 pneumonia: a retrospective cohort study. Front Pharmacol 2025; 16:1597885. [PMID: 40406481 PMCID: PMC12095157 DOI: 10.3389/fphar.2025.1597885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2025] [Accepted: 04/23/2025] [Indexed: 05/26/2025] Open
Abstract
Background Coagulation disorders are common complications in patients with pulmonary infections. Studies have suggested beneficial effects of anticoagulant therapies in patients with COVID-19. However, the usefulness of prophylactic anticoagulant therapies in patients with non-COVID-19 pulmonary infections is still a matter of debate. This study aimed to assessed the impact of prophylactic anticoagulant therapy in ICU patients with non-COVID-19 pneumonia. Methods Patients were identified from the Medical Information Mart for Intensive Care-IV database. Propensity score matching (PSM) was utilized to minimize differences. Kaplan-Meier survival analysis was performed to assess mortality. Univariate and multivariate Cox regression models were used to identify prognostic factors for short-term mortality (7-day). The E-value was calculated to unmeasured confounding. To further explore the optimal anticoagulant administration, subgroup analyses were performed. We also explored the optimal administration strategies including the timing and duration of anticoagulant therapy. Results A total of 1,000 ICU patients were included, with 500 receiving prophylactic anticoagulation therapy and 500 not. Both 7-day mortality (7.6% vs. 19.6%; p < 0.001) and 30-day mortality (19.6% vs. 31.2%; p < 0.001) in the anticoagulant group were lower than non-users. Kaplan-Meier survival analysis also showed a significantly lower prevalence of short-term mortality in patients who used anticoagulants. Both univariate (HR, 0.36; 95% CI, 0.25-0.53; p < 0.001) and multivariate (HR, 0.30; 95% CI, 0.21-0.44; p < 0.001) Cox regression analyses consistently demonstrated a significant reduction in short-term mortality associated with anticoagulation therapy. Subgroup analysis revealed that anticoagulant therapy was associated with reduced short-term mortality across most subgroups. Further analysis showed that late (≥6 h) and non-short-term (≥7 days) anticoagulation therapy were more effective. Conclusion Our results support the potential value of prophylactic anticoagulation therapy as a strategy to improve survival in ICU patients with non-COVID-19 pneumonia.
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Affiliation(s)
- Haiming Hu
- Department of Pulmonary and Critical Care Medicine at The Seventh Medical Center, College of Pulmonary and Critical Care Medicine of The Eighth Medical Center, Chinese PLA General Hospital, Beijing, China
- Graduate School of Chinese PLA General Hospital, Beijing, China
| | - Yixing Zhu
- Department of Pulmonary and Critical Care Medicine at The Seventh Medical Center, College of Pulmonary and Critical Care Medicine of The Eighth Medical Center, Chinese PLA General Hospital, Beijing, China
- Graduate School of Chinese PLA General Hospital, Beijing, China
| | - Ruikang Hu
- Graduate School of Chinese PLA General Hospital, Beijing, China
| | - Lijuan Zhao
- Graduate School of Chinese PLA General Hospital, Beijing, China
- Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Xiangwen Zeng
- Graduate School of Chinese PLA General Hospital, Beijing, China
| | - Xue Wu
- Department of Pulmonary and Critical Care Medicine at The Seventh Medical Center, College of Pulmonary and Critical Care Medicine of The Eighth Medical Center, Chinese PLA General Hospital, Beijing, China
- Graduate School of Chinese PLA General Hospital, Beijing, China
| | - Rui Qiu
- Department of Pulmonary and Critical Care Medicine at The Seventh Medical Center, College of Pulmonary and Critical Care Medicine of The Eighth Medical Center, Chinese PLA General Hospital, Beijing, China
- Graduate School of Chinese PLA General Hospital, Beijing, China
| | - Yihao Nie
- Sanquan College, Xinxiang Medical College, Xinxiang, Henan, China
| | - Lokesh Sharma
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - De Chang
- Department of Pulmonary and Critical Care Medicine at The Seventh Medical Center, College of Pulmonary and Critical Care Medicine of The Eighth Medical Center, Chinese PLA General Hospital, Beijing, China
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Aisanjiang M, Dai W, Wu L, Yuan Y, Liu S, Liao G, Li L, Tong X, Zhang H, Chen Y, Liu J, Cheng J, Wang C, Lu Y. Ameliorating lung fibrosis and pulmonary function in diabetic mice: Therapeutic potential of mesenchymal stem cell. Biochem Biophys Res Commun 2024; 737:150495. [PMID: 39126861 DOI: 10.1016/j.bbrc.2024.150495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 07/27/2024] [Accepted: 08/01/2024] [Indexed: 08/12/2024]
Abstract
This study aimed to investigate the potential of mesenchymal stem cells (MSCs) in alleviating diabetic lung injury by decreasing inflammation, fibrosis and recovering tissue macrophage homeostasis. To induce pulmonary injuries in an in vivo murine model, we utilized a streptozotocin (STZ), and high-fat diet (HFD) induced diabetic C57 mouse model. Subsequently, human umbilical cord-derived MSCs (hUC-MSCs) were administered through the tail vein on a weekly basis for a duration of 4 weeks. In addition, in vitro experiments involved co-culturing of isolated primary abdominal macrophages from diabetic mice and high glucose-stimulated MLE-12 cells with hUC-MSCs. The objective was to evaluate if hUC-MSCs co-culturing could effectively mitigate cell inflammation and fibrosis. Following hUC-MSCs injection, diabetic mice displayed enhanced pulmonary functional parameters, reduced pulmonary fibrosis, and diminished inflammation. Notably, the dynamic equilibrium of lung macrophages shifted from the M1 phenotype to the M2 phenotype, accompanied by a notable reduction in various indicators associated with inflammation and fibrosis. Results from cell co-culturing experiments further supported this trend, demonstrating a reduction in inflammatory and fibrotic indicators. In conclusion, our findings suggest that hUC-MSCs treatment holds promise in mitigating diabetic pulmonary injury by significantly reducing inflammation, fibrosis and maintain tissue macrophage homeostasis within the lungs. This study sheds light on the therapeutic potential of hUC-MSCs in managing diabetic complications affecting the pulmonary system.
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Affiliation(s)
- Maikeliya Aisanjiang
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Wenshu Dai
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Luna Wu
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Yujia Yuan
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Shuyun Liu
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Guangneng Liao
- Animal experimental center of West China hospital, Sichuan University, Chengdu, China
| | - Lan Li
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Xiang Tong
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Heteng Zhang
- Sichuan Neo-Life Stem Cell Biotech Inc., Chengdu, China
| | - Younan Chen
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Jingping Liu
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Jingqiu Cheng
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Chengshi Wang
- Department of Endocrinology and Metabolism, Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, China.
| | - Yanrong Lu
- Department of Respiratory and Critical Care Medicine, Key Laboratory of Transplant Engineering and Immunology, NHFPC, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
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Padte S, Mehta P, Bansal V, singh N, Sunasra R, Goyal V, Chaudhary RB, Junnarkar Y, Shah V, Arshad Z, Nawaz FA, Surani S, Kashyap R. Impact of diabetes mellitus on mortality in pulmonary hypertension: A systematic review and meta-analysis. World J Crit Care Med 2024; 13:99564. [PMID: 39655305 PMCID: PMC11577532 DOI: 10.5492/wjccm.v13.i4.99564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 09/05/2024] [Accepted: 09/23/2024] [Indexed: 10/31/2024] Open
Abstract
BACKGROUND Pulmonary hypertension (PH) is a progressive disease characterized by endothelial dysfunction and vascular remodeling and is a leading cause of mortality worldwide. Although it is independently associated with multiple comorbidities, the impact of diabetes mellitus (DM) on mortality in patients with PH remains uncertain. To address this issue, we conducted a systematic review and meta-analysis to investigate the effect of DM on survival in patients with pulmonary hypertension. AIM To investigate the impact of diabetes mellitus on mortality in pulmonary hypertension patients. METHODS We conducted a comprehensive search of four major electronic bibliographic databases like PubMed, Google Scholar, Scopus, and Embase, and identified 106 relevant studies, out of 1561 articles, published since the year 2000 for full-text review. Fourteen retrospective and prospective cohort studies that compared survival between patients with DM and those without DM in the context of PH were deemed eligible for inclusion in our meta-analysis. The study was registered on PROSPERO with the identifier CRD42023390232. RESULTS A total of 116455 patients with PH were included in the meta-analysis, of whom 41228 suffered from DM and 75227 did not. The results of our meta-analysis indicate an elevated mortality rate among PH patients with diabetes mellitus in comparison to those without DM [odds ratio (OR) = 1.40, 95%CI: 1.15-1.70, P = 0.0006]. The meta-regression analysis unveiled a statistically significant negative association between mean age and effect size (coefficient = -0.036, P value = 0.018). Conversely, a statistically significant positive association was detected between female proportion and effect size (coefficient = 0.000, P value < 0.001). CONCLUSION Our meta-analysis, which included approximately 116500 PH patients, revealed that the presence of diabetes mellitus was associated with increased odds of mortality when compared to non-diabetic patients. The meta-regression analysis indicates that studies with older participants and lower proportions of females tend to exhibit smaller effect sizes. Clinically, these findings underscore the importance of incorporating diabetes status into the risk stratification of patients with PH with more aggressive monitoring and early intervention to improve prognosis potentially.
