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Lawand JJ, Tansey PJ, Ghali A, Tye C, Hantouly A, Fares MY, Khan AZ, Somerson JS, Abboud JA. Glucagon-like peptide-1 receptor agonist use is associated with increased risk of perioperative complication and readmission following shoulder arthroplasty. J Shoulder Elbow Surg 2025; 34:1152-1157. [PMID: 39528042 DOI: 10.1016/j.jse.2024.09.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 08/15/2024] [Accepted: 09/01/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Glucagon-like peptide-1 (GLP-1) receptor agonists, increasingly used for diabetes management and weight loss, have been linked to lower readmission rates after knee and hip arthroplasty. However, their impact on total shoulder arthroplasty (TSA) outcomes remains unclear. This study investigates the effects of GLP-1 receptor agonists on major complications and revisions following TSA. METHODS A retrospective query of the TriNetX database from 2010 to 2023 was performed to identify patients who underwent anatomic or reverse TSA and were prescribed GLP-1 receptor agonists. GLP-1 receptor agonist users were 1:1 propensity score-matched to controls for demographic factors and comorbidities, yielding 1259 patients in each group. Outcomes included 90-day postoperative medical complications and readmission and revision surgery at 2 years. Odds ratios (ORs), 95% confidence intervals, and P values were calculated. After Bonferroni correction, P < .005 was considered significant. RESULTS GLP-1 receptor agonist users (n = 1259) experienced significantly higher rates of deep vein thrombosis (1.6% vs. 0.9%; OR 3.0; P = .001), myocardial infarction (1.60% vs. 0.9%; OR 2.84; P = .003), pneumonia (3.34% vs. 1.50%; OR 2.25; P = .003), transfusion (7.1% vs. 4.3%; OR 1.7; P = .003), and readmission (8.1% vs. 5.2%; OR 1.6; P = .004) in the 90-day postoperative period compared to patients not taking GLP-1 receptor agonists. There were no differences in the rates of stroke, pulmonary embolism, postoperative anemia, or renal failure. In patients with a minimum 2-year follow-up (n = 776), there was no difference in revision rate (3.2% vs. 1.8%; OR 1.8; P = .07). CONCLUSION GLP-1 receptor agonist use during TSA was associated with an increased risk of deep vein thrombosis, myocardial infarction, pneumonia, need for transfusion, and readmission. Further investigation into the perioperative risk assessment and medical optimization of patients utilizing GLP-1 receptor agonists may be warranted.
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Affiliation(s)
- Jad J Lawand
- John Sealy School of Medicine, The University of Texas Medical Branch, Galveston, TX, USA.
| | - Patrick J Tansey
- Department of Orthopaedic Surgery and Rehabilitation, The University of Texas Medical Branch, Galveston, TX, USA
| | - Abdullah Ghali
- Department of Orthopaedics, Baylor College of Medicine, Houston, TX, USA
| | - Cooper Tye
- Department of Orthopaedic Surgery, John Peter Smith Hospital, Fort Worth, TX, USA
| | - Ashraf Hantouly
- Department of Orthopedic Surgery, Hamad Medical Corporation, Doha, Qatar
| | - Mohamad Y Fares
- Division of Shoulder and Elbow Surgery, Rothman Orthopaedic Institute, Philadelphia, PA, USA
| | - Adam Z Khan
- Department of Orthopaedic Surgery, Southern California Permanente Medical Group, Panorama City, CA, USA
| | - Jeremy S Somerson
- Department of Orthopaedic Surgery and Rehabilitation, The University of Texas Medical Branch, Galveston, TX, USA
| | - Joseph A Abboud
- Division of Shoulder and Elbow Surgery, Rothman Orthopaedic Institute, Philadelphia, PA, USA
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Mirghani HO. Platelets indices clinical implications in diabetes mellitus: A broader insight. World J Diabetes 2025; 16:100467. [PMID: 40236869 PMCID: PMC11947906 DOI: 10.4239/wjd.v16.i4.100467] [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: 08/19/2024] [Revised: 01/06/2025] [Accepted: 01/17/2025] [Indexed: 02/28/2025] Open
Abstract
Platelet indices (PIs) including high mean platelet volume (MPV), plateletcrit (PLC), and platelet distribution width (PLDW) are associated with poor glycemic control. In addition, they can indicate prothrombotic and procoagulation risk among patients with diabetes. PI measurement is cheap, quick and fits healthcare system needs in remote outreaching areas in low-income countries. However, a broader insight into their clinical implications in diabetes is lacking. To achieve a wider understanding, we reviewed PubMed/MEDLINE, Google Scholar and Cochrane Library for relevant articles investigating the role of PIs in diabetes mellitus. No limitation to the publication date was applied, which included all articles published up to August 17, 2024. The terms used were MPV, PLC, PLDW, platelet large cell ratio, glycated hemoglobin (HbA1c), PIs, platelet activity and diabetes mellitus. Out of the 790 articles retrieved, 187 full texts were reviewed, and 44 were included. PIs, when measurements are done promptly and within 2 h, could be short-term pointers to glycemic control in the life span of the platelets (2 wk). PIs are easy to perform, cheap and useful in remote outreaching areas with limited facilities where measurement of HbA1c is not available or cost-effective. However, PIs are not specific and are affected by demographic factors, such as pregnancy, renal failure, medications, hemoglobin and duration of diabetes. PIs could be implemented with daily blood glucose to inform doctors in low-income countries about their patients' glycemic control and cardiovascular risk. An important application might be when blood glucose control is needed quickly (before elective surgery).
