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Lee H, Fernandes M, Lee J, Merino J, Kwak SH. Exploring the shared genetic landscape of diabetes and cardiovascular disease: findings and future implications. Diabetologia 2025; 68:1087-1100. [PMID: 40088285 PMCID: PMC12069157 DOI: 10.1007/s00125-025-06403-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 01/28/2025] [Indexed: 03/17/2025]
Abstract
Diabetes is a rapidly growing global health concern projected to affect one in eight adults by 2045, which translates to roughly 783 million people. The profound metabolic alterations often present in dysglycaemia significantly increase the risk of cardiovascular complications. While genetic susceptibility plays a crucial role in diabetes and its vascular complications, identifying genes and molecular mechanisms that influence both diseases simultaneously has proven challenging. A key reason for this challenge is the pathophysiological heterogeneity underlying these diseases, with multiple processes contributing to different forms of diabetes and specific cardiovascular complications. This molecular heterogeneity has limited the effectiveness of large-scale genome-wide association studies (GWAS) in identifying shared underlying mechanisms. Additionally, our limited knowledge of the causal genes, cell types and disease-relevant states through which GWAS signals operate has hindered the discovery of common molecular pathways. This review highlights recent advances in genetic epidemiology, including studies of causal associations that have uncovered genetic and molecular factors influencing both dysglycaemia and cardiovascular complications. We explore how disease subtyping approaches can be critical in pinpointing the unique molecular signatures underlying both diabetes and cardiovascular complications. Finally, we address critical research gaps and future opportunities to advance our understanding of both diseases and translate these discoveries into tangible benefits for patient care and population health.
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Affiliation(s)
- Hyunsuk Lee
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Korea
- Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea
- Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
| | - Maria Fernandes
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Jeongeun Lee
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Korea
| | - Jordi Merino
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
- Diabetes Unit, Endocrine Division, Massachusetts General Hospital, Boston, MA, USA.
- Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
| | - Soo Heon Kwak
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Korea.
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2
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Phan JP, Kinninger A, Roy SK, Bhandari M, Budoff MJ. The effect of diabetes on plaque, stenosis, and coronary artery calcium score. J Cardiovasc Comput Tomogr 2025:S1934-5925(25)00086-3. [PMID: 40340101 DOI: 10.1016/j.jcct.2025.04.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2025] [Revised: 04/27/2025] [Accepted: 04/28/2025] [Indexed: 05/10/2025]
Affiliation(s)
- Jonathan P Phan
- Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
| | | | - Sion K Roy
- Lundquist Institute, Torrance, CA, USA; Division of Cardiology, Harbor-UCLA Medical Center, Torrance, CA, USA.
| | | | - Matthew J Budoff
- Lundquist Institute, Torrance, CA, USA; Division of Cardiology, Harbor-UCLA Medical Center, Torrance, CA, USA.
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Lee SN, Malhotra P, Miller RJH, Gransar H, Hayes SW, Friedman JD, Thomson LEJ, Rozanski A, Slomka PJ, Han D, Berman DS. Independent prognostic significance of myocardial flow reserve over coronary artery calcium, myocardial perfusion, and clinical variables in patients without known coronary artery disease, according to diabetes status. J Nucl Cardiol 2025; 47:102165. [PMID: 39983863 DOI: 10.1016/j.nuclcard.2025.102165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 12/17/2024] [Accepted: 02/04/2025] [Indexed: 02/23/2025]
Abstract
OBJECTIVE To explore differences in prevalence and prognosis associated with reduced myocardial flow reserve (MFR) in patients without known coronary artery disease (CAD) based on diabetes status. METHODS Of 2639 patients without known CAD who underwent rubidium positron emission tomography myocardial perfusion imaging (MPI), 818 patients (31%) had diabetes. Reduced MFR was defined as MFR <2.0. Coronary artery calcium (CAC) score was categorized as 0, 1-99, 100-399, and ≥400. Ischemic total perfusion deficit (TPD) was categorized as <1%, 1-<5%, and ≥5%. Outcome variables were all-cause death (ACD) and non-fatal myocardial infarction (MI). RESULTS During the median follow-up of 4.1 years, 574 (21.8%) ACD/MI occurred (204 [25.1%] diabetic patients, 370 [20.3%] nondiabetic patients). In multivariable Cox analysis, reduced MFR was associated with increased ACD/MI in patients with diabetes (per .1 decrease: HR: 1.04, 95% CI: 1.02-1.06, P < .001) and patients without diabetes (per .1 decrease: HR: 1.03, 95% CI: 1.02-1.04, P < .001). No interaction existed between diabetes and MFR for ACD/MI risk regardless of CAC or ischemic burden (all P > .05). Adding MFR to the risk prediction model of clinical, conventional MPI findings, and CAC improved the discrimination for clinical outcomes in both groups (DM: .003, non-DM: <.001, respectively). CONCLUSION Reduced MFR was more common in patients with diabetes and an important independent prognostic marker over CAC and clinical variables. The association between MFR and ACD/MI risk did not differ between patients with and without diabetes who had no prior CAD, regardless of CAC and ischemic burden.
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Affiliation(s)
- Su Nam Lee
- Mark Taper Imaging Center, Cedars Sinai Medical Center, Los Angeles, CA, USA; Division of Cardiology, Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Seoul, Republic of Korea
| | - Pankaj Malhotra
- Mark Taper Imaging Center, Cedars Sinai Medical Center, Los Angeles, CA, USA; Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Robert J H Miller
- Department of Cardiac Sciences, University of Calgary, 24 Ave NW, Calgary, AB, Canada
| | - Heidi Gransar
- Mark Taper Imaging Center, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Sean W Hayes
- Mark Taper Imaging Center, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - John D Friedman
- Mark Taper Imaging Center, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Louise E J Thomson
- Mark Taper Imaging Center, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Alan Rozanski
- Division of Cardiology, Mount Sinai St. Luke's Hospital, New York, NY, USA
| | - Piotr J Slomka
- Biomedical Imaging Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Donghee Han
- Mark Taper Imaging Center, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Daniel S Berman
- Mark Taper Imaging Center, Cedars Sinai Medical Center, Los Angeles, CA, USA; Division of Cardiology, Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
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Serra M, Mollace R, Ritorto G, Ussia S, Altomare C, Tavernese A, Preianò M, Palma E, Muscoli C, Mollace V, Macrì R. A Systematic Review of Thiamine Supplementation in Improving Diabetes and Its Related Cardiovascular Dysfunction. Int J Mol Sci 2025; 26:3932. [PMID: 40362174 PMCID: PMC12072100 DOI: 10.3390/ijms26093932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Revised: 04/16/2025] [Accepted: 04/20/2025] [Indexed: 05/15/2025] Open
Abstract
The significance of thiamine in human health is linked to its role in several pathways that control different disease processes. Significant improvements in cardiometabolic diseases, substantially impacted by thiamine imbalances, are observed with thiamine supplementation. Diabetic patients could see a reduction in cardiovascular (CV) risk due to thiamine's significant impact on glucose metabolism. Specifically, increased ventricular filling pressures and oxygen consumption, indicative of CV dysfunction, are caused by oxidative and inflammatory damage to blood vessels, diabetic nephropathy, and elevated lactic acid production. Despite promising pre-clinical results for thiamine, clinical trials have yielded conflicting and contradictory findings due to limitations like small sample sizes and insufficient follow-up. To provide a summary of clinical study results, this systematic review assessed the impact of thiamine supplementation on diabetes and its CV complications. The studies included in this systematic review were retrieved from PubMed and Medline databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and following the Population Intervention Comparison Outcome (PICO) framework. Seven clinical studies were identified, which enlighten the association between thiamine supplementation, hyperglycemia, and cardiovascular disease (CVD). Although large-scale, multicenter studies with longer follow-up periods are needed, the association between thiamine and chronic metabolic dysfunction related to CV risk suggests its crucial role in preventing severe heart failure (HF).
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Affiliation(s)
- Maria Serra
- Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (M.S.); (G.R.); (S.U.); (C.A.); (C.M.); (V.M.)
| | - Rocco Mollace
- Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (M.S.); (G.R.); (S.U.); (C.A.); (C.M.); (V.M.)
- Department of Experimental Medicine, University “Tor Vergata” of Rome, 00133 Rome, Italy
| | - Giovanna Ritorto
- Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (M.S.); (G.R.); (S.U.); (C.A.); (C.M.); (V.M.)
| | - Sara Ussia
- Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (M.S.); (G.R.); (S.U.); (C.A.); (C.M.); (V.M.)
| | - Carmen Altomare
- Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (M.S.); (G.R.); (S.U.); (C.A.); (C.M.); (V.M.)
| | - Annamaria Tavernese
- Department of Medicine and Surgery, University Campus Bio-Medico of Rome, 00128 Rome, Italy;
| | - Mariaimmacolata Preianò
- Laboratory of Mass Spectrometry and Proteomics, Department of Health Sciences, “Magna Græcia” University, 88100 Catanzaro, Italy;
| | - Ernesto Palma
- Veterinary Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy;
| | - Carolina Muscoli
- Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (M.S.); (G.R.); (S.U.); (C.A.); (C.M.); (V.M.)
| | - Vincenzo Mollace
- Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (M.S.); (G.R.); (S.U.); (C.A.); (C.M.); (V.M.)
- Renato Dulbecco Institute, 88046 Lamezia Terme, Italy
| | - Roberta Macrì
- Pharmacology Laboratory, Institute of Research for Food Safety and Health IRC-FSH, Department of Health Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (M.S.); (G.R.); (S.U.); (C.A.); (C.M.); (V.M.)