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Affiliation(s)
- Smitesh Padte
- Department of Research, Global Remote Research Scholar Program, Princeton Junction, Princeton, NJ 08550, United States
- Department of Internal Medicine, WellSpan York Hospital, York, PA 17403, United States
| | - Priyal Mehta
- Department of Research, Global Remote Research Scholar Program, Princeton Junction, Princeton, NJ 08550, United States
- Department of Internal Medicine, St. Vincent Hospital, Worchester, MA 01608, United States
| | - Vikas Bansal
- Department of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55902, United States
| | - Niti singh
- Department of Anesthesiology and Critical Care, Seth G. S. Medical College and K.E.M. Hospital, Mumbai 400012, Mahārāshtra, India
| | - Rayyan Sunasra
- Department of Medicine, Hinduhridaysamrat Balasaheb Thackeray Medical College and Dr. R. N Cooper Hospital, Mumbai 400056, India
| | - Vidhi Goyal
- Department of Medicine, HBT Medical College and Dr. RN Cooper Hospital, Mumbai 400056, Mahārāshtra, India
| | - Raunaq B Chaudhary
- Department of Medicine, HBT Medical College and Dr. RN Cooper Hospital, Mumbai 400056, Mahārāshtra, India
| | - Yash Junnarkar
- Department of Medicine, HBT Medical College and Dr. RN Cooper Hospital, Mumbai 400056, Mahārāshtra, India
| | - Vidhi Shah
- Department of Medicine, HBT Medical College and Dr. RN Cooper Hospital, Mumbai 400056, Mahārāshtra, India
| | - Zara Arshad
- Department of Research, Global Remote Research Scholar Program, Princeton Junction, Princeton, NJ 08550, United States
| | - Faisal A Nawaz
- Department of Research, Global Remote Research Scholar Program, Princeton Junction, Princeton, NJ 08550, United States
- Department of Psychiatry, Al Amal Psychiatry Hospital, Dubai 50262, Dubayy, United Arab Emirates
| | - Salim Surani
- Department of Research, Global Remote Research Scholar Program, Princeton Junction, Princeton, NJ 08550, United States
- Department of Medicine & Pharmacology, Texas A&M University, College Station, TX 77843, United States
| | - Rahul Kashyap
- Department of Research, Global Remote Research Scholar Program, Princeton Junction, Princeton, NJ 08550, United States
- Department of Research, Wellspan Health, York, PA 17403, United States
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Sheraz S, Malik AN, Ferraro FV, Siddiqi FA. Multifactorial inspiratory muscle training and its impact on respiratory and functional parameters of patients with diabetic polyneuropathy-A Randomized Controlled Trial. PHYSIOTHERAPY RESEARCH INTERNATIONAL 2024; 29:e2127. [PMID: 39234855 DOI: 10.1002/pri.2127] [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: 10/16/2023] [Revised: 08/01/2024] [Accepted: 08/21/2024] [Indexed: 09/06/2024]
Abstract
BACKGROUND AND PURPOSE Diabetic polyneuropathy is a long-standing microvascular complication of diabetes that affects the postural control and functional mobility of patients. There are other microvascular complications, including pulmonary complications that reduce lung function. Multifactorial Inspiratory Muscle Training (IMT) can act as a home-based technique targeted to affect both these complications. This study aims to determine the effects of IMT on respiratory and functional parameters in diabetic polyneuropathy patients. METHODS This is a Pre-Test Post-Test Randomized Controlled Trial (NCT#04947163) with 62 diabetic polyneuropathy patients. Each was randomly assigned to the IMT or sham-IMT group. Both the groups performed OTAGO exercises , with the sham-IMT group performing IMT at 15% of baseline maximal inspiratory pressure (MIP), whereas IMT were trained at 50% of baseline MIP as an initial intensity, which was increased as per the tolerance of patients. Both groups performed training for 12 weeks. The study investigated diaphragmatic strength, pulmonary function, functional capacity through 6MWT, 30s sit to stand test and anterior trunk muscle endurance tested through sit up test as outcome variables. Data was analysed on SPSS v26 at the significance level of 0.0.5. RESULTS The IMT group significantly improved diaphragmatic strength, pulmonary function, 6MWT and anterior trunk muscle endurance when compared to the sham-IMT group. CONCLUSION The study concluded that home-based IMT can improve pulmonary parameters including diaphragmatic strength and lung function as well as functional parameters including functional capacity in patients with diabetic polyneuropathy. The study was registered at ClinicalTrials.gov, NCT#04947163.
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Affiliation(s)
- Suman Sheraz
- Faculty of Rehabilitation & Allied Health Sciences, Riphah International University, Islamabad, Pakistan
| | - Arshad Nawaz Malik
- Faculty of Rehabilitation & Allied Health Sciences, Riphah International University, Islamabad, Pakistan
| | | | - Furqan Ahmed Siddiqi
- Foundation University College of Physical Therapy, Foundation University Islamabad, Islamabad, Pakistan
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Mo C, Yan M, Tang XX, Shichino S, Bagnato G. Editorial: Cellular and molecular mechanisms of lung regeneration, repair, and fibrosis. Front Cell Dev Biol 2024; 11:1346875. [PMID: 38259517 PMCID: PMC10801291 DOI: 10.3389/fcell.2023.1346875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 12/26/2023] [Indexed: 01/24/2024] Open
Affiliation(s)
- Chunheng Mo
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Mengli Yan
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China
- Institute of Hematology, Henan Key Laboratory of Stem Cell Differentiation and Modification, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan, China
| | - Xiao Xiao Tang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Guangzhou Laboratory, Bio-Island, Guangzhou, China
| | - Shigeyuki Shichino
- Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, Chiba, Japan
| | - Gianluca Bagnato
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Pantea Stoian A, Bica IC, Salmen T, Al Mahmeed W, Al-Rasadi K, Al-Alawi K, Banach M, Banerjee Y, Ceriello A, Cesur M, Cosentino F, Firenze A, Galia M, Goh SY, Janez A, Kalra S, Kapoor N, Kempler P, Lessan N, Lotufo P, Mikhailidis DP, Nibali L, Papanas N, Powell-Wiley T, Rizvi AA, Sahebkar A, Santos RD, Toth PP, Viswanathan V, Rizzo M. New-Onset Diabetes Mellitus in COVID-19: A Scoping Review. Diabetes Ther 2024; 15:33-60. [PMID: 37751143 PMCID: PMC10786767 DOI: 10.1007/s13300-023-01465-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 08/15/2023] [Indexed: 09/27/2023] Open
Abstract
INTRODUCTION The coronavirus disease 2019 (COVID-19) pandemic became superimposed on the pre-existing obesity and diabetes mellitus (DM) pandemics. Since COVID-19 infection alters the metabolic equilibrium, it may induce pathophysiologic mechanisms that potentiate new-onset DM, and we evaluated this issue. METHOD A systematic review of the literature published from the 1 January 2020 until the 20 July 2023 was performed (PROSPERO registration number CRD42022341638). We included only full-text articles of both human clinical and randomized controlled trials published in English and enrolling adults (age > 18 years old) with ongoing or preceding COVID-19 in whom hyperglycemia was detected. The search was based on the following criteria: "(new-onset diabetes mellitus OR new-onset DM) AND (COVID-19) AND adults". RESULTS Articles on MEDLINE (n = 70) and the Web of Science database (n = 16) were included and analyzed by two researchers who selected 20 relevant articles. We found evidence of a bidirectional relationship between COVID-19 and DM. CONCLUSIONS This link operates as a pathophysiological mechanism supported by epidemiological data and also by the clinical and biological findings obtained from the affected individuals. The COVID-19 pandemic raised the incidence of DM through different pathophysiological and psychosocial factors.
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Affiliation(s)
- Anca Pantea Stoian
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Doctoral School, "Carol Davila" University of Medicine and Pharmacy, 020021, Bucharest, Romania
| | - Ioana-Cristina Bica
- Doctoral School, "Carol Davila" University of Medicine and Pharmacy, 020021, Bucharest, Romania.