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Lin C, Chen J, Meyerowitz‐Katz G, Huang Y, Su P. Unexpected cardiovascular risks of glucagon-like peptide-1 receptor agonist and aspirin co-administration in individuals with obesity, with and without type 2 diabetes: A propensity score matched cohort study. Diabetes Obes Metab 2025; 27:1980-1991. [PMID: 39806559 PMCID: PMC11885080 DOI: 10.1111/dom.16191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 12/16/2024] [Accepted: 12/30/2024] [Indexed: 01/16/2025]
Abstract
AIMS To examine the cardiovascular safety of combining glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with aspirin in individuals with obesity, both with and without type 2 diabetes (T2D). MATERIALS AND METHODS This propensity score matched cohort study analysed data from 2 946 579 individuals with obesity, with and without T2D, using the TriNetX US and Global dataset. Participants were categorized into four matched groups: those receiving GLP-1 RA plus aspirin versus those receiving GLP-1 RA alone, for both diabetic and non-diabetic individuals. Cardiovascular outcomes and adverse events were evaluated over 5 years using Cox proportional hazards models. RESULTS Individuals with obesity treated with GLP-1 RAs plus aspirin showed significantly higher risks of various cardiovascular events compared to those on GLP-1 RAs alone. In non-diabetic obese individuals, the combination therapy increased risks of hypertensive heart diseases (HR 1.40, 95% CI 1.15-1.60), ischaemic heart disease (HR 2.39, 95% CI 1.92-2.97) and heart failure (HR 1.97, 95% CI 1.54-2.53). Similar patterns were observed in individuals with T2D. Atrial fibrillation and cardiac arrhythmias showed increasing hazard ratios over time. The combination therapy also led to more frequent adverse events, including gastrointestinal bleeding. CONCLUSIONS The combination of GLP-1 RAs with aspirin in individuals with obesity, both with and without T2D, was associated with increased cardiovascular risks compared to GLP-1 RA monotherapy. These findings suggest that there may be risks associated with the combined use of these treatments and highlight the need for further research into this possible complication with regard to treatment.