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Ibarra-Lara L, Sánchez-López A, del Valle-Mondragon L, Soria-Castro E, Zarco-Olvera G, Patlán M, Guarner-Lans V, Torres-Narváez JC, Ruiz-Ramírez A, Díaz de León-Sánchez F, Oidor-Chan VH, Castrejón-Téllez V. Involvement of Nuclear Receptors PPAR-α, PPAR-γ, and the Transcription Factor Nrf2 in Cellular Protection Against Oxidative Stress Regulated by H 2S and Induced by Hypoxia-Reoxygenation and High Glucose in Primary Cardiomyocyte Cultures. Antioxidants (Basel) 2025; 14:482. [PMID: 40298815 PMCID: PMC12024258 DOI: 10.3390/antiox14040482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 04/11/2025] [Accepted: 04/12/2025] [Indexed: 04/30/2025] Open
Abstract
Myocardial oxidative stress increases under conditions of hyperglycemia and ischemia/reperfusion (I/R) injury, leading to cellular damage. Inhibition of oxidative stress is involved in the cardioprotective effects of hydrogen sulfide (H2S) during I/R and diabetes, and H2S has the potential to protect the heart. However, the mechanism by which H2S regulates the level of cardiac reactive oxygen species (ROS) during I/R and hyperglycemic conditions remains unclear. Therefore, the objective of this study was to evaluate the cytoprotective effect of H2S in primary cardiomyocyte cultures subjected to hyperglycemia, hypoxia-reoxygenation (HR), or both conditions, by assessing the PPAR-α/Keap1/Nrf2/p47phox/NOX4/p-eNOS/CAT/SOD and the PPAR-γ/PGC-1α/AMPK/GLUT4 signaling pathways. Treatment with NaHS (100 μM) as an H2S donor in cardiomyocytes subjected to hyperglycemia, HR, or a combination of both increased cell viability, total antioxidant capacity, and tetrahydrobiopterin (BH4) concentrations, while reducing ROS production, malondialdehyde concentrations, 8-hydroxy-2'-deoxyguanosine, and dihydrobiopterin (BH2) concentrations. Additionally, the H2S donor treatment increased the expression and activity of PPAR-α, reversed the reduction in the expression of PPAR-γ, PGC-1α, AMPK, GLUT4, Nrf2, p-eNOS, SOD, and CAT, and decreased the expression of Keap1, p47phox and NOX4. Therefore, the treatment with the H2S donor protects cardiomyocytes from damage caused by hyperglycemia, HR, or both conditions by reducing oxidative stress markers and improving antioxidant mechanisms, thereby increasing cell viability and "cardiomyocyte ultrastructure".
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Affiliation(s)
- Luz Ibarra-Lara
- Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico; (L.I.-L.); (L.d.V.-M.); (G.Z.-O.); (J.C.T.-N.)
| | - Araceli Sánchez-López
- Department of Pharmacobiology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City 07360, Mexico;
| | - Leonardo del Valle-Mondragon
- Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico; (L.I.-L.); (L.d.V.-M.); (G.Z.-O.); (J.C.T.-N.)
| | - Elizabeth Soria-Castro
- Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Chavez, Mexico City 14080, Mexico; (E.S.-C.); (A.R.-R.)
| | - Gabriela Zarco-Olvera
- Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico; (L.I.-L.); (L.d.V.-M.); (G.Z.-O.); (J.C.T.-N.)
| | - Mariana Patlán
- Subdirectorate of Basic and Technological Research, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico;
| | - Verónica Guarner-Lans
- Department of Physiology, National Institute of Cardiology Ignacio Chavez, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico;
| | - Juan Carlos Torres-Narváez
- Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Mexico City 14080, Mexico; (L.I.-L.); (L.d.V.-M.); (G.Z.-O.); (J.C.T.-N.)
| | - Angélica Ruiz-Ramírez
- Department of Cardiovascular Biomedicine, National Institute of Cardiology Ignacio Chavez, Mexico City 14080, Mexico; (E.S.-C.); (A.R.-R.)
| | - Fernando Díaz de León-Sánchez
- Laboratory of Post-harvest of Plant Genetic Resources and Natural Products, Department of Health Sciences, Autonomous Metropolitan University, Iztapalapa Campus, Mexico City 09310, Mexico;
| | - Víctor Hugo Oidor-Chan
- Department of Biotechnology, Autonomous Metropolitan University, Iztapalapa Campus, Av. Ferrocarril San Rafael Atlixco 186, Leyes de Reforma, Iztapalapa, Mexico City 09310, Mexico
| | - Vicente Castrejón-Téllez
- Department of Physiology, National Institute of Cardiology Ignacio Chavez, Juan Badiano 1, Sección XVI, Tlalpan, Mexico City 14080, Mexico;
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Berger M, Marx N, Marx-Schütt K. Cardiovascular Risk Reduction in Patients with Type 2 Diabetes: What Does the Cardiologist Need to Know? Eur Cardiol 2025; 20:e09. [PMID: 40309220 PMCID: PMC12042294 DOI: 10.15420/ecr.2024.29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 11/29/2024] [Indexed: 05/02/2025] Open
Abstract
Patients with diabetes are at an increased risk of cardiovascular disease (CVD), including atherosclerotic CVD and heart failure. In addition, diabetes is associated with a higher risk of developing chronic kidney disease, which is considered to be one of the strongest risk factors for CVD and mortality. To address the increased cardiovascular risk of patients with diabetes, dedicated screening strategies for CVD are necessary; conversely, screening for diabetes needs to be performed in all patients with CVD to allow timely identification. Once diabetes is diagnosed, rapid implementation of treatment with therapies to reduce cardiovascular risk on top of standard of care is necessary. This review gives an overview of contemporary therapeutic strategies to reduce cardiovascular risk in patients with type 2 diabetes.
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Affiliation(s)
- Martin Berger
- Department of Internal Medicine I, University Hospital Aachen Aachen, Germany
| | - Nikolaus Marx
- Department of Internal Medicine I, University Hospital Aachen Aachen, Germany
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Qu B, Li Z, Hu W. Exploration of metformin-based drug combination for mitigating diabetes-associated atherosclerotic diseases. World J Diabetes 2025; 16:100533. [PMID: 40236872 PMCID: PMC11947926 DOI: 10.4239/wjd.v16.i4.100533] [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: 08/20/2024] [Revised: 12/30/2024] [Accepted: 01/10/2025] [Indexed: 02/28/2025] Open
Abstract
Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications. The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism, thus contributing to the development of vascular disorders, especially atherosclerotic diseases. Aggressive glycemic control combined with vascular intervention is critical to the prevention and treatment of diabetes-associated atherosclerosis. It is suggested that metformin should be combined with hypoglycemic agents with proven vascular benefits for treating type 2 diabetes (T2DM) complicated with atherosclerotic diseases. Clinical studies indicates that the preferred combination is metformin with either glucagon-like peptide-1 receptor agonist or sodium/glucose cotransporter-2 inhibitor, which could offer additional vascular benefits and reduce the risk of atherosclerotic complications. Likewise, combination therapy with metformin and hypolipidemic agents has also shown additive effects on glucose control and lipid-lowering in patients with both diabetes and dyslipidemia, whereas extensive clinical trials using atherosclerotic-associated outcomes are required to support the vascular benefits. Moreover, co-administration of metformin with systemic antioxidant or anti-inflammatory therapy may also provide additional vascular benefits as indicated by several animal studies. For instance, a recent study found that additional supplementation of cholecalciferol and taurine enhanced metformin efficacy in controlling diabetes while reducing the risk of associated atherosclerotic complications. However, these potential benefits remain need validation by the evidence from clinical studies. Despite the limitations, such as heterogeneity across different patient populations, and deficiency in long-term outcomes, such efforts can contribute to finding optimal drug combinations to improve the management of T2DM and reduce its atherosclerotic complications.
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Affiliation(s)
- Biao Qu
- Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Zheng Li
- Jiangsu Engineering Research Center of Cardiovascular Drugs Targeting Endothelial Cells, College of Health Sciences, School of Life Sciences, Jiangsu Normal University, Xuzhou 221000, Jiangsu Province, China
| | - Wei Hu
- Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
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Fernandes Silva L, Laakso M. Advances in Metabolomics: A Comprehensive Review of Type 2 Diabetes and Cardiovascular Disease Interactions. Int J Mol Sci 2025; 26:3572. [PMID: 40332079 PMCID: PMC12027308 DOI: 10.3390/ijms26083572] [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: 03/09/2025] [Revised: 04/03/2025] [Accepted: 04/05/2025] [Indexed: 05/08/2025] Open
Abstract
Type 2 diabetes (T2D) and cardiovascular diseases (CVDs) are major public health challenges worldwide. Metabolomics, the exhaustive assessment of metabolites in biological systems, offers important insights regarding the metabolic disturbances related to these disorders. Recent advances toward the integration of metabolomics into clinical practice to facilitate the discovery of novel biomarkers that can improve the diagnosis, prognosis, and treatment of T2D and CVDs are discussed in this review. Metabolomics offers the potential to characterize the key metabolic alterations associated with disease pathophysiology and treatment. T2D is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms; therefore, the disease-causing pathways of T2D are not completely understood. Recent studies have identified several robust clusters of T2D variants representing biologically meaningful, distinct pathways, such as the beta cell and proinsulin cluster related to pancreatic insulin secretion, obesity, lipodystrophy, the liver/lipid cluster, glycemia, and blood pressure, and metabolic syndrome clusters representing different pathways causing insulin resistance. Regarding CVDs, recent studies have allowed the metabolomic profile to delineate pathways that contribute to atherosclerosis and heart failure, as well as to the development of targeted therapy. This review also covers the role of metabolomics in integrated metabolic genomics and other omics platforms to better understand disease mechanisms, along with the transition toward precision medicine. This review further investigates the use of metabolomics in multi-metabolite modeling to enhance risk prediction models for predicting the first occurrence of major adverse cardiovascular events among individuals with T2D, highlighting the value of such approaches in optimizing the preventive and therapeutic models used in clinical practice.