| | - Teodor Salmen
- Doctoral School, "Carol Davila" University of Medicine and Pharmacy, 020021, Bucharest, Romania
| | - Wael Al Mahmeed
- Heart and Vascular Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates
| | | | - Kamila Al-Alawi
- Department of Training and Studies, Royal Hospital, Ministry of Health, Muscat, Oman
| | - Maciej Banach
- Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Lodz, Poland
- Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
- Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland
| | - Yajnavalka Banerjee
- Department of Biochemistry, Mohamed Bin Rashid University, Dubai, United Arab Emirates
| | | | - Mustafa Cesur
- Clinic of Endocrinology, Ankara Güven Hospital, Ankara, Turkey
| | - Francesco Cosentino
- Unit of Cardiology, Karolinska Institute and Karolinska University Hospital, University of Stockholm, Stockholm, Sweden
| | - Alberto Firenze
- Unit of Research and International Cooperation, University Hospital of Palermo, Palermo, Italy
| | - Massimo Galia
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (Bind), University of Palermo, Palermo, Italy
| | - Su-Yen Goh
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Andrej Janez
- Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia
| | - Sanjay Kalra
- Department of Endocrinology, Bharti Hospital and Bride, Karnal, India
| | - Nitin Kapoor
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India
- Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - Peter Kempler
- Department of Medicine and Oncology, Semmelweis University, Budapest, Hungary
| | - Nader Lessan
- The Research Institute, Imperial College London Diabetes Centre, Abu Dhabi, United Arab Emirates
| | - Paulo Lotufo
- Center for Clinical and Epidemiological Research, University Hospital, University of São Paulo, Sao Paulo, Brazil
| | - Dimitri P Mikhailidis
- Department of Biochemistry, Mohamed Bin Rashid University, Dubai, United Arab Emirates
- Department of Clinical Biochemistry, Royal Free Hospital Campus, University College London Medical School, University College London (UCL), London, UK
| | - Luigi Nibali
- Dental Institute, Periodontology Unit, Centre for Host-Microbiome Interactions, King's College London, London, UK
| | - Nikolaos Papanas
- Diabetes Center, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Tiffany Powell-Wiley
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, Cardiovascular Branch, Division of Intramural Research, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Ali A Rizvi
- Department of Medicine, University of Central Florida College of Medicine, Orlando, FL, USA
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sci-Ences, Mashhad, Iran
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Raul D Santos
- Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil
- Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Peter P Toth
- Hospital Israelita Albert Einstein, Sao Paulo, Brazil
- Cicarrone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medi-Cine, Baltimore, MD, USA
| | | | - Manfredi Rizzo
- Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Biochemistry, Mohamed Bin Rashid University, Dubai, United Arab Emirates
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMise), School of Medicine, University of Palermo, Palermo, Italy
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Mauricio D, Gratacòs M, Franch-Nadal J. Diabetic microvascular disease in non-classical beds: the hidden impact beyond the retina, the kidney, and the peripheral nerves. Cardiovasc Diabetol 2023; 22:314. [PMID: 37968679 PMCID: PMC10652502 DOI: 10.1186/s12933-023-02056-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 11/07/2023] [Indexed: 11/17/2023] Open
Abstract
Diabetes microangiopathy, a hallmark complication of diabetes, is characterised by structural and functional abnormalities within the intricate network of microvessels beyond well-known and documented target organs, i.e., the retina, kidney, and peripheral nerves. Indeed, an intact microvascular bed is crucial for preserving each organ's specific functions and achieving physiological balance to meet their respective metabolic demands. Therefore, diabetes-related microvascular dysfunction leads to widespread multiorgan consequences in still-overlooked non-traditional target organs such as the brain, the lung, the bone tissue, the skin, the arterial wall, the heart, or the musculoskeletal system. All these organs are vulnerable to the physiopathological mechanisms that cause microvascular damage in diabetes (i.e., hyperglycaemia-induced oxidative stress, inflammation, and endothelial dysfunction) and collectively contribute to abnormalities in the microvessels' structure and function, compromising blood flow and tissue perfusion. However, the microcirculatory networks differ between organs due to variations in haemodynamic, vascular architecture, and affected cells, resulting in a spectrum of clinical presentations. The aim of this review is to focus on the multifaceted nature of microvascular impairment in diabetes through available evidence of specific consequences in often overlooked organs. A better understanding of diabetes microangiopathy in non-target organs provides a broader perspective on the systemic nature of the disease, underscoring the importance of recognising the comprehensive range of complications beyond the classic target sites.
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Affiliation(s)
- Dídac Mauricio
- DAP-Cat group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain.
- Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, IR Sant Pau, Barcelona, Spain.
- Department of Medicine, University of Vic - Central University of Catalonia, Vic, Spain.
| | - Mònica Gratacòs
- DAP-Cat group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
| | - Josep Franch-Nadal
- DAP-Cat group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
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Joshi SR, Atabay EK, Liu J, Ding Y, Briscoe SD, Alexander MJ, Andre P, Kumar R, Li G. Sotatercept analog improves cardiopulmonary remodeling and pulmonary hypertension in experimental left heart failure. Front Cardiovasc Med 2023; 10:1064290. [PMID: 36910526 PMCID: PMC9996114 DOI: 10.3389/fcvm.2023.1064290] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 01/19/2023] [Indexed: 02/25/2023] Open
Abstract
Pulmonary hypertension due to left heart disease (PH-LHD) is the most frequent manifestation of PH but lacks any approved treatment. Activin receptor type IIA-Fc fusion protein (ActRIIA-Fc) was found previously to be efficacious in experimental and human pulmonary arterial hypertension (PAH). Here we tested the hypothesis that ActRIIA-Fc improves pulmonary vascular remodeling and alleviates PH in models of PH-LHD, specifically in subtypes of heart failure with reduced ejection fraction (PH-HFrEF) and preserved ejection fraction (PH-HFpEF). Treatment with murine ActRIIA-Fc reduced cardiac remodeling and improved cardiac function in two mouse models of left heart disease without PH, confirming that this inhibitor of activin-class ligand signaling can exert cardioprotective effects in heart failure. In a mouse model of PH-HFrEF with prolonged pressure overload caused by transverse aortic constriction, ActRIIA-Fc treatment significantly reduced pulmonary vascular remodeling, pulmonary fibrosis, and pulmonary hypertension while exerting beneficial structural, functional, and histological effects on both the left and right heart. Additionally, in an obese ZSF1-SU5416 rat model of PH-HFpEF with metabolic dysregulation, therapeutic treatment with ActRIIA-Fc normalized SMAD3 overactivation in pulmonary vascular and perivascular cells, reversed pathologic pulmonary vascular and cardiac remodeling, improved pulmonary and cardiac fibrosis, alleviated PH, and produced marked functional improvements in both cardiac ventricles. Studies in vitro revealed that treatment with ActRIIA-Fc prevents an abnormal, glucose-induced, activin-mediated, migratory phenotype in human pulmonary artery smooth muscle cells, providing a mechanism by which ActRIIA-Fc could exert therapeutic effects in experimental PH-HFpEF with metabolic dysregulation. Our results demonstrate that ActRIIA-Fc broadly corrects cardiopulmonary structure and function in experimental PH-LHD, including models of PH-HFrEF and PH-HFpEF, leading to alleviation of PH under diverse pathophysiological conditions. These findings highlight the important pathogenic contributions of activin-class ligands in multiple forms of experimental PH and support ongoing clinical evaluation of human ActRIIA-Fc (sotatercept) in patients with PH-HFpEF.
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Affiliation(s)
- Sachindra R Joshi
- Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, United States
| | - Elif Karaca Atabay
- Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, United States
| | - Jun Liu
- Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, United States
| | - Yan Ding
- Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, United States
| | - Steven D Briscoe
- Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, United States
| | - Mark J Alexander
- Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, United States
| | - Patrick Andre
- Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, United States
| | - Ravindra Kumar
- Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, United States
| | - Gang Li
- Discovery Group, Acceleron Pharma Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ, United States
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9
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Dehghani P, Schmidt CW, Garcia S, Okeson B, Grines CL, Singh A, Patel RA, Wiley J, Htun WW, Nayak KR, Alraies MC, Ghasemzadeh N, Davidson LJ, Acharya D, Stone J, Alyousef T, Case BC, Dai X, Hafiz AM, Madan M, Jaffer FA, Shavadia JS, Garberich R, Bagai A, Singh J, Aronow HD, Mercado N, Henry TD. North American COVID-19 Myocardial Infarction (NACMI) Risk Score for Prediction of In-Hospital Mortality. JOURNAL OF THE SOCIETY FOR CARDIOVASCULAR ANGIOGRAPHY & INTERVENTIONS 2022; 1:100404. [PMID: 35845345 PMCID: PMC9270689 DOI: 10.1016/j.jscai.2022.100404] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 06/07/2022] [Accepted: 06/14/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND In-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is higher in those with COVID-19 than in those without COVID-19. The factors that predispose to this mortality rate and their relative contribution are poorly understood. This study developed a risk score inclusive of clinical variables to predict in-hospital mortality in patients with COVID-19 and STEMI. METHODS Baseline demographic, clinical, and procedural data from patients in the North American COVID-19 Myocardial Infarction registry were extracted. Univariable logistic regression was performed using candidate predictor variables, and multivariable logistic regression was performed using backward stepwise selection to identify independent predictors of in-hospital mortality. Independent predictors were assigned a weighted integer, with the sum of the integers yielding the total risk score for each patient. RESULTS In-hospital mortality occurred in 118 of 425 (28%) patients. Eight variables present at the time of STEMI diagnosis (respiratory rate of >35 breaths/min, cardiogenic shock, oxygen saturation of <93%, age of >55 years, infiltrates on chest x-ray, kidney disease, diabetes, and dyspnea) were assigned a weighted integer. In-hospital mortality increased exponentially with increasing integer risk score (Cochran-Armitage χ2, P < .001), and the model demonstrated good discriminative power (c-statistic = 0.81) and calibration (Hosmer-Lemeshow, P = .40). The increasing risk score was strongly associated with in-hospital mortality (3.6%-60% mortality for low-risk and very high-risk score categories, respectively). CONCLUSIONS The risk of in-hospital mortality in patients with COVID-19 and STEMI can be accurately predicted and discriminated using readily available clinical information.