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Affiliation(s)
- Chia‐Ming Lin
- Department of PediatricsChung Shan Medical University HospitalTaichungTaiwan
- School of MedicineChung Shan Medical UniversityTaichungTaiwan
| | - Jo‐Ching Chen
- Department of PediatricsChung Shan Medical University HospitalTaichungTaiwan
- School of MedicineChung Shan Medical UniversityTaichungTaiwan
| | | | - Yu‐Nan Huang
- Department of PediatricsChung Shan Medical University HospitalTaichungTaiwan
- School of MedicineChung Shan Medical UniversityTaichungTaiwan
| | - Pen‐Hua Su
- Department of PediatricsChung Shan Medical University HospitalTaichungTaiwan
- School of MedicineChung Shan Medical UniversityTaichungTaiwan
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Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med 2025; 31:951-962. [PMID: 39833406 DOI: 10.1038/s41591-024-03412-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 11/12/2024] [Indexed: 01/22/2025]
Abstract
Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are increasingly being used to treat diabetes and obesity. However, their effectiveness and risks have not yet been systematically evaluated in a comprehensive set of possible health outcomes. Here, we used the US Department of Veterans Affairs databases to build a cohort of people with diabetes who initiated GLP-1RA (n = 215,970) and compared them to those who initiated sulfonylureas (n = 159,465), dipeptidyl peptidase 4 (DPP4) inhibitors (n = 117,989) or sodium-glucose cotransporter-2 (SGLT2) inhibitors (n = 258,614), a control group composed of an equal proportion of individuals initiating sulfonylureas, DPP4 inhibitors and SGLT2 inhibitors (n = 536,068), and a control group of 1,203,097 individuals who continued use of non-GLP-1RA antihyperglycemics (usual care). We used a discovery approach to systematically map an atlas of the associations of GLP-1RA use versus each comparator with 175 health outcomes. Compared to usual care, GLP-1RA use was associated with a reduced risk of substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer's disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions. There was an increased risk of gastrointestinal disorders, hypotension, syncope, arthritic disorders, nephrolithiasis, interstitial nephritis and drug-induced pancreatitis associated with GLP-1RA use compared to usual care. The results provide insights into the benefits and risks of GLP-1RAs and may be useful for informing clinical care and guiding research agendas.
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Affiliation(s)
- Yan Xie
- Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO, USA
- Veterans Research and Education Foundation of St. Louis, St. Louis, MO, USA
- Division of Pharmacoepidemiology, Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO, USA
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - Taeyoung Choi
- Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO, USA
- Veterans Research and Education Foundation of St. Louis, St. Louis, MO, USA
| | - Ziyad Al-Aly
- Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO, USA.
- Veterans Research and Education Foundation of St. Louis, St. Louis, MO, USA.
- Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
- Nephrology Section, Medicine Service, VA St. Louis Health Care System, St. Louis, MO, USA.
- Institute for Public Health, Washington University in St. Louis, St. Louis, MO, USA.
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Li L, Liu S, Tan J, Wei L, Wu D, Gao S, Weng Y, Chen J. Recent advance in treatment of atherosclerosis: Key targets and plaque-positioned delivery strategies. J Tissue Eng 2022; 13:20417314221088509. [PMID: 35356091 PMCID: PMC8958685 DOI: 10.1177/20417314221088509] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Atherosclerosis, a chronic inflammatory disease of vascular wall, is a progressive pathophysiological process with lipids oxidation/depositing initiation and innate/adaptive immune responses. The coordination of multi systems covering oxidative stress, dysfunctional endothelium, diseased lipid uptake, cell apoptosis, thrombotic and pro-inflammatory responding as well as switched SMCs contributes to plaque growth. In this circumstance, inevitably, targeting these processes is considered to be effective for treating atherosclerosis. Arriving, retention and working of payload candidates mediated by targets in lesion direct ultimate therapeutic outcomes. Accumulating a series of scientific studies and clinical practice in the past decades, lesion homing delivery strategies including stent/balloon/nanoparticle-based transportation worked as the potent promotor to ensure a therapeutic effect. The objective of this review is to achieve a very brief summary about the effective therapeutic methods cooperating specifical targets and positioning-delivery strategies in atherosclerosis for better outcomes.
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Affiliation(s)
- Li Li
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Sainan Liu
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Jianying Tan
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Lai Wei
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Dimeng Wu
- Chengdu Daxan Innovative Medical Tech. Co., Ltd., Chengdu, PR China
| | - Shuai Gao
- Chengdu Daxan Innovative Medical Tech. Co., Ltd., Chengdu, PR China
| | - Yajun Weng
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
| | - Junying Chen
- Key Laboratory of Advanced Technology of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu, PR China
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Alshanwani A, Kashour T, Badr A. Anti-Diabetic Drugs GLP-1 Agonists and DPP-4 Inhibitors may Represent Potential Therapeutic Approaches for COVID-19. Endocr Metab Immune Disord Drug Targets 2022; 22:571-578. [PMID: 34370655 DOI: 10.2174/1871530321666210809153558] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 05/24/2021] [Accepted: 05/26/2021] [Indexed: 01/08/2023]
Abstract
The fast spread of coronavirus 2019 (COVID-19) calls for immediate action to counter the associated significant loss of human life and deep economic impact. Certain patient populations like those with obesity and diabetes are at higher risk for acquiring severe COVID-19 disease and have a higher risk of COVID-19 associated mortality. In the absence of an effective and safe vaccine, the only immediate promising approach is to repurpose an existing approved drug. Several drugs have been proposed and tested as adjunctive therapy for COVID-19. Among these drugs are the glucagon-like peptide-1 (GLP-1) 2 agonists and the dipeptidylpeptidase-4 (DPP-4) inhibitors. Beyond their glucose-lowering effects, these drugs have several pleiotropic protective properties, which include cardioprotective effects, anti-inflammatory and immunomodulatory activities, antifibrotic effects, antithrombotic effects, and vascular endothelial protective properties. This narrative review discusses these protective properties and addresses their scientific plausibility for their potential use as adjunctive therapy for COVID-19 disease.