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Affiliation(s)
- Lilian Fernandes Silva
- Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland;
- Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
| | - Markku Laakso
- Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, 70210 Kuopio, Finland;
- Department of Medicine, Kuopio University Hospital, 70200 Kuopio, Finland
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Ding Y, Shan D, Han T, Liu Z, Wang X, Dou G, Xin R, Guo Z, Chen G, Jing J, He B, Chen Y, Yang J. Incremental Prognostic Value of Perivascular Fat Attenuation Index in Patients with Diabetes with Coronary Artery Disease. Radiol Cardiothorac Imaging 2025; 7:e240242. [PMID: 40042997 DOI: 10.1148/ryct.240242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2025]
Abstract
Purpose To investigate whether pericoronary adipose tissue attenuation (PCATa) provides incremental prognostic value over commonly used coronary CT angiography (CCTA) parameters for predicting major adverse cardiovascular and cerebrovascular events (MACCE) in individuals with diabetes mellitus (DM). Materials and Methods This prospective study included consecutive patients with type 2 DM who underwent CCTA due to suspected coronary artery disease between January 2015 and December 2017. PCATa of three coronary arteries was measured and evaluated. Cox proportional hazards regression was performed to investigate the prognostic value of PCATa for predicting MACCE. The incremental prognostic value of PCATa for MACCE was evaluated by comparing area under the receiver operating characteristic curve (AUC) values of four models (model 1: clinical characteristics, model 2: model 1 + conventional CCTA findings [coronary artery calcium score, Leiden score], model 3: model 2 + advanced CCTA findings [high-risk plaque, CT fractional flow reserve], model 4: model 3 + PCATa). Results Of the 1029 participants (mean age, 60.2 years ± 9.9 [SD]; 539 male) included in the study, 152 (14.8%) experienced MACCE during a median follow-up of 56.5 months. PCATa independently predicted MACCE after adjustment for clinical characteristics and commonly used CCTA findings (hazard ratio, 1.86 [95% CI: 1.24, 2.80]; P = .003). The model incorporating PCATa improved predictive performance for MACCE compared with the model including clinical characteristics and conventional and advanced CCTA parameters (AUC, 0.75 [95% CI: 0.71, 0.79] vs 0.73 [95% CI: 0.68, 0.77]; P = .009). Conclusion PCATa provided incremental prognostic value beyond clinical characteristics and other CCTA findings for prediction of MACCE in individuals with DM. Keywords: CT Angiography, Cardiac, Coronary Arteries, Inflammation, Outcomes Analysis, Coronary Computed Tomography Angiography, Diabetes Mellitus, Coronary Inflammation, Pericoronary Adipose Tissue Attenuation Supplemental material is available for this article. © RSNA, 2025.
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Affiliation(s)
- Yipu Ding
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
- School of Medicine, Nankai University, Tianjin, China
| | - Dongkai Shan
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
| | - Tianwen Han
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
| | - Zinuan Liu
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
- Medical School of Chinese PLA, Beijing, China
| | - Xi Wang
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
- Department of Cardiology, the First Medical Center of PLA General Hospital, Beijing, China
| | - Guanhua Dou
- Department of Cardiology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Ran Xin
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
- School of Medicine, Nankai University, Tianjin, China
| | - Ziqiang Guo
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
- Medical School of Chinese PLA, Beijing, China
| | - Guanxi Chen
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
- Medical School of Chinese PLA, Beijing, China
| | - Jing Jing
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
- Department of Cardiology, the First Medical Center of PLA General Hospital, Beijing, China
| | - Bai He
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
- Department of Cardiology, the First Medical Center of PLA General Hospital, Beijing, China
| | - Yundai Chen
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
- Department of Cardiology, the First Medical Center of PLA General Hospital, Beijing, China
| | - Junjie Yang
- Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, No. 6 Fucheng Road, Haidian District, Beijing 100048, China
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Son H, Sohn SH, Kim HA, Choe HJ, Lee H, Jung HS, Cho YM, Park KS, Hwang HY, Kwak SH. Real-time continuous glucose monitoring improves postoperative glucose control in people with type 2 diabetes mellitus undergoing coronary artery bypass grafting: A randomized clinical trial. Diabetes Obes Metab 2025; 27:1836-1844. [PMID: 39776241 DOI: 10.1111/dom.16177] [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: 09/26/2024] [Revised: 12/18/2024] [Accepted: 12/26/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND Effective glycaemic control following cardiac surgery improves clinical outcomes, and continuous glucose monitoring (CGM) might be a valuable tool in achieving this objective. We investigated the effect of real-time CGM and telemonitoring on postoperative glycaemic control in people with type 2 diabetes (T2D) after coronary artery bypass grafting (CABG). METHODS In this randomized clinical trial (RCT), adults with T2D undergoing CABG were assigned to either a test group utilizing real-time CGM (Dexcom G6) and telemetry for glycaemic control, or a control group with blinded CGM measures, relying on point-of-care measures. The primary outcome was the percentage of time in range (TIR) of blood glucose between 70 and 180 mg/dL (3.9-10.0 mmol/L), measured by CGM. RESULTS Among 91 subjects, 48 were in the test group and 43 were in the control group. The least squares (LS) mean ± standard error of TIR was 60.3 ± 2.7%, 50.3 ± 2.9% in the test and control group, respectively. The test group had significantly higher TIR when adjusted with age, sex, body mass index, baseline fasting blood glucose and baseline glycated haemoglobin (LS mean difference, 10.0%; 95% confidence interval, 2.1-18.0; p = 0.014). The test group also had lower time above range and mean glucose levels, with no differences in time below range or hypoglycaemic events. CONCLUSIONS In this RCT, real-time CGM and telemonitoring improved glycaemic control during postoperative period without increasing hypoglycaemia risk. Given the benefits of effective glycaemic control on perioperative outcomes, CGM may be helpful in managing T2D after CABG.
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Affiliation(s)
- Heejun Son
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Suk Ho Sohn
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Ah Kim
- Division of Endocrinology, Department of Internal Medicine, Veteran Health Service Medical Center, Seoul, Korea
| | - Hun Jee Choe
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Hyunsuk Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea
- Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
| | - Hye Seung Jung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Young Min Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Divison of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Kyong Soo Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Divison of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Ho Young Hwang
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Soo Heon Kwak
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Divison of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Innovative Medical Technology Research Institute, Seoul National University Hospital, Seoul, Korea
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Michikura M, Ogura M, Hori M, Matsuki K, Makino H, Fujioka S, Shishikura D, Hoshiga M, Harada-Shiba M. Association of Achilles tendon thickness with lipid profile and carotid IMT in patients with familial hypercholesterolemia. Atherosclerosis 2025; 403:119173. [PMID: 40158303 DOI: 10.1016/j.atherosclerosis.2025.119173] [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: 12/08/2024] [Revised: 02/10/2025] [Accepted: 03/05/2025] [Indexed: 04/02/2025]
Abstract
BACKGROUND AND AIMS Familial hypercholesterolemia (FH) is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and Achilles tendon (AT) thickening. AT thickness (ATT) is useful for diagnosing FH and assessing the risk of coronary artery disease (CAD). Nevertheless, the relationship between AT thickening and lipid profile is not clear. We investigated the association of ATT with lipid Profile and carotid IMT. METHODS We included 450 patients with clinically diagnosed heterozygous FH. ATT was measured by ultrasonography. RESULTS The rate of thickening increased for both AT and carotid-IMT according to age (p < 0.001). In the teens, there was no carotid-IMT thickening, but 39 % of the subjects had a thickened AT. The thresholds of cumulative LDL-C values for AT and carotid-IMT thickening based on ROC curves were 9210 mg/dL∗years (AUC: 0.66, 95 % CI: 0.61-0.72) for ATT and 11,255 mg/dL∗years (AUC: 0.79, 95 % CI: 0.75-0.84) for carotid-IMT. For cumulative LDL-C levels ≥ median, untreated HDL-C level was lower in the AT thickened group than in the non-thickened group (AT thickened: 52 (43-63) mg/dL, non-thickened: 63 (52-72) mg/dL). There was a significant correlation between ATT and cumulative LDL-C (Male: R = 0.48 p < 0.001, Female: R = 0.33 p < 0.001). CONCLUSIONS We clarified that both cumulative exposure to LDL-C and untreated HDL-C levels were closely related to AT thickening. Our results show that in ultrasonographic assessment, ATT is more useful than carotid-IMT for predicting the degree of lipid deposition in tissues, especially in young adults.
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Affiliation(s)
- Masahito Michikura
- Department of Endocrinology and Metabolism, National Cerebral and Cardiovascular Center Hospital, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan; Department of Cardiology, Osaka Medical and Pharmaceutical University, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan.
| | - Masatsune Ogura
- Department of Clinical Laboratory Technology, Faculty of Medical Science, Juntendo University, 6-8-1 Hinode, Urayasu, Chiba, 279-0013, Japan
| | - Mika Hori
- Department of Endocrinology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8601, Japan
| | - Kota Matsuki
- Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho Hirosaki City, Aomori, 036-8562. Japan
| | - Hisashi Makino
- Department of Endocrinology and Metabolism, National Cerebral and Cardiovascular Center Hospital, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan
| | - Shimpei Fujioka
- Department of Cardiology, Osaka Medical and Pharmaceutical University, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan
| | - Daisuke Shishikura
- Department of Cardiology, Osaka Medical and Pharmaceutical University, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan
| | - Masaaki Hoshiga
- Department of Cardiology, Osaka Medical and Pharmaceutical University, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan
| | - Mariko Harada-Shiba
- Cardiovascular Center, Osaka Medical and Pharmaceutical University, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan
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Gupta A, Goyal P, Roy S, Jana P, Chauhan A, Jilowa S, Panghal Y. Soluble receptor for advanced glycation end products and its role in cardiovascular risk assessment in hyperglycemia - A study in North India. J Family Med Prim Care 2025; 14:1325-1332. [PMID: 40396087 PMCID: PMC12088533 DOI: 10.4103/jfmpc.jfmpc_1356_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 10/24/2024] [Accepted: 10/26/2024] [Indexed: 05/22/2025] Open
Abstract
Introduction Advanced glycation end products (AGEs) and their cellular receptors (RAGEs) play an important role in the pathogenesis of type 2 diabetes mellitus and its progression to cardiovascular disease (CVD). A marker of the AGE-RAGE axis, soluble RAGE (sRAGE), was examined in this study in various glycemic states as well as in low- and high-CVD-risk patients. Methods In this cross-sectional study, 25 adults were recruited into each of the "Normoglycemic", "Prediabetic", and "Diabetic" groups based on American Diabetes Association 2019 HbA1c% level criteria. Using online American Heart Association Atherosclerotic CVD (AHA ASCVD) risk calculator and guidelines, patients were classified into "Low" and "High" risk categories. Serum sRAGE was assayed using sandwich ELISA technology. Serum markers necessary for calculation of homeostatic model assessment for insulin resistance (HOMA-IR) and atherogenic index of plasma (AIP) were spectrophotometrically estimated. Carotid intima-media thickness (CIMT) was analyzed using B-mode carotid ultrasonography. Results Mann-Whitney U analysis showed that sRAGE, AIP, HOMA-IR, CIMT, and %10-year CVD risk values were significantly different in the two ASCVD risk categories. Spearman test showed a significant correlation between sRAGE and other markers. ROC curve analysis demonstrated a higher area under the curve for sRAGE than other known parameters to differentiate between ASCVD risk categories. Finally, odds ratio analysis showed that sRAGE had higher odds of detecting high CVD risk than AIP or CIMT. Conclusions Our study has demonstrated the possible role of sRAGE in CVD development and suggests that they may serve as screening markers for future CVD risk.