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Affiliation(s)
- Payam Dehghani
- Prairie Vascular Research Inc, Regina, Saskatchewan, Canada
| | | | - Santiago Garcia
- Minneapolis Heart Institute Foundation, Minneapolis, Minnesota
| | - Brynn Okeson
- Minneapolis Heart Institute Foundation, Minneapolis, Minnesota
| | | | - Avneet Singh
- Long Island Jewish Medical Center and North Shore University Hospital, New Hyde Park, New York
| | | | - Jose Wiley
- Albert Einstein College of Medicine, Montefiore Health System, New York, New York
| | | | - Keshav R. Nayak
- Department of Cardiology, Scripps Mercy Hospital, San Diego, California
| | | | | | - Laura J. Davidson
- Northwestern University, Feinberg School of Medicine, Chicago, Illinois
| | - Deepak Acharya
- University of Arizona Sarver Heart Center, Tucson, Arizona
| | - Jay Stone
- Community Medical Center (RWJ Barnabas Health), Toms River, New Jersey
| | - Tareq Alyousef
- Cook County Health and Hospitals System, Chicago, Illinois
| | - Brian C. Case
- MedStar Washington Hospital Center, Washington, District of Columbia
| | - Xuming Dai
- NewYork-Presbyterian Queens, Flushing, New York
| | - Abdul Moiz Hafiz
- Southern Illinois University School of Medicine, Springfield, Illinois
| | - Mina Madan
- Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | | | - Jay S. Shavadia
- Royal University Hospital (Saskatchewan Health), University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Ross Garberich
- Minneapolis Heart Institute Foundation, Minneapolis, Minnesota
| | - Akshay Bagai
- St. Michael’s Hospital, Toronto, Ontario, Canada
| | - Jyotpal Singh
- Prairie Vascular Research Inc, Regina, Saskatchewan, Canada
| | - Herbert D. Aronow
- Alpert Medical School of Brown University and Lifespan Cardiovascular Institute, Providence, Rhode Island
| | | | - Timothy D. Henry
- The Carl and Edyth Lindner Center for Research and Education, The Christ Hospital, Cincinnati, Ohio
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10
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Yang J, Jiang S. Development and Validation of a Model That Predicts the Risk of Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study. Int J Gen Med 2022; 15:5089-5101. [PMID: 35645579 PMCID: PMC9130557 DOI: 10.2147/ijgm.s363474] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 05/12/2022] [Indexed: 12/19/2022] Open
Abstract
Purpose To develop a nomogram model that predicts the risk of diabetic nephropathy (DN) incidence in type 2 diabetes mellitus (T2DM) patients. Methods We collect information from electronic medical record systems. The data were split into a training set (n=521) containing 73.8% of patients and a validation set (n=185) holding the remaining 26.2% of patients based on the date of data collection. Stepwise and multivariable logistic regression analyses were used to screen out DN risk factors. A predictive model including selected risk factors was developed by logistic regression analysis. The results of binary logistic regression are presented through forest plots and nomogram. Lastly, the c-index, calibration plots, and receiver operating characteristic (ROC) curves were used to assess the accuracy of the nomogram in internal and external validation. The clinical benefit of the model was evaluated by decision curve analysis. Results Predictors included serum creatinine (Scr), hypertension, glycosylated hemoglobin A1c (HbA1c), blood urea nitrogen (BUN), body mass index (BMI), triglycerides (TG), and Diabetic peripheral neuropathy (DPN). Harrell's C-indexes were 0.773 (95% CI:0.726-0.821) and 0.758 (95% CI:0.679-0.837) in the training and validation sets, respectively. Decision curve analysis (DCA) demonstrated that the novel nomogram was clinically valuable. Conclusion Our simple nomogram with seven factors may help clinicians predict the risk of DN incidence in patients with T2DM.
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Affiliation(s)
- Jing Yang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia; Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830017, People’s Republic of China
| | - Sheng Jiang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia; Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830017, People’s Republic of China
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11
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Patgiri PR, Rajendran V, Ahmed AB. Clinico-Epidemiological Profiles of COVID-19 Elderly Patients in Guwahati City, Assam, India: A Cross-Sectional Study. Cureus 2022; 14:e24043. [PMID: 35573552 PMCID: PMC9094510 DOI: 10.7759/cureus.24043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/09/2022] [Indexed: 01/08/2023] Open
Abstract
Background As of November 14, 2021, coronavirus disease 2019 (COVID-19 has affected more than 3,44,00,000 individuals in India and resulted in more than 4,60,000 deaths in India.Symptoms of COVID-19 include cough, fever, dyspnea, diarrhea, fatigue, expectoration, myalgia, hemoptysis, abdominal pain, and anorexia.Associated comorbidities such as hypertension, diabetes, cardiovascular illness, and respiratory sicknesses influence the severity and prognosis of the COVID-19. Therefore, this study was conducted to determine the factors associated with the severity and outcome of elderly Indian people diagnosed with COVID-19. Methodology This hospital-based descriptive cross-sectional study was conducted among elderly patients with confirmed COVID-19 who were admitted to Gauhati Medical College Hospital from July 21, 2020, to January 15, 2021. The demographic data, exposure history, clinical symptoms and signs, underlying comorbidity, severity of COVID-19, and outcome data of each elderly patient were obtained and analyzed using SPSS software (Version 25.0, IBM Corp., Armonk, NY). The Fisher exact test, chi-square test, and binary logistic regression analysis were used for different study variables. Result A total of 165 hospitalized COVID-19 elderly patients were included in this study, and their mean age was 68.4 years. The most common symptoms were cough (34.5%), fever (28%), breathing difficulty (22%), weakness (13.1%), and chest pain (3.6%). Those with breathing difficulty (adjusted OR [aOR]: 7.293, 95% CI: 2.229-23.860, p=0.001), loose stool (aOR: 12.142, 95% CI: 1.052-140.209, p=0.045), hypertension (aOR: 2.703, 95% CI: 1.023-7.139, p=0.045), and severity of COVID-19 (aOR: 7.691, 95% CI: 2.870-20.607, P<0.001) had increased risk of poor outcome among the COVID-19 elderly. Being hypertensive (aOR: 2.474, 95% CI: 1.060-5.774, p=0.036) had an increased risk of severity of COVID-19. Conclusion The most common symptoms of COVID‐19 elderly patients were fever, cough, and breathing difficulty. In elderly COVID-19 patients, hypertension played a crucial role in determining the severity of COVID-19, whereas breathing difficulty, loose stool, hypertension, and moderate-to-severe COVID-19 elderly patients had a poor outcome.
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12
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Estedlal A, Jeddi M, Heydari ST, Jahromi MG, Dabbaghmanesh MH. Impacts of diabetes mellitus on clinical and para-clinical parameters among COVID-19 patients. J Diabetes Metab Disord 2021; 20:1211-1219. [PMID: 34277497 PMCID: PMC8278179 DOI: 10.1007/s40200-021-00844-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 06/21/2021] [Indexed: 01/08/2023]
Abstract
PURPOSE Diabetes has several adverse effects on patients with coronavirus disease 2019 (COVID-19); however, the determinants of this effect are still poorly understood. It is tried in current study to evaluate impacts of type 2 diabetes, with and without other comorbidities, on the clinical, para-clinical, and outcome parameters among COVID-19 patients. METHODS A case series was applied, which involved 406 COVID-19 patients admitted in the city of Shiraz, south-central Iran, from February 20 to April 29, 2020. Demographic data, medical history, laboratory finding, chest computed tomography (CT) scan reports, and clinical outcomes of patients with and without type 2 diabetes were compared. RESULTS Results of the above-mentioned comparison showed that comorbidities such as HTN (35.5% vs. 13.7%, p < 0.001) and CVDs (26.2% vs. 13.4%, P = 0.002) were significantly more prevalent among the diabetic patients. Also, there was not any considerable difference between the chest CT severity parameters of both groups. After excluding all of the comorbidities except diabetes, it was found that the diabetic COVID-19 patients without other comorbidities had lower oxygen saturation level (P < 0.001), higher AST level (P = 0.037), higher BUN (P = 0.005), higher WBC counts (P = 0.025), lower lymphocyte counts (P = 0.029), and longer ICU admission duration (0.72 ± 2.83 vs. 1.71 ± 4.68, P = 0.046). CONCLUSION The diabetic COVID patients are at higher risks of hypoxemia, longer ICU stays, and more renal and hepatic dysfunction. These achievements could be useful in order to prevent the deterioration of clinical conditions among diabetic COVID-19 patients; also, they have to be considered in the management strategies.