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Affiliation(s)
- Aliah Alshanwani
- College of Medicine, Physiology Department, King Saud University, Riyadh, Saudi Arabia
| | - Tarek Kashour
- King Fahd Cardiac Centre, King Saud University Medical City, Riyadh, Saudi Arabia
| | - Amira Badr
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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Zhang Y, Chen R, Jia Y, Chen M, Shuai Z. Effects of Exenatide on Coagulation and Platelet Aggregation in Patients with Type 2 Diabetes. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:3027-3040. [PMID: 34285470 PMCID: PMC8285923 DOI: 10.2147/dddt.s312347] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 06/16/2021] [Indexed: 12/25/2022]
Abstract
Objective To explore the effect of the glucagon-like peptide-1 receptor agonist exenatide on coagulation function and platelet aggregation in patients with type 2 diabetes mellitus (T2DM). Methods Thirty patients with newly diagnosed T2DM were enrolled as the case group, and 30 healthy people with matching age and sex were selected as the control group. Patients in the case group received exenatide treatment for 8 weeks. The general clinical data and biochemical indicators of all subjects were collected; and their peripheral blood platelet count, coagulation index, nitric oxide (NO), platelet membrane glycoprotein (CD62p), platelet activation complex-1 (PAC-1) and platelet aggregation induced by collagen, epinephrine (EPI), arachidonic acid (AA), and adenosine diphosphate (ADP) were detected. Results The fibrinogen, CD62p, PAC-1, and platelet aggregation rates of the case group (pretreatment) are higher than those in the control group (EPI 77.90±6.31 vs 60.15±5.37, ADP 52.89±9.36 vs 47.90±6.16, and AA 76.09±3.14 vs.55.18±3.55); and the NO level is lower in the case group than in the control group (p<0.05, respectively). After 8 weeks of exenatide treatment in the case group, the CD62p, PAC-1, and platelet aggregation rates were lower than before the treatment (EPI: 61.96±8.94 vs 77.90±6.31 and AA: 50.98±6.73 vs 76.09±3.14); and the NO level was higher than before the treatment (p<0.05, respectively). Pearson correlation analysis showed that the changes in platelet aggregation rates (Δ EPI and ΔAA) of the patients in the case group after 8 weeks of exenatide treatment were positively correlated with the changes in body mass index, waist circumference, weight, blood lipids, fasting plasma glucose, haemoglobin A1c, fibrinogen, CD62p, and PAC-1 and negatively correlated with the changes in high-density lipoprotein and NO (p<0.05). Multiple linear regression analysis showed that the changes in NO, CD62p and PAC-1 were independent risk factors affecting the changes in platelet aggregation rates. Conclusion The GLP-1R agonist exenatide can inhibit the activation state of platelets in patients with T2DM and inhibit thrombosis, which is beneficial to reduce the risk of cardiovascular events.