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Affiliation(s)
- Aparna Gupta
- Department of Biochemistry, Lady Hardinge Medical College and Associated Hospitals, University of Delhi, New Delhi, India
| | - Parul Goyal
- Department of Biochemistry, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, Guru Gobind Singh Indraprastha University, New Delhi, India
| | - Smita Roy
- Department of Biochemistry, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, Guru Gobind Singh Indraprastha University, New Delhi, India
| | - Pratip Jana
- Department of Biochemistry, Lady Hardinge Medical College and Associated Hospitals, University of Delhi, New Delhi, India
| | - Ajay Chauhan
- Department of Medicine, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, Guru Gobind Singh Indraprastha University, New Delhi, India
| | - Sarita Jilowa
- Department of Radiology, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, Guru Gobind Singh Indraprastha University, New Delhi, India
| | - Yashasvi Panghal
- Department of Biochemistry, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, Guru Gobind Singh Indraprastha University, New Delhi, India
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Tashkandi AJ, Gorman A, McGoldrick Mathers E, Carney G, Yacoub A, Setyaningsih WAW, Kuburas R, Margariti A. Metabolic and Mitochondrial Dysregulations in Diabetic Cardiac Complications. Int J Mol Sci 2025; 26:3016. [PMID: 40243689 PMCID: PMC11988959 DOI: 10.3390/ijms26073016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 03/16/2025] [Accepted: 03/24/2025] [Indexed: 04/18/2025] Open
Abstract
The growing prevalence of diabetes highlights the urgent need to study diabetic cardiovascular complications, specifically diabetic cardiomyopathy, which is a diabetes-induced myocardial dysfunction independent of hypertension or coronary artery disease. This review examines the role of mitochondrial dysfunction in promoting diabetic cardiac dysfunction and highlights metabolic mechanisms such as hyperglycaemia-induced oxidative stress. Chronic hyperglycaemia and insulin resistance can activate harmful pathways, including advanced glycation end-products (AGEs), protein kinase C (PKC) and hexosamine signalling, uncontrolled reactive oxygen species (ROS) production and mishandling of Ca2+ transient. These processes lead to cardiomyocyte apoptosis, fibrosis and contractile dysfunction. Moreover, endoplasmic reticulum (ER) stress and dysregulated RNA-binding proteins (RBPs) and extracellular vesicles (EVs) contribute to tissue damage, which drives cardiac function towards heart failure (HF). Advanced patient-derived induced pluripotent stem cell (iPSC) cardiac organoids (iPS-COs) are transformative tools for modelling diabetic cardiomyopathy and capturing human disease's genetic, epigenetic and metabolic hallmarks. iPS-COs may facilitate the precise examination of molecular pathways and therapeutic interventions. Future research directions encourage the integration of advanced models with mechanistic techniques to promote novel therapeutic strategies.
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Affiliation(s)
| | | | | | | | | | | | - Refik Kuburas
- Wellcome Wolfson Institute of Experimental Medicine, Queens University Belfast, Belfast BT9 7BL, Northern Ireland, UK; (A.J.T.); (A.G.); (E.M.M.); (G.C.); (A.Y.); (W.A.W.S.)
| | - Andriana Margariti
- Wellcome Wolfson Institute of Experimental Medicine, Queens University Belfast, Belfast BT9 7BL, Northern Ireland, UK; (A.J.T.); (A.G.); (E.M.M.); (G.C.); (A.Y.); (W.A.W.S.)
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14
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Kucera J, Duggan J, Peters A, Trachiotis G. Transit time flow management as a management strategy in high-risk groups undergoing coronary artery bypass grafting. J Cardiothorac Surg 2025; 20:158. [PMID: 40119360 PMCID: PMC11927366 DOI: 10.1186/s13019-025-03408-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 03/14/2025] [Indexed: 03/24/2025] Open
Abstract
BACKGROUND We evaluated the surgical outcomes in three groups of individuals with diabetes mellitus (DM), end-stage renal disease (ESRD), and on (ONCAB) vs. off-pump (OPCAB) coronary artery bypass grafting (CABG). We also examined the changes in intraoperative decision-making when ultrasound and transit-time flow measurement was utilized in the operating room. This study will aim to identify the utility of HFUS and TTFM in high-risk patient categories. METHODS Data from the multicenter REQUEST (Registry for Quality assessment with ultrasound imaging and TTFM measurement in cardiac bypass surgery) had recently been compiled in three separate papers examining outcomes in patients with DM, ESRD, and on vs. off-pump bypass grafting. Data was extrapolated to determine the impact of HFUS and TTFM in patients with diabetes, ESRD, ONCAB and OPCAB. The primary outcome measured in in the REQUEST study is any change in planned surgical procedure. Secondary end points include rate of changes, coronary targets, completed grafts, and in-hospital morbidity and mortality. RESULTS Outcomes were predicated upon patient population surveyed. The REQUEST registry reported 1016 individuals who underwent CABG. For individuals with DM, any surgical change to the coronary target was slightly lower, measured at a change rate of 11.6% vs. 9.5% (OR 0.80, 95% CI 0.53-1.21, P = 0.288). In diabetics, the aortic component of the operation underwent a higher rate of surgical strategy change with TTFM compared to without (10.2% vs. 6.4%, OR 1.67, 95% CI 1.06-2.65; P = 0.026). In patients with ESRD, TTFM increased the rate of strategy changes compared to no TTFM (33.7% vs. 24.3%, 95% CI 1.01-2.48, P = 0.047) and number of revisions per graft (7.0% vs. 3.4%, OR 2.14, 95% CI 1.17-3.71). In the 1016 individuals who underwent CABG, 402 (39.6%) underwent OPCAB and 614 (60.4%) undergoing ONCAB. When TTFM and HFUS were utilized, OPCAB resulted in greater number of strategy changes for aortic portion of the procedure (14.7% vs. 3.4%, OR 4.03, CI 2.32-7.20) without a difference in coronary target or graft revision. In the REQUEST study, in-hospital mortality was published at 0.6%. CONCLUSIONS TTFM use demonstrates a statistically significant impact on intra-operative decision making and operative strategy changes in patients with concomitant ESRD, DM and who are undergoing OPCAB relative to ONCAB. This difference in OPCAB vs. ONCAB may be related to higher mean graft flows in OPCAB in the setting of a standardized TTFM cutoff for determination of graft quality. This data cumulatively suggests there a role for TTFM in CABG, namely due to its positive impact on outcome and statistically significant impact on intra-operative decision making.
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Affiliation(s)
- John Kucera
- Department of Surgery, Walter Reed National Military Medical Center, Bethesda, MD, USA
| | - John Duggan
- Department of Surgery, Walter Reed National Military Medical Center, Bethesda, MD, USA
| | - Alex Peters
- Department of Surgery, Walter Reed National Military Medical Center, Bethesda, MD, USA
| | - Gregory Trachiotis
- Division of Cardiothoracic Surgery and Heart Center, Washington DC Veterans Affairs Medical Center, Washington, DC, USA.
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15
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Ji K, Han M, Yang M, Xu Q, Zhang Y. Integrated meta-analysis and network pharmacology analysis: evaluation of Zhigancao decoction as treatment for diabetic cardiomyopathy. Front Cardiovasc Med 2025; 12:1454647. [PMID: 40161384 PMCID: PMC11949964 DOI: 10.3389/fcvm.2025.1454647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 02/19/2025] [Indexed: 04/02/2025] Open
Abstract
Background Zhigancao Decoction (ZGCD) is derived from "Treatise on Febrile Diseases" and is traditionally prescribed for treating a variety of cardiovascular conditions. As of now, there are no data to support its use as a treatment for diabetic cardiomyopathy (DCM) and the mechanism behind the effect is unclear as well. In the present study, clinical evidence for the efficacy of ZGCD in patients with DCM was examined using a meta-analysis and its underlying anti-DCM molecular mechanisms were explored via network pharmacology. Methods The current study utilized an extensive search strategy encompassing various domestic and foreign databases databases to retrieve pertinent articles published up to June 2024. In light of this, a thorough evaluation of the benefits and safety of Zhigancao decoction (ZGCD) was conducted in this study using RevMan and Stata. Subsequently, a number of active compounds and target genes for ZGCD were gathered from the TCMSP and BATMAN-TCM databases, while the main targets for DCM were obtained from databases such as GenCards, OMIM, TTD, and DrugBank. To select core genes, protein-protein interaction networks were generated using the STRING platform, and enrichment analyses were completed using the Metascape platform. Results Meta-analysis results were ultimately derived from 9 studies involving 661 patients in total. In comparison with WM therapy alone, the pooled results showed that ZGCD significantly enhanced overall effectiveness. Additionally, the utilization of ZGCD was leading to a reduction in LVEDV, LVESV and LVDD, also a greater increase in LVEF. Meanwhile, the utilization of ZGCD during intervention was more effective in reducing SBP, and DBP. In addition, the ZGCD showed potential in reducing the occurrence of adverse events. In the context of network pharmacology, five constituents of ZGCD-namely lysine, quercetin, gamma-aminobutyric acid, stigmasterol, and beta-sitosterol-are posited to exert anti-diabetic cardiomyopathy (anti-DCM) effects through interactions with the molecular targets ASS1, SERPINE1, CACNA2D1, AVP, APOB, ICAM1, EGFR, TNNC1, F2, F10, IGF1, TNNI2, CAV1, INSR, and INS. The primary mechanisms by which ZGCD may achieve its anti-DCM effects are likely mediated via the AGEs/RAGE signaling pathway, as well as through pathways related to lipid metabolism and atherosclerosis. Conclusion In comparison to WM therapy alone, ZGCD demonstrates greater efficacy and safety in the management of DCM. ZGCD not only significantly reduces blood pressure, but also enhances cardiac function while producing fewer adverse effects. The therapeutic effects of ZGCD on DCM can likely be ascribed to its capacity to modulate the AGEs-RAGE signaling pathway, as well as its efficacy in enhancing lipid metabolism and mitigating atherosclerosis. Systematic Review Registration identifier (INPLASY202430133).