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Affiliation(s)
- AliReza Estedlal
- Health Policy Research Center, Institute of Heath, Shiraz University of Medical Sciences, Shiraz, Fars Iran
| | - Marjan Jeddi
- Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Taghi Heydari
- Health Policy Research Center, Institute of Heath, Shiraz University of Medical Sciences, Shiraz, Fars Iran
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Sabri S, Bourron O, Phan F, Nguyen LS. Interactions between diabetes and COVID-19: A narrative review. World J Diabetes 2021; 12:1674-1692. [PMID: 34754370 PMCID: PMC8554367 DOI: 10.4239/wjd.v12.i10.1674] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 06/29/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes, whether due to pancreatic beta cells insufficiency or peripheral resistance to insulin, has been suggested as a risk factor of developing severe acute respiratory disease coronavirus-2 (SARS-CoV-2) infections. Indeed, diabetes has been associated with a higher risk of infections and higher risk of developing severe forms of coronavirus disease 2019 (COVID-19) related pneumonia. Diabetic patients often present associated comorbidities such as obesity, hypertension and cardiovascular diseases, and complications of diabetes, including chronic kidney disease, vasculopathy and relative immune dysfunction, all of which make them more susceptible to infectious complications. Moreover, they often present low-grade inflammation with increased circulating interleukin levels, endothelial susceptibility to inflammation and dysfunction, and finally, hyperglycemia, which increases this risk. Additionally, corticosteroids, which count among the few medications which showed benefit on survival and mechanical ventilation requirement in COVID-19 pneumonia in large randomized controlled trials, are associated to new onsets of diabetes, and metabolic disorders in patients with previous history of diabetes. Finally, SARS-CoV-2 via the alternate effects of the renin-angiotensin system, mediated by the angiotensin-converting-enzyme 2, was also associated with insulin resistance in key tissues involved in glucose homeostasis, such as liver, skeletal muscles, and adipose tissue; and also, with impaired insulin secretion by pancreatic β-cells. In this work, we reviewed all elements which may help understand how diabetes affects patients with COVID-19, how treatments affect outcomes in patients with COVID-19, how they may cause new onsets of diabetes, and finally review how SARS-CoV-2 may inherently be a risk factor of developing diabetes, through immune-mediated diabetogenic mechanisms.
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Affiliation(s)
- Sophia Sabri
- Intensive Care Medicine, CMC Ambroise Paré, Neuilly-Sur-Seine 92200, France
| | - Olivier Bourron
- Sorbonne Université Médecine; Assistance publique Hôpitaux de Paris (APHP), Service de Diabétologie, Hôpital Pitié-Salpêtrière; INSERM UMRS_1138, Centre de recherche des Cordeliers; Institute of CArdiometabolisme and Nutrition (ICAN), Paris 75013, France
| | - Franck Phan
- Sorbonne Université Médecine; Assistance publique Hôpitaux de Paris (APHP), Service de Diabétologie, Hôpital Pitié-Salpêtrière; INSERM UMRS_1138, Centre de recherche des Cordeliers; Institute of CArdiometabolisme and Nutrition (ICAN), Paris 75013, France
| | - Lee S Nguyen
- Research and Innovation, RICAP, CMC Ambroise Paré, Neuilly-Sur-Seine 92200, France
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14
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Corona G, Pizzocaro A, Vena W, Rastrelli G, Semeraro F, Isidori AM, Pivonello R, Salonia A, Sforza A, Maggi M. Diabetes is most important cause for mortality in COVID-19 hospitalized patients: Systematic review and meta-analysis. Rev Endocr Metab Disord 2021; 22:275-296. [PMID: 33616801 PMCID: PMC7899074 DOI: 10.1007/s11154-021-09630-8] [Citation(s) in RCA: 131] [Impact Index Per Article: 32.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/20/2021] [Indexed: 12/16/2022]
Abstract
The presence of SARS-CoV-2 was officially documented in Europe at the end of February 2020. Despite many observations, the real impact of COVID-19 in the European Union (EU), its underlying factors and their contribution to mortality and morbidity outcomes were never systematically investigated. The aim of the present work is to provide an overview and a meta-analysis of main predictors and of country differences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated mortality rate (MR) in hospitalized patients. Out of 3714 retrieved articles, 87 studies were considered, including 35,486 patients (mean age 60.9 ± 8.2 years) and 5867 deaths. After adjustment for confounders, diabetes mellitus was the best predictors of MR in an age- and sex-dependent manner, followed by chronic pulmonary obstructive diseases and malignancies. In both the US and Europe, MR was higher than that reported in Asia (25[20;29] % and 20[17;23] % vs. 13[10;17]%; both p < 0.02). Among clinical parameters, dyspnea, fatigue and myalgia, along with respiratory rate, emerged as the best predictors of MR. Finally, reduced lymphocyte and platelet count, along with increased D-dimer levels, all significantly contributed to increased mortality. The optimization of glucose profile along with an adequate thrombotic complications preventive strategy must become routine practice in diseased SARS-CoV-2 infected patients.
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Affiliation(s)
- Giovanni Corona
- Endocrinology Unit, Medical Department, Azienda Usl Bologna Maggiore-Bellaria Hospital, Largo Nigrisoli, 2 - 40133, Bologna, Italy.
| | - Alessandro Pizzocaro
- Unit of Endocrinology, Diabetology and Medical Andrology, IRCSS, Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Walter Vena
- Unit of Endocrinology, Diabetology and Medical Andrology, IRCSS, Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Giulia Rastrelli
- Female Endocrinology and Gender Incongruence Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy
| | - Federico Semeraro
- Department of Anaesthesia, Intensive Care and EMS, Maggiore Hospital Bologna, Bologna, Italy
| | - Andrea M Isidori
- Department of Experimental Medicine, Sapienza University of Rome - Policlinico Umberto I Hospital, Rome, Italy
| | - Rosario Pivonello
- Dipartimento Di Medicina Clinica E Chirurgia, Sezione Di Endocrinologia, Unità Di Andrologia E Medicina Della Riproduzione E Della SessualitàMaschile E Femminile, Università Federico II Di Napoli, Naples, Italy
- Staff of UNESCO, Chair for Health Education and Sustainable Development, Federico II University, Naples, Italy
| | - Andrea Salonia
- Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Alessandra Sforza
- Endocrinology Unit, Medical Department, Azienda Usl Bologna Maggiore-Bellaria Hospital, Largo Nigrisoli, 2 - 40133, Bologna, Italy
| | - Mario Maggi
- Endocrinology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy
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15
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Lu X, Cui Z, Pan F, Li L, Li L, Liang B, Yang L, Zheng C. Glycemic status affects the severity of coronavirus disease 2019 in patients with diabetes mellitus: an observational study of CT radiological manifestations using an artificial intelligence algorithm. Acta Diabetol 2021; 58:575-586. [PMID: 33420614 PMCID: PMC7792916 DOI: 10.1007/s00592-020-01654-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 12/06/2020] [Indexed: 02/06/2023]
Abstract
AIMS Increasing evidence suggests that poor glycemic control in diabetic individuals is associated with poor coronavirus disease 2019 (COVID-19) pneumonia outcomes and influences chest computed tomography (CT) manifestations. This study aimed to explore the impact of diabetes mellitus (DM) and glycemic control on chest CT manifestations, acquired using an artificial intelligence (AI)-based quantitative evaluation system, and COVID-19 disease severity and to investigate the association between CT lesions and clinical outcome. METHODS A total of 126 patients with COVID-19 were enrolled in this retrospective study. According to their clinical history of DM and glycosylated hemoglobin (HbA1c) level, the patients were divided into 3 groups: the non-DM group (Group 1); the well-controlled blood glucose (BG) group, with HbA1c < 7% (Group 2); and the poorly controlled BG group, with HbA1c ≥ 7% (Group 3). The chest CT images were analyzed with an AI-based quantitative evaluation system. Three main quantitative CT features representing the percentage of total lung lesion volume (PLV), percentage of ground-glass opacity volume (PGV) and percentage of consolidation volume (PCV) in bilateral lung fields were used to evaluate the severity of pneumonia lesions. RESULTS Patients in Group 3 had the highest percentage of severe or critical illness, with 12 (32%) cases, followed by 6 (11%) and 7 (23%) cases in Groups 1 and 2, respectively (p = 0.042). The composite endpoints, including death or using mechanical ventilation or admission to the intensive care unit (ICU), were 3 (5%), 5 (16%) and 10 (26%) in Groups 1, 2 and 3, respectively (p = 0.013). The PLV, PGV and PCV in bilateral lung fields were significantly different among the three groups (all p < 0.001): the median PLVs were 12.5% (Group 3), 3.8% (Group 2) and 2.4% (Group 1); the median PGVs were 10.2% (Group 3), 3.6% (Group 2) and 1.9% (Group 1); and the median PCVs were 1.8% (Group 3), 0.3% (Group 2) and 0.1% (Group 1). In the linear regression analyses, which were adjusted for age, sex, BMI, and comorbidities, HbA1c remained positively associated with PLV (β = 0.401, p < 0.001), PGV (β = 0.364, p = 0.001) and PCV (β = 0.472, p < 0.001); this relationship was also observed between fasting blood glucose (FBG) and the three CT quantitative parameters. In the logistic regression analyses, PLV [OR 1.067 (1.032, 1.103)], PGV [OR 1.076 (1.034, 1.120)] and PCV [OR 1.280 (1.110, 1.476)] levels were independent predictors of the composite endpoints, as well as the areas under the ROC (AUCs) for PLV [AUC 0.796 (0.691, 0.900)], PGV [AUC 0.783 (0.678, 0.889)] and PCV [AUC 0.816 (0.722, 0.911)]; the ORs were still significant for CT lesions after adjusting for age, sex and poorly controlled diabetes. CONCLUSIONS Increased blood glucose level was correlated with the severity of lung involvement, as evidenced by certain chest CT parameters, and clinical prognosis in diabetic COVID-19 patients. There was a positive correlation between blood glucose level (both HbA1c and FBG) on admission and lung lesions. Moreover, the CT lesion severity by AI quantitative analysis was correlated with clinical outcomes.