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Affiliation(s)
- Yaqin Zhang
- Department of Rheumatology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China
| | - Ruofei Chen
- Department of Rheumatology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China
| | - Yangyang Jia
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China
| | - Mingwei Chen
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China
| | - Zongwen Shuai
- Department of Rheumatology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China
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Helmstädter J, Keppeler K, Küster L, Münzel T, Daiber A, Steven S. Glucagon-like peptide-1 (GLP-1) receptor agonists and their cardiovascular benefits-The role of the GLP-1 receptor. Br J Pharmacol 2021; 179:659-676. [PMID: 33764504 PMCID: PMC8820186 DOI: 10.1111/bph.15462] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 03/12/2021] [Accepted: 03/18/2021] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular outcome trials revealed cardiovascular benefits for type 2 diabetes mellitus patients when treated with long‐acting glucagon‐like peptide‐1 (GLP‐1) receptor agonists. In the last decade, major advances were made characterising the physiological effects of GLP‐1 and its action on numerous targets including brain, liver, kidney, heart and blood vessels. However, the effects of GLP‐1 and receptor agonists, and the GLP‐1 receptor on the cardiovascular system have not been fully elucidated. We compare results from cardiovascular outcome trials of GLP‐1 receptor agonists and review pleiotropic clinical and preclinical data concerning cardiovascular protection beyond glycaemic control. We address current knowledge on GLP‐1 and receptor agonist actions on the heart, vasculature, inflammatory cells and platelets, and discuss evidence for GLP‐1 receptor‐dependent versus independent effects secondary of GLP‐1 metabolites. We conclude that the favourable cardiovascular profile of GLP‐1 receptor agonists might expand their therapeutic use for treating cardiovascular disease even in non‐diabetic populations.
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Affiliation(s)
- Johanna Helmstädter
- Department of Cardiology, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Karin Keppeler
- Department of Cardiology, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Leonie Küster
- Department of Cardiology, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Thomas Münzel
- Department of Cardiology, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.,Center of Thrombosis and Hemostasis (CTH), University Medical Center, Mainz, Germany.,Partner Site Rhine-Main, German Center for Cardiovascular Research (DZHK), Mainz, Germany
| | - Andreas Daiber
- Department of Cardiology, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.,Center of Thrombosis and Hemostasis (CTH), University Medical Center, Mainz, Germany.,Partner Site Rhine-Main, German Center for Cardiovascular Research (DZHK), Mainz, Germany
| | - Sebastian Steven
- Department of Cardiology, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.,Center of Thrombosis and Hemostasis (CTH), University Medical Center, Mainz, Germany
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Yaribeygi H, Atkin SL, Jamialahmadi T, Sahebkar A. A Review on the Effects of New Anti-Diabetic Drugs on Platelet Function. Endocr Metab Immune Disord Drug Targets 2021; 20:328-334. [PMID: 31612835 DOI: 10.2174/1871530319666191014110414] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 08/05/2019] [Accepted: 09/13/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Cardiovascular complications account for the majority of deaths caused by diabetes mellitus. Platelet hyperactivity has been shown to increase the risk of thrombotic events and is a therapeutic target for their prevention in diabetes. Modulation of platelet function by diabetes agents in addition to their hypoglycemic effects would contribute to cardiovascular protection. Newly introduced antidiabetic drugs of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors may have anti-platelet effects, and in the case of SGLT2i and GLP-1RA may contribute to their proven cardiovascular benefit that has been shown clinically. OBJECTIVE Here, we reviewed the potential effects of these agents on platelet function in diabetes. RESULTS AND CONCLUSION GLP-1RA and DPP-4i drugs have antiplatelet properties beyond their primary hypoglycemic effects. Whilst we have little direct evidence for the antiplatelet effects of SGLT2 inhibitors, some studies have shown that these agents may inhibit platelet aggregation and reduce the risk of thrombotic events in diabetes.
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Affiliation(s)
- Habib Yaribeygi
- Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran
| | | | - Tannaz Jamialahmadi
- Halal Research Center of IRI, FDA, Tehran, Iran.,Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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10
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Yamashita Y, Sakakibara H, Toda T, Ashida H. Insights into the potential benefits of black soybean ( Glycine max L.) polyphenols in lifestyle diseases. Food Funct 2020; 11:7321-7339. [PMID: 32852022 DOI: 10.1039/d0fo01092h] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Black soybean (Glycine max L.), a cultivar containing abundant polyphenols in its seed coat such as anthocyanins and flavan-3-ols, has been reported to possess various health benefits toward lifestyle diseases. In this review article, the safety evaluation of polyphenol-rich black soybean seed coat extract (BE) and absorption of BE polyphenols are summarized. Additionally, we describe the antioxidant activity of BE polyphenols and their ability to induce antioxidant enzymes. The health benefits of BE and its polyphenols, such as anti-obesity and anti-hyperglycemic activities through the activation of AMP-activated protein kinase and translocation of glucose transporter 4, respectively, are also discussed. Furthermore, we found that black soybean polyphenols were involved in the improvement of vascular function. These emerging data require further investigation in scientific studies and human trials to evaluate the prevention of lifestyle diseases using black soybean polyphenols.