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Affiliation(s)
- Kangshou Ji
- First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, China
- Department of Cardiovascular Medicine, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Meizi Han
- National Key Laboratory of Chinese Medicine Modernization, Heilongjiang University of Traditional Chinese Medicine, Harbin, China
| | - Mingqian Yang
- Chinese Medicine College, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Qian Xu
- First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Yan Zhang
- First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, China
- Department of Cardiovascular Medicine, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
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Xu C, Lai YW, Chou SH, Zhang X, Koh ET, Dalan R, Leong KP. Association between bone mineral density and vascular health in rheumatoid arthritis. Singapore Med J 2025; 66:147-153. [PMID: 40116061 PMCID: PMC11991073 DOI: 10.4103/singaporemedj.smj-2024-183] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 02/02/2025] [Indexed: 03/23/2025]
Abstract
INTRODUCTION Rheumatoid arthritis (RA) is associated with heightened cardiovascular disease and increased susceptibility to osteoporosis, with shared underlying mechanisms. This study aimed to investigate the association between vascular function and bone mineral density (BMD). METHODS We conducted a cross-sectional study of 49 patients with RA at Tan Tock Seng Hospital, Singapore. Endothelial function was measured as reactive hyperaemia index (RHI)-endothelial peripheral arterial tonometry and aortic stiffness as carotid-femoral pulse wave velocity (cf-PWV) using SphygmoCor. Univariable and multivariable linear regression analyses were performed to evaluate the associations between BMD and vascular function. We used natural logarithm RHI (lnRHI) and cf-PWV as response variables, and each BMD as covariate, adjusting for body mass index, positive anti-cyclic citrullinated peptide, cumulative prednisolone dose, hydroxychloroquine use and Systematic COronary Risk Evaluation 2. RESULTS We recruited 49 patients (mean age 61.08 ± 8.20 years), of whom 44 (89.80%) were women and 39 (81.25%) were Chinese. Significant associations were found between lnRHI and BMD at the lumbar spine (β = 0.4289, P = 0.037) and total hip (β = 0.7544, P = 0.014) in univariable analyses. Multivariable analyses confirmed these associations, showing that lower BMD at the lumbar spine (β = 0.7303, P = 0.001), femoral neck (β = 0.8694, P = 0.030) and total hip (β = 0.8909, P = 0.010) were significantly associated with worse lnRHI. No significant associations were found between BMD and cf-PWV. CONCLUSION Lower BMD is associated with endothelial dysfunction, but not aortic stiffness in patients with RA. Further longitudinal studies are needed to confirm these associations and understand the underlying mechanisms.
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Affiliation(s)
- Chuanhui Xu
- Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Yi Wye Lai
- Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore
| | - Shih-Huan Chou
- Department of Endocrinology, Tan Tock Seng Hospital, Singapore
| | - Xiaoe Zhang
- Clinical Research and Innovation Office, Tan Tock Seng Hospital, Singapore
| | - Ee Tzun Koh
- Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore
| | - Rinkoo Dalan
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
- Department of Endocrinology, Tan Tock Seng Hospital, Singapore
| | - Khai Pang Leong
- Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore
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Schnetzer L, Leiherer A, Festa A, Mündlein A, Plattner T, Mayer G, Saely C, Drexel H. Type 2 diabetes and chronic kidney disease as long-term predictors of cardiovascular events in patients with coronary artery disease. Eur J Clin Invest 2025; 55:e14374. [PMID: 39704124 DOI: 10.1111/eci.14374] [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: 10/10/2024] [Accepted: 12/10/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND Both chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) confer a high risk of cardiovascular disease and mortality. These entities frequently coincide. The separate and joint impact of CKD and T2DM on the risk of major cardiovascular events (MACE) and survival is unclear. METHODS In this prospective cohort study, patients with angiographically proven coronary artery disease were investigated according to their CKD and T2DM status (T2DM-/CKD-, T2DM+/CKD-, T2DM-/CKD+, T2DM+/CKD+) and followed for up to 18 years. RESULTS A total of 1441 patients were included in the study of whom 39% experienced MACE (T2DM-/CKD-: 31%, T2DM+/CKD-: 43%, T2DM-/CKD+: 53%, T2DM+/CKD+: 61%) and 53% died. A log-rank test revealed significant differences between the event-free time period of the four groups (χ2 (3) = 112.57, p < 0.001). The presence of T2DM and CKD was associated with a 2.72-fold increase [1.98-3.73] in MACE compared to patients who suffered from neither condition (p < 0.001). T2DM alone led to a 1.37-fold increase [1.1-1.7], (p = 0.004), CKD alone to a 1.71-fold increase [1.31-2.25], (p < 0.001). CONCLUSION T2DM and CKD in patients with coronary artery disease are mutually independent predictors of cardiovascular events. Patients with both CKD and T2DM are at an extremely high risk for cardiovascular events.
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Affiliation(s)
- Laura Schnetzer
- Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria
| | - Andreas Leiherer
- Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria
- Private University in the Principality of Liechtenstein, Triesen, Liechtenstein
- Medical Central Laboratories, Feldkirch, Austria
| | - Andreas Festa
- Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria
- Private University in the Principality of Liechtenstein, Triesen, Liechtenstein
| | - Axel Mündlein
- Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria
- Private University in the Principality of Liechtenstein, Triesen, Liechtenstein
- Medical Central Laboratories, Feldkirch, Austria
| | - Thomas Plattner
- Medicine I, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
| | - Gert Mayer
- Department of Internal Medicine IV-Nephrology and Hypertension, Medical University of Innsbruck, Innsbruck, Austria
| | - Christoph Saely
- Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria
- Private University in the Principality of Liechtenstein, Triesen, Liechtenstein
- Medicine I, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
| | - Heinz Drexel
- Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria
- Private University in the Principality of Liechtenstein, Triesen, Liechtenstein
- Vorarlberger Landeskrankenhausbetriebsgesellschaft, Feldkirch, Austria
- Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
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Baty M, Chimoriya R, James S, Kritharides L, Behdasht S, Suryawanshi A, Aitken SJ. Diabetes in Peripheral Artery Disease: Prevalence, Complications, and Polypharmacy. J Clin Med 2025; 14:1383. [PMID: 40004919 PMCID: PMC11856835 DOI: 10.3390/jcm14041383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 02/07/2025] [Accepted: 02/14/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Patients with peripheral artery disease (PAD) and diabetes face high risks of comorbidities, tissue loss, and cardiovascular events. As global type 2 diabetes (T2DM) prevalence rises, so does its incidence in symptomatic patients with PAD, though this population is under-studied in Australia. This cross-sectional analysis sought to characterize PAD patients with diabetes regarding prevalence, major complications, medication use, and prescribing patterns, comparing them to non-diabetic PAD patients. We also examined PAD complications in relation to diabetic control. Methods: This cross-sectional study looked at the baseline data from 105 PAD participants in the TEAM-PAD randomized controlled trial that were analyzed using descriptive statistics, prevalence odds ratios and regression analysis. Participants were recruited between June 2023 and August 2024 from public clinics, private surgeons, and Concord Repatriation General Hospital, Sydney. Results: Diabetes prevalence was 52.83% (n = 56) with 29.5% (n = 31) of participants with T2DM having uncontrolled hyperglycemia (HbA1c ≥ 7%), which was weakly negatively correlated with age (r = -0.372, p = 0.039). Participants with T2DM were twice as likely to have a history of coronary artery disease (POR 2.43; 95% with a 95% confidence interval (CI) between 1.09-5.43, and over three times as likely to have tissue loss (POR 3.39; 95% CI 1.22-9.43). The odds of polypharmacy (≥5 medications) were 10 times greater in participants with T2DM (POR 10.8; 95% CI 2.31-50.4), affecting 96.4% of this group. Conclusions: Diabetes prevalence and associated complications were higher than previous estimates, underscoring the challenges in managing diabetes and polypharmacy in participants with PAD. A multidisciplinary approach may improve outcomes.
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Affiliation(s)
- Mason Baty
- Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia
| | - Ritesh Chimoriya
- Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia
- Concord Institute of Academic Surgery, Concord Repatriation General Hospital, Concord, NSW 2139, Australia
| | - Sophie James
- Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia
- Concord Institute of Academic Surgery, Concord Repatriation General Hospital, Concord, NSW 2139, Australia
| | - Leonard Kritharides
- Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia
- Department of Cardiology, Concord Hospital, The University of Sydney, 1 Hospital Road, Concord, NSW 2139, Australia
| | - Samim Behdasht
- Department of Pharmacy, Concord Repatriation General Hospital, Concord, NSW 2139, Australia
| | - Avinash Suryawanshi
- Department of Endocrinology and Metabolism, Concord Repatriation General Hospital, Concord, NSW 2139, Australia
| | - Sarah J. Aitken
- Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia
- Concord Institute of Academic Surgery, Concord Repatriation General Hospital, Concord, NSW 2139, Australia
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19
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Geravandi S, Emamgholipour S, Pakdaman M, Sari AA, Esmaeili A. Principal components of type 2 diabetes risk: an exploratory factor analysis in an Iranian cohort. BMC Public Health 2025; 25:652. [PMID: 39962439 PMCID: PMC11834231 DOI: 10.1186/s12889-025-21814-4] [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: 10/04/2024] [Accepted: 02/06/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND The significance of interrelated risk factors for Type 2 diabetes (T2D) is not easily demonstrated by conventional statistical methods. This study aims to investigate the principal components of T2D risk by employing exploratory factor analysis in Iranian cohort. The analysis encompasses a range of sociodemographic, lifestyle, and health-related variables to uncover clusters of factors associated with the risk of T2D. METHODS Cross-sectional data of 1200 diabetic and 1200 nondiabetic Iranian adults was analyzed using STATA 14.2 (p < 0.05). Pearson's Chi-squared test was used to assess the difference between the two groups. Spearman correlation explored the relationships between variables. Separate factor analyses were conducted for diabetic, non-diabetic, and combined groups. Principal component analysis (PCA) identified the initial components. Crude and adjusted logistic regressions examined the associations between derived factors and T2D risk. RESULTS PCA identified eleven components with eigenvalues ≥ 1, accounting for 65.09% of the variance. Logistic regression analysis highlighted several significant associations with T2D risk. Positive associations were observed for PC1 ("drugs, smoking, and alcohol"), PC2 ("chronic diseases", including age, hypertension, dyslipidemia, and coronary heart disease), PC3 ("lipids", such as triglycerides, cholesterol, and low-density lipoprotein), PC4 ("body mass", including BMI, waist circumference, and waist-to-hip ratio), PC5 ("gestational-related risks", such as gestational diabetes and gestational hypertension), and PC6 ("glucose/lipid factors", including fasting glucose, triglycerides, and an inverse relationship with high-density lipoprotein). Conversely, negative associations with T2D risk were found for PC7 ("socioeconomic factors", such as socioeconomic status and education), PC8 (inverse association with age, along with fatty liver, thyroid disorders, and low waist-to-hip ratio), and PC10 (marital status, sleep duration, low fasting glucose, lower age, and an inverse association with fatty liver). CONCLUSIONS Key metabolic clusters, including "Lipids", "Body Mass", "Chronic Diseases", and "Glucose/Lipid" align with previous findings. These results underscore the multifactorial and interconnected nature of T2D risk, highlighting underlying physiological processes.