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Affiliation(s)
- Xiaoting Lu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
| | - Zhenhai Cui
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022 China
- Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, 430022 China
| | - Feng Pan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
| | - Lingli Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
| | - Lin Li
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
| | - Bo Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
| | - Lian Yang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022 China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022 China
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16
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Moghaddam Tabrizi F, Rasmi Y, Hosseinzadeh E, Rezaei S, Balvardi M, Kouchari MR, Ebrahimi G. Diabetes is associated with higher mortality and severity in hospitalized patients with COVID-19. EXCLI JOURNAL 2021; 20:444-453. [PMID: 33746672 PMCID: PMC7975582 DOI: 10.17179/excli2021-3403] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 02/16/2021] [Indexed: 01/08/2023]
Abstract
As a novel cause of pneumonia, coronavirus disease 2019 (COVID-19) has rapidly progressed worldwide. Previous studies have indicated COVID-19 patients with diabetes show higher mortality rates and more severe COVID-19 infection with an increased requirement for intensive care and hospital length of stay (LOS) compared to non-diabetic patients. The present study aimed to investigate the association of diabetes and COVID-19 outcome with severity of disease in hospitalized patients. The present case-control study included 268 patients diagnosed with COVID-19 who were hospitalized in Ayatollah Khoyi Hospital, Khoy, Iran. Diabetes was identified based on medical history and/or criteria of published documents. Out of 268 patients (median age of 59 years; 53.4 % male), 127 patients had diabetes (47 %). Diabetic patients had remarkably higher mortality rates (adjusted odds ratio, aOR: 3.36; confidence interval, CI: 1.17-9.66), requirement for invasive mechanical ventilation (IMV) (aOR: 4.59; CI: 1.38-15.25), and LOS (aOR: 1.13; CI: 1.06-1.24) compared to patients without diabetes. Inflammatory biomarkers including C-reactive protein (CRP), lactate dehydrogenase (LDH), and erythrocyte sedimentation rate (ESR) were increased in patients with diabetes compared to non-diabetic patients (P < 0.05 for all the comparisons). In hospitalized patients with COVID-19, diabetes was correlated with increased disease severity and mortality.
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Affiliation(s)
- Fatemeh Moghaddam Tabrizi
- Reproductive Health Research Center, Urmia University of Medical Sciences, Urmia, Iran.,Khoy University of Medical Sciences, Khoy, Iran
| | - Yousef Rasmi
- Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.,Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Elyas Hosseinzadeh
- Department of Laboratory Sciences, Sirjan School of Medical Sciences, Sirjan, Iran
| | - Sakineh Rezaei
- Ayatoollah Khoyi Hospital, Khoy University of Medical Sciences, Khoy, Iran
| | - Mohadeseh Balvardi
- Instructor of Biostatistics, Sirjan School of Medical Sciences, Sirjan, Iran
| | | | - Ghasem Ebrahimi
- Department of Biochemistry and Clinical Laboratories, Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Shao S, Yang Q, Pan R, Yu X, Chen Y. Interaction of Severe Acute Respiratory Syndrome Coronavirus 2 and Diabetes. Front Endocrinol (Lausanne) 2021; 12:731974. [PMID: 34690930 PMCID: PMC8527093 DOI: 10.3389/fendo.2021.731974] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 09/17/2021] [Indexed: 01/08/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a worldwide epidemic. It spreads very fast and hits people of all ages, especially patients with underlying diseases such as diabetes. In this review, we focus on the influences of diabetes on the outcome of SARS-CoV-2 infection and the involved mechanisms including lung dysfunction, immune disorder, abnormal expression of angiotensin-converting enzyme 2 (ACE2), overactivation of mechanistic target of rapamycin (mTOR) signaling pathway, and increased furin level. On the other hand, SARS-CoV-2 may trigger the development of diabetes. It causes the damage of pancreatic β cells, which is probably mediated by ACE2 protein in the islets. Furthermore, SARS-CoV-2 may aggravate insulin resistance through attacking other metabolic organs. Of note, certain anti-diabetic drugs (OADs), such as peroxisome proliferator-activated receptor γ (PPARγ) activator and glucagon-like peptide 1 receptor (GLP-1R) agonist, have been shown to upregulate ACE2 in animal models, which may increase the risk of SARS-CoV-2 infection. However, Metformin, as a first-line medicine for the treatment of type 2 diabetes mellitus (T2DM), may be a potential drug benefiting diabetic patients with SARS-CoV-2 infection, probably via a suppression of mTOR signaling together with its anti-inflammatory and anti-fibrosis function in lung. Remarkably, another kind of OADs, dipeptidyl Peptidase 4 (DPP4) inhibitor, may also exert beneficial effects in this respect, probably via a prevention of SARS-CoV-2 binding to cells. Thus, it is of significant to identify appropriate OADs for the treatment of diabetes in the context of SARS-CoV-2 infections.
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Affiliation(s)
- Shiying Shao
- Division of Endocrinology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Hubei, China
| | - Qin Yang
- Division of Pathology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Ruping Pan
- Department of Nuclear Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Xuefeng Yu
- Division of Endocrinology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Hubei, China
| | - Yong Chen
- Division of Endocrinology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Hubei, China
- *Correspondence: Yong Chen,
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18
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Wang Y, Zhang Y, Wang K, Su Y, Zhuge J, Li W, Wang S, Yao H. Nomogram Model for Screening the Risk of Type II Diabetes in Western Xinjiang, China. Diabetes Metab Syndr Obes 2021; 14:3541-3553. [PMID: 34393494 PMCID: PMC8357405 DOI: 10.2147/dmso.s313838] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 06/29/2021] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE A simple type 2 diabetes mellitus (T2DM) screening model was established preciously based on easily available variables for identifying high-risk individuals in western Xinjiang, China. METHODS A total of 458,153 cases participating in the national health examination were recruited. Logistic regression and the least absolute shrinkage and selection operator (LASSO) models were used for univariate analysis, factors selection, and the establishment of prediction model. Receiver operating characteristic (ROC) curve, Hosmer-Lemeshow test and clinical decision curve (CDA) were applied for evaluating the discrimination, calibration and clinical validity, respectively. The optimal threshold for predicting risk factors for T2DM has been estimated as well. RESULTS The nomogram depicted the risk of T2DM based on different genders, the factors mainly consisted of age, family history of T2DM (FHOT), waist circumference (WC), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDLc), body mass index (BMI), high-density lipoprotein cholesterol (HDLc), etc. The area under ROC of men and women was 0.864 and 0.816 in the development group, similarly in the validation group, which was 0.865 and 0.815, respectively. The calibration curve showed that the nomogram was accurate for predicting the risk of T2DM, and the CDA proved great clinical application value of the nomogram. Threshold values of the age, WC, TC, TG, HDLc, BMI in different genders were 52.5 years old (men) and 48.5 years old (women), 85.50 cm (men) and 89.9 cm (women), 4.94 mmol/L (men) and 4.94mmol/L (women), 1.26mmol/L (men) and 1.67mmol/L (women), 1.40mmol/L (men) and 1.40mmol/L (women), 24.70kg/m2 (men) and 24.95kg/m2 (women), respectively. CONCLUSION Our results give a clue that the nomogram may be useful for identifying adults who have high risk for diabetes, which is simple, affordable, with high credibility and can be widely implemented. Further studies are needed to evaluate the utility and feasibility of this model in various settings.
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Affiliation(s)
- Yushan Wang
- Center of Health Management, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, People’s Republic of China
| | - Yushan Zhang
- College of Public Health, Xinjiang Medical University, Urumqi, People’s Republic of China
| | - Kai Wang
- Department of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, People’s Republic of China
| | - Yinxia Su
- Center of Health Management, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, People’s Republic of China
| | - Jinhui Zhuge
- College of Public Health, Xinjiang Medical University, Urumqi, People’s Republic of China
| | - Wenli Li
- College of Public Health, Xinjiang Medical University, Urumqi, People’s Republic of China
| | - Shuxia Wang
- Center of Health Management, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, People’s Republic of China
| | - Hua Yao
- Center of Health Management, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, People’s Republic of China
- Correspondence: Hua Yao; Shuxia Wang Center of Health Management, The First Affiliated Hospital of Xinjiang Medical University, No. 137 Liyushan South Road, Urumqi, 830011, People’s Republic of ChinaTel +86-13999180161; +86-13579901672 Email ;
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Caruso I, Giorgino F. The diabetic lung: An easy target for SARS-CoV-2? Diabetes Metab Res Rev 2020; 36:e3346. [PMID: 32426928 PMCID: PMC7267106 DOI: 10.1002/dmrr.3346] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 05/12/2020] [Indexed: 12/29/2022]
Affiliation(s)
- Irene Caruso
- Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic DiseasesUniversity of Bari Aldo MoroBariItaly
| | - Francesco Giorgino
- Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic DiseasesUniversity of Bari Aldo MoroBariItaly
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Ugwueze CV, Ezeokpo BC, Nnolim BI, Agim EA, Anikpo NC, Onyekachi KE. COVID-19 and Diabetes Mellitus: The Link and Clinical Implications. DUBAI DIABETES AND ENDOCRINOLOGY JOURNAL 2020. [PMCID: PMC7649685 DOI: 10.1159/000511354] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background Coronavirus disease 2019 (COVID-19) is a pandemic viral infection that has ravaged the world in recent times, and the associated morbidity and mortality have been much more pronounced in those with noncommunicable disease. Diabetes mellitus is one of commonest noncommunicable diseases associated with worsening clinical status in COVID-19 patients. Summary The aim of this review was to evaluate the receptors and pathogenetic link between diabetes and COVID-19. Both disease conditions involve inflammation with the release of inflammatory markers. The roles of angiotensin-converting enzyme molecule and dipeptidyl peptidase were explored to show their involvement in COVID-19 and diabetes. Pathogenetic mechanisms such as impaired immunity, microangiopathy, and glycemic variability may explain the effect of diabetes on recovery of COVID-19 patients. The effect of glucocorticoids and catecholamines, invasion of the pancreatic islet cells, drugs used in the treatment of COVID-19, and the lockdown policy may impact negatively on glycemic control of diabetic patients. The outcome studies between diabetic and nondiabetic patients with COVID-19 were also reviewed. Some drug trials are still ongoing to determine the suitability or otherwise of some drugs used in diabetic patients with COVID-19, such as dapagliflozin trial and linagliptin trial.