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Affiliation(s)
- Yoko Yamashita
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan.
| | | | - Toshiya Toda
- Department of Innovative Food Sciences, School of Food Sciences and Nutrition, Mukogawa Women's University, Nishinomiya 663-8558, Japan
| | - Hitoshi Ashida
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan.
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Kim YK, Song J. Potential of Glucagon-Like Peptide 1 as a Regulator of Impaired Cholesterol Metabolism in the Brain. Adv Nutr 2020; 11:1686-1695. [PMID: 32627818 PMCID: PMC7666911 DOI: 10.1093/advances/nmaa080] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 06/04/2020] [Accepted: 06/11/2020] [Indexed: 12/25/2022] Open
Abstract
Cerebral vascular diseases are the most common high-mortality diseases worldwide. Their onset and development are associated with glycemic imbalance, genetic background, alteration of atherosclerotic factors, severe inflammation, and abnormal cholesterol metabolism. Recently, the gut-brain axis has been highlighted as the key to the solution for cerebral vessel dysfunction in view of cholesterol metabolism and systemic lipid circulation. In particular, glucagon-like peptide 1 (GLP-1) is a cardinal hormone that regulates blood vessel function and cholesterol homeostasis and acts as a critical messenger between the brain and gut. GLP-1 plays a systemic regulatory role in cholesterol homeostasis and blood vessel function in various organs through blood vessels. Even though GLP-1 has potential in the treatment and prevention of cerebral vascular diseases, the importance of and relation between GLP-1 and cerebral vascular diseases are not fully understood. Herein, we review recent findings on the functions of GLP-1 in cerebral blood vessels in association with cholesterol metabolism.
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Affiliation(s)
- Young-Kook Kim
- Department of Biochemistry, Chonnam National University Medical School, Hwasun, Jeollanam-do, Republic of Korea
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12
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Domae C, Nanba F, Maruo T, Suzuki T, Ashida H, Yamashita Y. Black soybean seed coat polyphenols promote nitric oxide production in the aorta through glucagon-like peptide-1 secretion from the intestinal cells. Food Funct 2019; 10:7875-7882. [PMID: 31746899 DOI: 10.1039/c9fo02050k] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2023]
Abstract
Black soybean seed coat polyphenols were reported to possess various bioregulatory functions. However, the effects of black soybean seed coat polyphenols on vascular functions are unknown. Vascular dysfunction caused by aging and vascular stiffness is associated with a risk of cardiovascular disease (CVD), and a reduction in nitric oxide (NO) levels can trigger the onset of CVD. In the present study, we investigated the effect of polyphenol-rich black soybean seed coat extract (BE) on vascular functions and the underlying mechanisms involved. The oral administration of BE at 50 mg per kg body weight to Wistar rats increased NO levels as determined by eNOS phosphorylation. The administration of BE also increased GLP-1 and cAMP levels. Furthermore, the effects of BE were inhibited in the presence of a GLP-1 receptor antagonist. This suggests that GLP-1 is strongly involved in the underlying mechanism of NO production in vivo. In conclusion, BE contributes to the improvement of vascular functions by promoting NO production. Regarding the putative underlying mechanism, GLP-1 secreted from intestinal cells by the polyphenols in BE activates eNOS in vascular endothelial cells.
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Affiliation(s)
- Chiaki Domae
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Nada-ku, Kobe, Hyogo 657-8501, Japan.