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Affiliation(s)
- Sara Geravandi
- Department of Health Management, policy and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Sara Emamgholipour
- Department of Health Management, policy and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
- Non communicable disease research center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mohsen Pakdaman
- Health Policy and Management Research Centre, Department of HealthCare Management, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Ali Akbari Sari
- Department of Health Management, policy and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Esmaeili
- Department of Emergency Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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20
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Gregg EW, Holman N, Sophiea M, Misra S, Pearson-Stuttard J, Valabhji J, Khunti K. Multiple long-term conditions as the next transition in the global diabetes epidemic. COMMUNICATIONS MEDICINE 2025; 5:42. [PMID: 39953177 PMCID: PMC11828996 DOI: 10.1038/s43856-025-00742-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 01/15/2025] [Indexed: 02/17/2025] Open
Abstract
Several transitions, or new patterns and dynamics in the contributors and health outcomes, have altered the character and burden of the multi-decade, worldwide growth in prevalence of type 2 diabetes (T2DM). These changes have led to different needs for prevention and care. These dynamics have been driven by diverse demographic, socio-economic, behavioural, and health system response factors. In this Perspective, we describe these transitions and how their attributes have set the stage for multimorbidity, or multiple long-term conditions (MLTCs), to be the next major challenge in the diabetes epidemic. We also describe how the timing and character of these stages differ in high-, middle-, and low-income countries. These challenges call for innovation and a stronger focus on MLTCs across the spectrum of cause, effectiveness, and implementation studies to guide prevention and treatment priorities.
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Affiliation(s)
- Edward W Gregg
- School of Population Health, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
- School of Public Health, Imperial College London, London, UK.
| | - Naomi Holman
- School of Population Health, RCSI University of Medicine and Health Sciences, Dublin, Ireland
- School of Public Health, Imperial College London, London, UK
- NHS England, Wellington House, London, UK
| | - Marisa Sophiea
- School of Public Health, Imperial College London, London, UK
| | - Shivani Misra
- Department of Diabetes and Endocrinology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
- Division of Metabolism, Digestion & Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | | | - Jonathan Valabhji
- NHS England, Wellington House, London, UK
- Division of Metabolism, Digestion & Reproduction, Faculty of Medicine, Imperial College London, London, UK
- Chelsea & Westminster Hospital NHS Foundation Trust, London, UK
| | - Kamlesh Khunti
- Diabetes Research Centre, University of Leicester, Leicester, UK
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21
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Lai CC, Chang BCC, Hwang LC. Presence of coronary artery disease in adults with newly detected diabetes mellitus. BMC Cardiovasc Disord 2025; 25:76. [PMID: 39901120 PMCID: PMC11789286 DOI: 10.1186/s12872-024-04463-0] [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: 06/28/2023] [Accepted: 12/30/2024] [Indexed: 02/05/2025] Open
Abstract
PURPOSE We aimed to analyze the presence and extent of coronary artery disease in patients with newly detected diabetes mellitus. METHODS Clinical health examinations of asymptomatic community-dwelling adults between 2008 and 2018 at a medical center in Taiwan were reviewed. Coronary computed tomography angiography was performed in 444 participants, of which 338, 54, and 52 were categorized as 'without diabetes mellitus', 'newly detected diabetes mellitus', and 'known diabetes mellitus', respectively. RESULTS Prevalence of significant coronary artery disease (≥ 50% stenosis) was higher in participants with newly detected diabetes mellitus than in participants without diabetes mellitus (40.7% vs. 20.1%, p < 0.0001). Among those with coronary artery stenosis, the number of coronary vessels with significant obstruction (0.72 vs. 0.42, p = 0.0147) was also higher in participants with newly detected diabetes mellitus. Using multiple logistic regression analysis, new detection of diabetes mellitus was identified as an independent risk factor for significant coronary artery disease (odds ratio: 2.153, 95% confidence interval: 1.112-4.166). CONCLUSION Asymptomatic patients with newly detected diabetes mellitus had higher prevalence and greater extent of coronary artery disease than those without diabetes mellitus. More attention should thus be paid to the assessment of coronary artery disease in patients with newly detected diabetes mellitus.
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Affiliation(s)
- Cheng-Chien Lai
- Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | | | - Lee-Ching Hwang
- Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
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22
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Xia T, Yu J, Du M, Chen X, Wang C, Li R. Vascular endothelial cell injury: causes, molecular mechanisms, and treatments. MedComm (Beijing) 2025; 6:e70057. [PMID: 39931738 PMCID: PMC11809559 DOI: 10.1002/mco2.70057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 12/16/2024] [Accepted: 12/17/2024] [Indexed: 02/13/2025] Open
Abstract
Vascular endothelial cells form a single layer of flat cells that line the inner surface of blood vessels, extending from large vessels to the microvasculature of various organs. These cells are crucial metabolic and endocrine components of the body, playing vital roles in maintaining circulatory stability, regulating vascular tone, and preventing coagulation and thrombosis. Endothelial cell injury is regarded as a pivotal initiating factor in the pathogenesis of various diseases, triggered by multiple factors, including infection, inflammation, and hemodynamic changes, which significantly compromise vascular integrity and function. This review examines the causes, underlying molecular mechanisms, and potential therapeutic approaches for endothelial cell injury, focusing specifically on endothelial damage in cardiac ischemia/reperfusion (I/R) injury, sepsis, and diabetes. It delves into the intricate signaling pathways involved in endothelial cell injury, emphasizing the roles of oxidative stress, mitochondrial dysfunction, inflammatory mediators, and barrier damage. Current treatment strategies-ranging from pharmacological interventions to regenerative approaches and lifestyle modifications-face ongoing challenges and limitations. Overall, this review highlights the importance of understanding endothelial cell injury within the context of various diseases and the necessity for innovative therapeutic methods to improve patient outcomes.
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Affiliation(s)
- Tian Xia
- Department of Laboratory MedicineThe First Medical Center of Chinese PLA General HospitalBeijingChina
- Department of Laboratory MedicineMedical School of Chinese PLABeijingChina
| | - Jiachi Yu
- Department of Laboratory MedicineThe First Medical Center of Chinese PLA General HospitalBeijingChina
- Department of Laboratory MedicineMedical School of Chinese PLABeijingChina
| | - Meng Du
- Department of Laboratory MedicineThe First Medical Center of Chinese PLA General HospitalBeijingChina
- Department of Clinical LaboratoryHuaian Hospital of Huaian CityHuaianJiangsuChina
| | - Ximeng Chen
- Department of Laboratory MedicineThe First Medical Center of Chinese PLA General HospitalBeijingChina
- Department of Laboratory MedicineMedical School of Chinese PLABeijingChina
| | - Chengbin Wang
- Department of Laboratory MedicineThe First Medical Center of Chinese PLA General HospitalBeijingChina
- Department of Laboratory MedicineMedical School of Chinese PLABeijingChina
| | - Ruibing Li
- Department of Laboratory MedicineThe First Medical Center of Chinese PLA General HospitalBeijingChina
- Department of Laboratory MedicineMedical School of Chinese PLABeijingChina
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23
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Zhou JX, Zheng ZY, Peng ZX, Ni HG. Global impact of PM 2.5 on cardiovascular disease: Causal evidence and health inequities across region from 1990 to 2021. JOURNAL OF ENVIRONMENTAL MANAGEMENT 2025; 374:124168. [PMID: 39837142 DOI: 10.1016/j.jenvman.2025.124168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 12/31/2024] [Accepted: 01/15/2025] [Indexed: 01/23/2025]
Abstract
PM2.5 is an important environmental risk factor for cardiovascular disease (CVD) and poses a threat to global health. This study combines bibliometric analysis, Mendelian randomization (MR), and Global Burden of Disease (GBD) data to comprehensively explore the relationship between PM2.5 exposure and CVD. MR analyses provided strong evidence for causality, reinforcing findings from traditional observational studies. The estimated global burden of PM2.5-related CVD indicated, that there exist significant impacts on the elderly, men, and populations in low and medium socio-demographic index (SDI) areas. This study further found that population growth and aging are the main drivers of this burden with large inequities, although medical advances have mitigated some of the effects. Overall, the opportunity to reduce the burden of CVD remains significant, particularly in medium SDI countries. Projections to 2045 suggested that the absolute burden will increase, while age-standardized rates will decline due to improvements in air quality and health care. These findings emphasized the urgent need for targeted interventions to mitigate the deleterious effects of PM2.5 on global cardiovascular health and to address health inequalities between regions.