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Affiliation(s)
- Chidiebere V. Ugwueze
- *Chidiebere V. Ugwueze, Endocrinology, Diabetes and Metabolism Unit, Internal Medicine Department, Alex Ekwueme Federal University Teaching Hospital Abakaliki, P. M. B 102, Ben Igwenyi Street 3, Abakaliki, Ebonyi (Nigeria),
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21
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Fadini GP, Morieri ML, Boscari F, Fioretto P, Maran A, Busetto L, Bonora BM, Selmin E, Arcidiacono G, Pinelli S, Farnia F, Falaguasta D, Russo L, Voltan G, Mazzocut S, Costantini G, Ghirardini F, Tresso S, Cattelan AM, Vianello A, Avogaro A, Vettor R. Newly-diagnosed diabetes and admission hyperglycemia predict COVID-19 severity by aggravating respiratory deterioration. Diabetes Res Clin Pract 2020; 168:108374. [PMID: 32805345 PMCID: PMC7428425 DOI: 10.1016/j.diabres.2020.108374] [Citation(s) in RCA: 144] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 07/28/2020] [Accepted: 08/12/2020] [Indexed: 02/06/2023]
Abstract
AIMS We investigated whether pre-existing diabetes, newly-diagnosed diabetes, and admission hyperglycemia were associated with COVID-19 severity independently from confounders. METHODS We retrospectively analyzed data on patients with COVID-19 hospitalized between February and April 2020 in an outbreak hospital in North-East Italy. Pre-existing diabetes was defined by self-reported history, electronic medical records, or ongoing medications. Newly-diagnosed diabetes was defined by HbA1c and fasting glucose. The primary outcome was a composite of ICU admission or death. RESULTS 413 subjects were included, 107 of whom (25.6%) had diabetes, including 21 newly-diagnosed. Patients with diabetes were older and had greater comorbidity burden. The primary outcome occurred in 37.4% of patients with diabetes compared to 20.3% in those without (RR 1.85; 95%C.I. 1.33-2.57; p < 0.001). The association was stronger for newly-diagnosed compared to pre-existing diabetes (RR 3.06 vs 1.55; p = 0.004). Higher glucose level at admission was associated with COVID-19 severity, with a stronger association among patients without as compared to those with pre-existing diabetes (interaction p < 0.001). Admission glucose was correlated with most clinical severity indexes and its association with adverse outcome was mostly mediated by a worse respiratory function. CONCLUSION Newly-diagnosed diabetes and admission hyperglycemia are powerful predictors of COVID-19 severity due to rapid respiratory deterioration.
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Affiliation(s)
| | | | | | | | | | - Luca Busetto
- Department of Medicine, University of Padova, Italy
| | | | - Elisa Selmin
- Department of Medicine, University of Padova, Italy
| | | | | | | | | | - Lucia Russo
- Department of Medicine, University of Padova, Italy
| | | | | | | | | | | | | | - Andrea Vianello
- Department of Cardiothoracic Vascular Sciences and Public Health, University of Padova, Italy
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22
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Mantovani A, Byrne CD, Zheng MH, Targher G. Diabetes as a risk factor for greater COVID-19 severity and in-hospital death: A meta-analysis of observational studies. Nutr Metab Cardiovasc Dis 2020; 30:1236-1248. [PMID: 32571616 PMCID: PMC7258796 DOI: 10.1016/j.numecd.2020.05.014] [Citation(s) in RCA: 186] [Impact Index Per Article: 37.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 05/23/2020] [Accepted: 05/25/2020] [Indexed: 02/07/2023]
Abstract
AIMS To estimate the prevalence of established diabetes and its association with the clinical severity and in-hospital mortality associated with COVID-19. DATA SYNTHESIS We systematically searched PubMed, Scopus and Web of Science, from 1st January 2020 to 15th May 2020, for observational studies of patients admitted to hospital with COVID-19. Meta-analysis was performed using random-effects modeling. A total of 83 eligible studies with 78,874 hospitalized patients with laboratory-confirmed COVID-19 were included. The pooled prevalence of established diabetes was 14.34% (95% CI 12.62-16.06%). However, the prevalence of diabetes was higher in non-Asian vs. Asian countries (23.34% [95% CI 16.40-30.28] vs. 11.06% [95% CI 9.73-12.39]), and in patients aged ≥60 years vs. those aged <60 years (23.30% [95% CI 19.65-26.94] vs. 8.79% [95% CI 7.56-10.02]). Pre-existing diabetes was associated with an approximate twofold higher risk of having severe/critical COVID-19 illness (n = 22 studies; random-effects odds ratio 2.10, 95% CI 1.71-2.57; I2 = 41.5%) and ~threefold increased risk of in-hospital mortality (n = 15 studies; random-effects odds ratio 2.68, 95% CI 2.09-3.44; I2 = 46.7%). Funnel plots and Egger's tests did not reveal any significant publication bias. CONCLUSIONS Pre-existing diabetes is significantly associated with greater risk of severe/critical illness and in-hospital mortality in patients admitted to hospital with COVID-19.
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Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
| | - Christopher D Byrne
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Ming-Hua Zheng
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
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23
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Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J, Lei F, Wang H, Xie J, Wang W, Li H, Zhang P, Song X, Chen X, Xiang M, Zhang C, Bai L, Xiang D, Chen MM, Liu Y, Yan Y, Liu M, Mao W, Zou J, Liu L, Chen G, Luo P, Xiao B, Zhang C, Zhang Z, Lu Z, Wang J, Lu H, Xia X, Wang D, Liao X, Peng G, Ye P, Yang J, Yuan Y, Huang X, Guo J, Zhang BH, Li H. Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes. Cell Metab 2020; 31:1068-1077.e3. [PMID: 32369736 PMCID: PMC7252168 DOI: 10.1016/j.cmet.2020.04.021] [Citation(s) in RCA: 1093] [Impact Index Per Article: 218.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 04/26/2020] [Accepted: 04/28/2020] [Indexed: 02/08/2023]
Abstract
Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.
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Affiliation(s)
- Lihua Zhu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China; Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Zhi-Gang She
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China; Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Xu Cheng
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China; Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Juan-Juan Qin
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China; Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Xiao-Jing Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China; Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Jingjing Cai
- Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha 410000, China
| | - Fang Lei
- Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Haitao Wang
- Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Jing Xie
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China
| | - Wenxin Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China; Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Haomiao Li
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China; Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Peng Zhang
- Institute of Model Animal, Wuhan University, Wuhan 430072, China; Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Xiaohui Song
- Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Xi Chen
- Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Mei Xiang
- Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430072, China
| | - Chaozheng Zhang
- Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Liangjie Bai
- Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Da Xiang
- Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Ming-Ming Chen
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China; Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Yanqiong Liu
- Institute of Model Animal, Wuhan University, Wuhan 430072, China
| | - Youqin Yan
- Wuhan Seventh Hospital, Wuhan 430072, China
| | - Mingyu Liu
- The Ninth Hospital of Wuhan City, Wuhan 430072, China
| | - Weiming Mao
- Department of General Surgery, Huanggang Central Hospital, Huanggang 438000, China
| | - Jinjing Zou
- Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430072, China
| | - Liming Liu
- Department of General Surgery, Ezhou Central Hospital, Ezhou 436000, China
| | - Guohua Chen
- Department of Neurology, Wuhan First Hospital/Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan 430072, China
| | - Pengcheng Luo
- Department of Urology, Wuhan Third Hospital and Tongren Hospital of Wuhan University, Wuhan 430072, China
| | - Bing Xiao
- Department of Stomatology, Xiantao First People's Hospital, Xiantao 433000, China
| | - Changjiang Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China; The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China
| | - Zixiong Zhang
- The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China
| | - Zhigang Lu
- Department of Neurology, The First People's Hospital of Jingmen affiliated to Hubei Minzu University, Jingmen 448000, China
| | - Junhai Wang
- Department of Orthopedics, The First People's Hospital of Jingmen affiliated to Hubei Minzu University, Jingmen 448000 China
| | - Haofeng Lu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Changjiang University, Jingzhou 434000, China
| | - Xigang Xia
- Department of Hepatobiliary Surgery, Jingzhou Central Hospital, Jingzhou 434000, China
| | - Daihong Wang
- Department of Hepatobiliary and Pancreatic Surgery, Xianning Central Hospital, Xianning 437000, China
| | - Xiaofeng Liao
- Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441000, China
| | - Gang Peng
- Department of Hepatobiliary and Pancreatic Surgery, Suizhou Central Hospital Affiliated to Hubei Medical College, Suizhou 441300, China
| | - Ping Ye
- Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430072, China
| | - Jun Yang
- Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People's Hospital and Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, China
| | - Yufeng Yuan
- Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Xiaodong Huang
- Department of Gastroenterology, Wuhan Third Hospital and Tongren Hospital of Wuhan University, Wuhan 430072, China.
| | - Jiao Guo
- Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine & Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China and Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, China.
| | - Bing-Hong Zhang
- Department of Neonatology, Renmin Hospital of Wuhan University, Wuhan 430072, China.
| | - Hongliang Li
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China; Institute of Model Animal, Wuhan University, Wuhan 430072, China; Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430072, China; Basic Medical School, Wuhan University, Wuhan 430072, China.