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Sposito AC, Berwanger O, de Carvalho LSF, Saraiva JFK. GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data. Cardiovasc Diabetol 2018; 17:157. [PMID: 30545359 PMCID: PMC6292070 DOI: 10.1186/s12933-018-0800-2] [Citation(s) in RCA: 104] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 12/07/2018] [Indexed: 02/06/2023] Open
Abstract
Patients with type 2 diabetes (T2DM) have a substantial risk of developing cardiovascular disease. The strong connection between the severity of hyperglycaemia, metabolic changes secondary to T2DM and vascular damage increases the risk of macrovascular complications. There is a challenging demand for the development of drugs that control hyperglycaemia and influence other metabolic risk factors to improve cardiovascular outcomes such as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina and heart failure (major adverse cardiovascular events). In recent years, introduction of the new drug class of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has changed the treatment landscape as GLP-1RAs have become well-established therapies in T2DM. The benefits of GLP-1RAs are derived from their pleiotropic effects, which include appetite control, glucose-dependent secretion of insulin and inhibition of glucagon secretion. Importantly, their beneficial effects extend to the cardiovascular system. Large clinical trials have evaluated the cardiovascular effects of GLP-1RAs in patients with T2DM and elevated risk of cardiovascular disease and the results are very promising. However, important aspects still require elucidation, such as the specific mechanisms involved in the cardioprotective effects of these drugs. Careful interpretation is necessary because of the heterogeneity across the trials concerning the definition of cardiovascular risk or cardiovascular disease, baseline characteristics, routine care and event rates. The aim of this review is to describe the main clinical aspects of the GLP-1RAs, compare them using data from both the mechanistic and randomized controlled trials and discuss potential reasons for improved cardiovascular outcomes observed in these trials. This review may help clinicians to decide which treatment is most appropriate in reducing cardiovascular risk in patients with T2DM.
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Affiliation(s)
- Andrei C Sposito
- Atherosclerosis and Vascular Biology Laboratory (AtheroLab), Cardiology Division, Faculty of Medical Sciences, State University of Campinas (Unicamp), 13084-971, Campinas, Sao Paulo, Brazil.
| | - Otávio Berwanger
- Academic Research Organization (ARO), Albert Einstein Hospital, Av. Albert Einstein 627, Sao Paulo, SP, 05651-901, Brazil
| | - Luiz Sérgio F de Carvalho
- Atherosclerosis and Vascular Biology Laboratory (AtheroLab), Cardiology Division, Faculty of Medical Sciences, State University of Campinas (Unicamp), 13084-971, Campinas, Sao Paulo, Brazil
| | - José Francisco Kerr Saraiva
- Cardiology Division, Pontifical Catholic University of Campinas Medicine School, Rua Engenheiro Carlos Stevenson 560, Campinas, Sao Paulo, 13092-132, Brazil
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Simeone P, Liani R, Tripaldi R, Di Castelnuovo A, Guagnano MT, Tartaro A, Bonadonna RC, Federico V, Cipollone F, Consoli A, Santilli F. Thromboxane-Dependent Platelet Activation in Obese Subjects with Prediabetes or Early Type 2 Diabetes: Effects of Liraglutide- or Lifestyle Changes-Induced Weight Loss. Nutrients 2018; 10:nu10121872. [PMID: 30513818 PMCID: PMC6315606 DOI: 10.3390/nu10121872] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 11/20/2018] [Accepted: 11/26/2018] [Indexed: 12/17/2022] Open
Abstract
Thromboxane (TX)-dependent platelet activation and lipid peroxidation, as reflected in vivo by the urinary excretion of 11-dehydro-TXB2 and 8-iso-prostaglandin (PG)F2α, play a key role in atherothrombosis in obesity and type 2 diabetes mellitus (T2DM) since the earlier stages. Thirty-five metformin-treated obese subjects with prediabetes or newly-diagnosed T2DM were randomized to the glucagon-like peptide receptor agonist (GLP-RA) liraglutide (1.8 mg/day) or lifestyle counseling until achieving a comparable weight loss (−7% of initial body weight), to assess whether changes in subcutaneous (SAT) and visceral (VAT) adipose tissue distribution (MRI), insulin sensitivity (Matsuda Index) and beta-cell performance (multiple sampling OGTT beta-index), with either intervention, might affect TX-dependent platelet activation, lipid peroxidation and inflammation. At baseline, Ln-8-iso-PGF2α (Beta = 0.31, p = 0.0088), glycosylated hemoglobin (HbA1c) (Beta = 2.64, p = 0.0011) Ln-TNF-α (Beta = 0.58, p = 0.0075) and SAT (Beta = 0.14, p = 0.044) were significant independent predictors of 11-dehydro-TXB2. After achievement of the weight loss target, a comparable reduction in U-11-dehydro-TXB2 (between-group p = 0.679) and 8-iso-PGF-2α (p = 0.985) was observed in both arms in parallel with a comparable improvement in glycemic control, insulin sensitivity, SAT, high-sensitivity C-reactive protein (hs-CRP). In obese patients with initial impairment of glucose metabolism, the extent of platelet activation is related to systemic inflammation, isoprostane formation and degree of glycemic control and abdominal SAT. Successful weight loss, achieved with either lifestyle changes or an incretin-based therapy, is associated with a significant reduction in lipid peroxidation and platelet activation.