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Affiliation(s)
- Jing-Xuan Zhou
- School of Urban Planning and Design, Peking University Shenzhen Graduate School, Shenzhen, 518055, China
| | - Zi-Yi Zheng
- School of Urban Planning and Design, Peking University Shenzhen Graduate School, Shenzhen, 518055, China
| | - Zhao-Xing Peng
- School of Urban Planning and Design, Peking University Shenzhen Graduate School, Shenzhen, 518055, China
| | - Hong-Gang Ni
- School of Urban Planning and Design, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
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24
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Bayrakçeken E, Yarali S, Ercan U, Alkan Ö. Patterns among factors associated with myocardial infarction: chi-squared automatic interaction detection tree and binary logit model. BMC Public Health 2025; 25:296. [PMID: 39849407 PMCID: PMC11760063 DOI: 10.1186/s12889-025-21536-7] [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: 02/16/2024] [Accepted: 01/19/2025] [Indexed: 01/25/2025] Open
Abstract
BACKGROUND Although mortality from myocardial infarction (MI) has declined worldwide due to advancements in emergency medical care and evidence-based pharmacological treatments, MI remains a significant contributor to global cardiovascular morbidity. This study aims to examine the risk factors associated with individuals who have experienced an MI in Türkiye. METHODS Microdata obtained from the Türkiye Health Survey conducted by Turkish Statistical Institute in 2019 were used in this study. Binary logistic regression, Chi-Square, and CHAID analyses were conducted to identify the risk factors affecting MI. RESULTS The analysis identified several factors associated with an increased likelihood of MI, including hyperlipidemia, hypertension, diabetes, chronic disease status, male gender, older age, single marital status, lower education level, and unemployment. Marginal effects revealed that elevated hyperlipidemia levels increased the probability of MI by 4.6%, while the presence of hypertension, diabetes, or depression further heightened this risk. Additionally, individuals with chronic diseases lasting longer than six months were found to have a higher risk of MI. In contrast, factors such as being female, having higher education, being married, being employed, engaging in moderate physical activity, and moderate alcohol consumption were associated with a reduced risk of MI. CONCLUSION To prevent MI, emphasis should be placed on enhancing general education and health literacy. There should be a focus on increasing preventive public health education and practices to improve variables related to healthy lifestyle behaviours, such as diabetes, hypertension, and hyperlipidemia.
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Affiliation(s)
- Esra Bayrakçeken
- Department of Medical Services and Techniques, Vocational School of Health Services, Ataturk University, Erzurum, Türkiye
| | - Süheyla Yarali
- Department of Public Health Nursing, Faculty of Nursing, Ataturk University, 2 Floor, No: 49, Erzurum, Türkiye
| | - Uğur Ercan
- Department of Informatics, Akdeniz University, 1st Floor, Number: CZ-20, Antalya, Türkiye
| | - Ömer Alkan
- Department of Econometrics, Faculty of Economics and Administrative Sciences, Ataturk University, 2nd Floor, Number: 222, Erzurum, Türkiye.
- Master Araştırma Eğitim ve Danışmanlık Hizmetleri Ltd. Şti., Ata Teknokent, Erzurum, TR-25240, Türkiye.
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25
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Mader A, Haeberli D, Larcher B, Dopheide JF, Saely CH, Heinzle CF, Amann P, Schindewolf M, Festa A, Drexel H. Contribution of type 2 diabetes to major adverse cardiovascular events (MACE) in a long-term observational study with different stages of atherosclerosis. Sci Rep 2025; 15:2792. [PMID: 39843486 PMCID: PMC11754429 DOI: 10.1038/s41598-024-84985-x] [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: 04/24/2024] [Accepted: 12/30/2024] [Indexed: 01/24/2025] Open
Abstract
The impact of diabetes on incident cardiovascular disease in relation to the extent of atherosclerotic disease remains unclear. We aimed to investigate major adverse cardiovascular events (MACE) in patients with or without type 2 diabetes (T2DM) presenting with two extremes of atherosclerotic disease, those with angiographically documented minor coronary atherosclerotic lesions and those with symptomatic peripheral artery disease. We included 1238 patients from two prospective, long-term cohort studies. Patients underwent coronary angiography and/or sonography in order to assess the grade of atherosclerosis and were defined as having no signs of Atherosclerosis (n = 332; Group I), minor atherosclerosis (n = 425; Group II) and major atherosclerosis (n = 481; Group III). Cardiovascular events were recorded over a median follow-up period of 7.1 years (Q1 = 3.6 years, Q2 = 7.1 years, Q3 = 11.3 years), covering a total of 9533 patient years. We tested the hypothesis that T2DM infers the same relative risk increase irrespective of the atherosclerosis stage, considering 3-point MACE as the primary endpoint. Incident MACE was reported in 681 patients (51%). MACE occurred more frequently in patients with T2DM than in patients without T2DM (p < 0.001). Further, MACE occurred more frequently in group III (58.1%), than group II (34.1%) or group I (19.1%) (group I vs. group II vs. group III, p < 0.001). In a cox-regression-model, T2DM was a significant predictor of MACE in univariate analyses (HR = 2.43 [1.88-3.14], p < 0.001) and after multivariate adjustment for cardiovascular risk factors, as well as the different grades of atherosclerosis (HR = 1.37 [1.02-1.84], p = 0.034). Also, atherosclerosis grades predicted MACE (HR = 3.19 [2.75-3.70], p < 0.001) in univariate analyses, and also after multivariate adjustment for known cardiovascular risk factors, including T2DM (HR = 1.61 [1.31-1.98], p < 0.001). Finally, when testing for interactions between T2DM and stages of atherosclerosis on MACE we could not find any significant interaction (HR = 1.14 [0.86-1.52], p = 0.364). We conclude that T2DM infers an increased risk for MACE across anatomically and morphologically distinct stages of atherosclerosis.
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Affiliation(s)
- Arthur Mader
- VIVIT-Institute, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
- Medicine I, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
| | | | - Barbara Larcher
- VIVIT-Institute, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
- Medicine I, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
| | - Jörn F Dopheide
- VIVIT-Institute, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
- Angiology, Spital Thun, Thun, Switzerland
| | - Christoph H Saely
- VIVIT-Institute, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
- Medicine I, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
- Private University of the Principality of Liechtenstein, Triesen, Liechtenstein
| | | | - Peter Amann
- VIVIT-Institute, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
| | - Marc Schindewolf
- Angiology, Inselspital Bern, Bern, Switzerland
- Clincal Investigation Unit, Inselspital, Bern, Switzerland
| | - Andreas Festa
- VIVIT-Institute, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
- Private University of the Principality of Liechtenstein, Triesen, Liechtenstein
| | - Heinz Drexel
- VIVIT-Institute, Academic Teaching Hospital Feldkirch, Feldkirch, Austria
- Private University of the Principality of Liechtenstein, Triesen, Liechtenstein
- Vorarlberger Landeskrankenhausbetriebsgesellschaft, Feldkirch, Austria
- Drexel University College of Medicine, Philadelphia, PA, USA
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26
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Zhang Y, Li Z, Hao Y. Comparative efficacy of GLP-1 RAs/SGLT-2 inhibitors in reducing cardiovascular events in type 2 diabetes according to baseline use of metformin: a systematic review and meta-analysis of randomized controlled trials. Eur J Med Res 2025; 30:13. [PMID: 39773332 PMCID: PMC11706166 DOI: 10.1186/s40001-024-02241-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 12/19/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Sodium-glucose transporters 2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are recommended along with metformin for the potential cardiovascular benefits among type 2 diabetes. This meta-analysis aims to evaluate whether the effects of SGLT-2i or GLP-1 RAs on cardiovascular outcomes are consistent with and without baseline metformin use. METHODS PubMed, Cochrane, Web of Science and Embase were searched for randomized placebo-controlled trials with SGLT-2i or GLP-1 RAs as interventions of type 2 diabetes patients up to June, 2024. The main outcomes were major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF) or cardiovascular death. Both random-effects model and fixed model were adopted to estimate pooled hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS A total of 81,738 patients (median age: 62-66 years, 53.7-71.5% men, median follow-up: 1.3-5.4 years) from 11 studies (7 studies of SGLT-2i and 4 of GLP-1 RAs) were included in the study. The metformin-naive portions ranged from 28.90% to 81.98%. Among patients using metformin at baseline, SGLT-2i or GLP-1 RAs reduced MACE risk (HR = 0.95, 95% CI 0.91-0.99, P = 0.02). In metformin-naive patients, similar reductions were observed (HR = 0.79, 95% CI 0.65-0.95, P = 0.01). No statistically significant interaction was found between metformin users and non-users for any outcome (all P values for interaction > 0.05), indicating consistent cardiovascular benefits regardless of baseline metformin therapy. CONCLUSIONS SGLT-2i and GLP-1 RAs have the effects of cardiovascular benefits for T2DM patients regardless of baseline metformin use.
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Affiliation(s)
- Yuxin Zhang
- Center for Clinical and Epidemiologic Research, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China
| | - Zhaoji Li
- Peking University Third Hospital, Beijing, China
| | - Yongchen Hao
- Center for Clinical and Epidemiologic Research, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China.
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27
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Bilal A, Pratley R. Diabetes and cardiovascular disease in older adults. Ann N Y Acad Sci 2025; 1543:42-67. [PMID: 39666834 DOI: 10.1111/nyas.15259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
An aging population combined with a rapidly increasing prevalence of diabetes foreshadows a global epidemic of cardiovascular and kidney disease that threatens to halt improvements in life and health-span and will have particularly severe consequences in older adults. The management of diabetes has been transformed with the recent development of newer anti-hyperglycemic agents that have demonstrated superior efficacy. However, the utility of these drugs extends beyond glycemic control to benefits for managing obesity, cardiovascular disease (CVD), chronic kidney disease, and heart failure. Numerous cardiovascular and kidney outcomes trials of these drugs have played an instrumental role in shaping current guidelines for the management of diabetes and CVD. Older adults with diabetes are diverse in terms of their comorbidities, diabetic complications, and cognitive and functional status. Therefore, there is an unmet need for personalized management of diabetes and CVD in this population. In this review, we provide an overview of the epidemiological burden and management of diabetes and CVD in older adults. We then focus on randomized cardiovascular and kidney outcome trials with anti-hyperglycemic agents to propose an evidence-based approach to the management of diabetes in older adults with high risk of cardiovascular and kidney disease.