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Diabetes and severity of COVID-19: What is the link? Med Hypotheses 2020; 143:109923. [PMID: 32485315 PMCID: PMC7260494 DOI: 10.1016/j.mehy.2020.109923] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 05/28/2020] [Indexed: 12/04/2022]
Abstract
In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.
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25
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Impact of type 2 diabetes mellitus on mid-term mortality for hypertrophic cardiomyopathy patients who underwent septal myectomy. Cardiovasc Diabetol 2020; 19:64. [PMID: 32404127 PMCID: PMC7222568 DOI: 10.1186/s12933-020-01036-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 05/07/2020] [Indexed: 01/15/2023] Open
Abstract
Background Type 2 diabetes mellitus is common in cardiovascular disease. It is associated with adverse clinical outcomes for patients who had undergone coronary artery bypass and valve operations. The aim of this study was to evaluate the impact of type 2 diabetes mellitus on the midterm outcomes of patients with hypertrophic cardiomyopathy who underwent septal myectomy. Methods We retrospectively analyzed the data of 67 hypertrophic cardiomyopathy patients with type 2 diabetes mellitus who underwent septal myectomy from two medical centers in China from 2011 to 2018. A propensity score–matched cohort of 134 patients without type 2 diabetes mellitus was also analyzed. Results During a median follow-up of 28.0 (interquartile range: 13.0–3.0) months, 9 patients died. The cause of death of all of these patients was cardiovascular, particularly sudden cardiac death in 3 patients. Patients with type 2 diabetes mellitus had a higher rate of sudden cardiac death (4.5% vs. 0.0%, p = 0.04). The Kaplan–Meier survival analysis revealed that the rates of predicted 3-year survival free from cardiovascular death (98.1% vs. 95.1%, p = 0.14) were similar between the two groups. However, the rates of predicted 3-year survival free from sudden cardiac death (100% vs. 96.7%, p = 0.01) were significantly higher in hypertrophic cardiomyopathy patients without type 2 diabetes mellitus than in those with type 2 diabetes mellitus. Furthermore, after adjustment for age and sex, only N-terminal pro-brain natriuretic peptide (hazards ratio: 1.002, 95% confidence interval: 1.000–1.005, p = 0.02) and glomerular filtration rate ≤ 80 ml/min (hazards ratio: 3.23, 95% confidence interval: 1.34–7.24, p = 0.047) were independent risk factors for hypertrophic cardiomyopathy patients with type 2 diabetes mellitus. Conclusions Hypertrophic cardiomyopathy patients with and without type 2 diabetes mellitus have similar 3-year cardiovascular mortality after septal myectomy. However, type 2 diabetes mellitus is associated with higher sudden cardiac death rate in these patients. In addition, N-terminal pro-brain natriuretic peptide and glomerular filtration rate ≤ 80 ml/min were independent risk factors among hypertrophic cardiomyopathy patients with type 2 diabetes mellitus.
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Lin Z, Guo D, Chen J, Zheng B. A nomogram for predicting 5-year incidence of type 2 diabetes in a Chinese population. Endocrine 2020; 67:561-568. [PMID: 31820309 DOI: 10.1007/s12020-019-02154-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Accepted: 11/27/2019] [Indexed: 02/08/2023]
Abstract
PURPOSE To develop a nomogram for predicting 5-year incidence of type 2 diabetes (T2D) in Chinese adults. METHODS This is a retrospective cohort study from a prospectively collected database. We included a total 32,766 adults free of T2D at baseline with a median follow-up of 3 years. Univariate and multivariate Cox regression analyses were applied to identify independent predictors. A nomogram was constructed to predict 5-year incident rate of T2D based on the multivariate analysis results. Harrell's C-indexes and calibration plots were used to evaluate the accuracy of the nomogram in both internal and external validations. RESULTS The overall prevalence of T2D was 2.1%. Participants were randomly divided into a training set (n = 21,844) and a validation set (n = 10,922). After multivariate analysis in the training set, age, sex, BMI, hypertension, dyslipidemia, smoking status, and family history were found as risk predictors and integrated into the nomogram. Harrell's C-indexes were 0.815 (95% CI: 0.797-0.834) and 0.779 (95% CI: 0.747-0.811) in the training and validation sets, respectively. The calibration plots demonstrated good agreement between the estimated probability and the actual observation. CONCLUSION Our nomogram could be a simple and reliable tool for predicting 5-year risk of developing T2D in high-risk Chinese. Through the model, early identifying high-risk individuals is helpful for timely intervention to reduce the incidence of T2D.
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Affiliation(s)
- Zeyin Lin
- Department of Ultrasound, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Dongming Guo
- Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Juntian Chen
- Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Baoqun Zheng
- Department of Ultrasound, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
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Fadini GP, Albiero M, Bonora BM, Avogaro A. Angiogenic Abnormalities in Diabetes Mellitus: Mechanistic and Clinical Aspects. J Clin Endocrinol Metab 2019; 104:5431-5444. [PMID: 31211371 DOI: 10.1210/jc.2019-00980] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 06/12/2019] [Indexed: 12/25/2022]
Abstract
CONTEXT Diabetes causes severe pathological changes to the microvasculature in many organs and tissues and is at the same time associated with an increased risk of coronary and peripheral macrovascular events. We herein review alterations in angiogenesis observed in human and experimental diabetes and how they contribute to diabetes onset and development of vascular complications. EVIDENCE ACQUISITION The English language medical literature was searched for articles reporting on angiogenesis/vasculogenesis abnormalities in diabetes and their clinical manifestations, mechanistic aspects, and possible therapeutic implications. EVIDENCE SYNTHESIS Angiogenesis is a complex process, driven by a multiplicity of molecular mechanisms and involved in several physiological and pathological conditions. Incompetent angiogenesis is pervasive in diabetic vascular complications, with both excessive and defective angiogenesis observed in various tissues. A striking different angiogenic response typically occurs in the retina vs the myocardium and peripheral circulation, but some commonalities in abnormal angiogenesis can explain the well-known association between microangiopathy and macroangiopathy. Impaired angiogenesis can also affect endocrine islet and adipose tissue function, providing a link to diabetes onset. Exposure to high glucose itself directly affects angiogenic/vasculogenic processes, and the mechanisms include defective responses to hypoxia and proangiogenic factors, impaired nitric oxide bioavailability, shortage of proangiogenic cells, and loss of pericytes. CONCLUSIONS Dissecting the molecular drivers of tissue-specific alterations of angiogenesis/vasculogenesis is an important challenge to devise new therapeutic approaches. Angiogenesis-modulating therapies should be carefully evaluated in view of their potential off-target effects. At present, glycemic control remains the most reasonable therapeutic strategy to normalize angiogenesis in diabetes.
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Affiliation(s)
- Gian Paolo Fadini
- Department of Medicine, University of Padova, Padova, Italy
- Venetian Institute of Molecular Medicine, Padova, Italy
| | - Mattia Albiero
- Department of Medicine, University of Padova, Padova, Italy
- Venetian Institute of Molecular Medicine, Padova, Italy
| | - Benedetta Maria Bonora
- Department of Medicine, University of Padova, Padova, Italy
- Venetian Institute of Molecular Medicine, Padova, Italy
| | - Angelo Avogaro
- Department of Medicine, University of Padova, Padova, Italy
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Tian CJ, Zhen Z. Reactive Carbonyl Species: Diabetic Complication in the Heart and Lungs. Trends Endocrinol Metab 2019; 30:546-556. [PMID: 31253519 DOI: 10.1016/j.tem.2019.05.005] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 05/26/2019] [Accepted: 05/28/2019] [Indexed: 12/28/2022]
Abstract
Abnormal chemical reactions in hyperglycemia alter normal metabolic processes in diabetes, which is a key process in the production of reactive carbonyls species (RCS). Increasing the concentration of RCS may result in carbonyl/oxidative stress in both the diabetic heart and lung. Ryanodine receptors (RyRs) not only play a key role in heart contraction, including rhythmic contraction and relaxation of the heart, but they are also important for controlling the airway smooth muscle. RCS modifies RyRs, resulting in RyRs dysfunction, which is involved in important mechanisms in diabetic complications. Very little is known about the mechanistic relationship between the heart and lung in diabetes. This review highlights new findings on the pathophysiological mechanisms and discusses potential approaches to treatment for these complications.
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Affiliation(s)
- Cheng-Ju Tian
- College of Rehabilitation and Sports Medicine, Jinzhou Medical University, Jinzhou, Liaoning, 121001, China.
| | - Zhong Zhen
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
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