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Affiliation(s)
- Paola Simeone
- Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy.
| | - Rossella Liani
- Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy.
| | - Romina Tripaldi
- Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy.
| | - Augusto Di Castelnuovo
- Department of Epidemiology and Prevention, IRCCS NEUROMED, Via dell'Elettronica, 86077 Pozzilli, Italy.
| | - Maria Teresa Guagnano
- Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy.
| | - Armando Tartaro
- Department of Neuroscience & Imaging, University of Chieti, 66100 Chieti, Italy.
| | - Riccardo C Bonadonna
- Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
- Division of Endocrinology and Metabolic Diseases, Azienda Ospedaliera Universitaria of Parma, 43126 Parma, Italy.
| | | | - Francesco Cipollone
- Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy.
| | - Agostino Consoli
- Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy.
| | - Francesca Santilli
- Department of Medicine and Aging and Center of Aging Science and Translational Medicine (CESI-Met), University of Chieti, 66100 Chieti, Italy.
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15
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Aroor AR, Manrique-Acevedo C, DeMarco VG. The role of dipeptidylpeptidase-4 inhibitors in management of cardiovascular disease in diabetes; focus on linagliptin. Cardiovasc Diabetol 2018; 17:59. [PMID: 29669555 PMCID: PMC5907287 DOI: 10.1186/s12933-018-0704-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Accepted: 04/12/2018] [Indexed: 12/15/2022] Open
Abstract
Multiple population based analyses have demonstrated a high incidence of cardiovascular disease (CVD) and cardiovascular (CV) mortality in subjects with T2DM that reduces life expectancy by as much as 15 years. Importantly, the CV system is particularly sensitive to the metabolic and immune derangements present in obese pre-diabetic and diabetic individuals; consequently, CV dysfunction is often the initial CV derangement to occur and promotes the progression to end organ/tissue damage in T2DM. Specifically, diabetic CVD can manifest as microvascular complications, such as nephropathy, retinopathy, and neuropathy, as well as, macrovascular impairments, including ischemic heart disease, peripheral vascular disease, and cerebrovascular disease. Despite some progress in prevention and treatment of CVD, mainly via blood pressure and dyslipidemia control strategies, the impact of metabolic disease on CV outcomes is still a major challenge and persists in proportion to the epidemics of obesity and diabetes. There is abundant pre-clinical and clinical evidence implicating the DPP-4-incretin axis in CVD. In this regard, linagliptin is a unique DPP-4 inhibitor with both CV and renal safety profiles. Moreover, it exerts beneficial CV effects beyond glycemic control and beyond class effects. Linagliptin is protective for both macrovascular and microvascular complications of diabetes in preclinical models, as well as clinical models. Given the role of endothelial-immune cell interactions as one of the key events in the initiation and progression of CVD, linagliptin modulates these cell–cell interactions by affecting two important pathways involving stimulation of NO signaling and potent inhibition of a key immunoregulatory molecule.
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Affiliation(s)
- Annayya R Aroor
- Diabetes and Cardiovascular Center, University of Missouri School of Medicine, Columbia, MO, USA.,Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri-Columbia School of Medicine, One Hospital Drive, Columbia, MO, 65212, USA.,Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA
| | - Camila Manrique-Acevedo
- Diabetes and Cardiovascular Center, University of Missouri School of Medicine, Columbia, MO, USA.,Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri-Columbia School of Medicine, One Hospital Drive, Columbia, MO, 65212, USA.,Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA
| | - Vincent G DeMarco
- Diabetes and Cardiovascular Center, University of Missouri School of Medicine, Columbia, MO, USA. .,Division of Endocrinology and Metabolism, Department of Medicine, University of Missouri-Columbia School of Medicine, One Hospital Drive, Columbia, MO, 65212, USA. .,Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA. .,Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA.
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