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Affiliation(s)
- Anika Bilal
- AdventHealth Translational Research Institute, Orlando, Florida, USA
| | - Richard Pratley
- AdventHealth Translational Research Institute, Orlando, Florida, USA
- AdventHealth Diabetes Institute, Orlando, Florida, USA
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28
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Park SS, Koo BK, Park S, Han K, Moon MK. Impact of New-Onset Diabetes after Transplantation on Cardiovascular Risk and Mortality in Korea: A Nationwide Population-Based Study. Diabetes Metab J 2025; 49:117-127. [PMID: 39262290 PMCID: PMC11788551 DOI: 10.4093/dmj.2024.0078] [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: 02/18/2024] [Accepted: 06/17/2024] [Indexed: 09/13/2024] Open
Abstract
BACKGRUOUND Limited data are available on the adverse effects of new-onset diabetes after transplantation (NODAT) in solid organ transplantation (TPL) other than kidney. This study aimed to identify the risk of complications associated with NODAT in recipients of kidney, liver, or heart TPL. METHODS Using the Korean National Health Insurance Service database, recipients of kidney, liver, or heart TPL between 2009 and 2015 were identified. The incidence of coronary artery disease (CAD), cerebrovascular accident (CVA), and malignancy was compared across groups with NODAT, pretransplant diabetes mellitus (DM), and without DM using Cox regression analysis. RESULTS A total of 9,632 kidney, liver, or heart TPL recipients were included. During the median follow-up of 5.9 years, NODAT independently increased the incidence of CAD (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.39 to 4.30) and overall mortality (HR, 1.48; 95% CI, 1.14 to 1.95) compared to the reference group even after adjustment for confounders; this was more prominent in kidney TPL than in liver TPL. The risk of CVA was significantly increased by pretransplant DM but not by NODAT in both kidney and liver TPL (HR, 2.47; 95% CI, 1.68 to 3.65; and HR, 3.18; 95% CI, 1.07 to 9.48, respectively). NODAT increased the risk of malignancy in the crude model, which lost its statistical significance after confounder adjustment. CONCLUSION NODAT independently increases the risk of CAD and mortality after TPL, which is more evident in kidney recipients. There was no additional increased risk of CVA or malignancy with NODAT in solid organ TPL.
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Affiliation(s)
- Seung Shin Park
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Bo Kyung Koo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Sanghyun Park
- Department of Medical Statistics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
| | - Min Kyong Moon
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
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Zhao Y, D’Agostino RB, Malik S, Watson KE, Bertoni AG, Budoff MJ, Cain L, Correa A, Folsom AR, Jacobs DR, Selvin E, Wong ND. United States Pooled Cohort Cardiovascular Disease Risk Scores in Adults With Diabetes Mellitus. JACC. ADVANCES 2025; 4:101448. [PMID: 39759441 PMCID: PMC11699612 DOI: 10.1016/j.jacadv.2024.101448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 10/07/2024] [Accepted: 10/23/2024] [Indexed: 01/07/2025]
Abstract
Background There is significant heterogeneity in cardiovascular disease (CVD) risk among patients with diabetes mellitus (DM). Objectives The purpose of this study was to develop risk scores for total CVD and its components from a contemporary pooled, observational cohort of U.S. adults with DM. Methods CVD-free adults with DM aged 40 to 79 years were pooled from 4 U.S. population-based cohorts (CARDIA [Coronary Artery Risk Development in Young Adults], Framingham Offspring, Jackson Heart Study, and the MESA (Multiethnic Study of Atherosclerosis) studied since 2000. Baseline DM-specific and non-DM-specific CVD risk factors were evaluated as predictors. We developed 10-year DM Risk Scores (DMRS) for total CVD, atherosclerotic CVD (ASCVD), coronary heart disease (CHD), heart failure (HF) and stroke. Score performance was validated internally and externally. Results We included 2,174 adults with DM mean age 59.2 ± 10.5 years, 55.4% female and 47.5% Black followed up to 10 years. Age, sex, HbA1c, creatinine, systolic blood pressure, DM medication, and smoking were the most important predictors. The DMRS had good internal discrimination (c-statistics 0.72, 0.72, 0.72, 0.79 and 0.73 for CVD, ASCVD, CHD, HF, and stroke) and calibration (calibration slopes 0.93, 0.95, 0.93, 0.98, and 0.89 for CVD, ASCVD, CHD, HF, and stroke; Greenwood Nam-D'Agostino calibration tests were significant for CHD (P < 0.01) and CVD (P < 0.05) but not for ASCVD, HF, and stroke). From external validation in 2 other cohorts, the DMRS outperformed current risk scores. Conclusions Our U.S. pooled cohort DMRS for predicting CVD events demonstrated good predictive performance for assessing CVD risk in adults with DM.
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Affiliation(s)
- Yanglu Zhao
- Department of Epidemiology, University of California, Los Angeles, California, USA
- Mary and Steve Wen Cardiovascular Division, Department of Medicine, University of California-Irvine, Irvine, California, USA
| | | | - Shaista Malik
- Mary and Steve Wen Cardiovascular Division, Department of Medicine, University of California-Irvine, Irvine, California, USA
| | - Karol E. Watson
- Department of Epidemiology, University of California, Los Angeles, California, USA
| | - Alain G. Bertoni
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Matthew J. Budoff
- Division of Cardiology, Lundquist Institute, Torrance, California, USA
| | - Loretta Cain
- Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Adolfo Correa
- Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA
| | - Aaron R. Folsom
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
| | - David R. Jacobs
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
| | - Elizabeth Selvin
- Department of Epidemiology, John Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Nathan D. Wong
- Department of Epidemiology, University of California, Los Angeles, California, USA
- Mary and Steve Wen Cardiovascular Division, Department of Medicine, University of California-Irvine, Irvine, California, USA
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30
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Hu WS, Lin CL. Effect of anti-diabetic agent on interstitial lung disease in patients with diabetes mellitus. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:581-589. [PMID: 39031184 DOI: 10.1007/s00210-024-03296-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 07/10/2024] [Indexed: 07/22/2024]
Abstract
The objective was to assess the protective role of anti-diabetic agent (ADA) in predicting interstitial lung disease (ILD) among patients with diabetes mellitus (DM). We formed a cohort of DM patients between 2009 and 2016 using data from Taiwan. Univariable and multivariable Cox proportion hazards regression models were used to examine the effect of risk factor on the risk of developing ILD, presented as a hazard ratio (HR) with a 95% confidence interval (CI). Cox proportional hazard regression analysis for the risk of DM-associated ILD with joint effect of dipeptidyl peptidase-4 inhibitor (DPP4I), glucagon-like peptide-1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter 2 inhibitors (SGLT2I) showed that SGLT2I, GLP-1 RA, and DPP-4I had a decreased risk of ILD with adjusted HR of 0.14 (0.11, 0.18), 0.29 (0.24, 0.35), and 0.64 (0.62, 0.67), respectively. DPP4I, GLP-1 RA, and SGLT2I could be considered to be introduced to this DM population for ILD risk reduction in DM, especially with SGLT2I usage.
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Affiliation(s)
- Wei-Syun Hu
- School of Medicine, College of Medicine, China Medical University, Taichung, 40402, Taiwan.
- Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, 2, Yuh-Der Road, Taichung, 40447, Taiwan.
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, 40447, Taiwan
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Masutani N, Ogawa H, Soejima H, Okada S, Masuda I, Waki M, Jinnouchi H, Saito Y, Morimoto T. Long-Term Effects of Low-Dose Aspirin on Gastrointestinal Symptoms and Bleeding Complications in Patients with Type 2 Diabetes. Am J Cardiovasc Drugs 2025; 25:95-112. [PMID: 39340686 DOI: 10.1007/s40256-024-00679-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/23/2024] [Indexed: 09/30/2024]
Abstract
BACKGROUND Low-dose aspirin for primary prevention is determined by the balance of risks of cardiovascular events and adverse effects. We assessed the long-term gastrointestinal symptoms or bleeding with low-dose aspirin in diabetic patients. METHODS The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a randomized clinical trial to evaluate the efficacy and safety of low-dose aspirin in patients with type 2 diabetes. As a post hoc analysis, we investigated the incidence of upper gastrointestinal symptoms or bleeding in aspirin (100 mg enteric-coated aspirin or 81 mg buffered aspirin daily) and no-aspirin groups within and beyond 3 years. RESULTS Of 2535 patients (mean age 65 years, 55% male) followed for a median of 11.2 years, 1258 were included in the aspirin group (951 enteric-coated, 208 buffered, 99 unknown) and 1277 were included in the no-aspirin group. The cumulative incidence of upper gastrointestinal symptoms or bleeding was higher in the aspirin group than the no-aspirin group (8.8% vs. 5.7% at 18 years; p < 0.0001). The increased risk in the aspirin group was prominent within 3 years, and the hazard ratio (HR) [95% confidence interval (CI)] of the aspirin group was 7.10 [3.21-15.7], but attenuated beyond 3 years (HR 1.20 [0.76-1.89]). In 1159 patients in the aspirin group, the cumulative incidence was lower in the enteric-coated than in the buffered aspirin groups (2.9% vs. 7.3%; p = 0.003) within 3 years, and the adjusted HR of enteric-coated aspirin was 0.38 [0.20-0.72] compared with the buffered aspirin group. CONCLUSION The upper gastrointestinal symptoms or bleeding of low-dose aspirin within 3 years, and the aspirin formulations, were relevant for decision making of initiation and continuation of low-dose aspirin for primary prevention.
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Affiliation(s)
- Naoko Masutani
- Department of Data Science, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501, Japan
| | | | - Hirofumi Soejima
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences and Health Care Center, Kumamoto University, Kumamoto, Japan
| | - Sadanori Okada
- Center for Postgraduate Training, Nara Medical University, Kashihara, Japan
| | - Izuru Masuda
- Department of Endocrinology, Metabolism and Hypertension Research, Clinical Research Institute, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
| | - Masako Waki
- Food Safety Commission of Japan, Tokyo, Japan
| | - Hideaki Jinnouchi
- Department of Internal Medicine, Jinnouchi Hospital Diabetes Care Center, Kumamoto, Japan
| | - Yoshihiko Saito
- Department of Cardiovascular Medicine, Nara Prefecture Seiwa Medical Center, Ikoma, Japan
| | - Takeshi Morimoto
- Department of Data Science, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501, Japan.
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Higuchi Y, Kajiyama S, Kitta K, Miyawaki T, Matsumoto S, Ozasa N, Kajiyama S, Hashimoto Y, Fukui M, Imai S. Adding Lemon and n-3 PUFA-Rich Oil to Tomato Juice Preload to a Carbohydrate Meal Ameliorates Early Glycemic and Insulin Responses in Young Healthy Women: A Randomized Crossover Trial. J Nutr Sci Vitaminol (Tokyo) 2025; 71:133-139. [PMID: 40301054 DOI: 10.3177/jnsv.71.133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/01/2025]
Abstract
The aim was to evaluate the acute effect of drinking tomato juice preloaded with lemon and perilla oil 10 min before consuming carbohydrate on postprandial blood glucose, insulin, and lipids concentrations in young healthy women. In this randomized controlled crossover study, 21 women (age 21.1±0.6 y, HbA1c 5.2±0.2%, mean±SD) consumed either 200 g of tomato juice, tomato juice with 10 g of lemon juice and 5 g of perilla oil (n-3 PUFA-rich oil), or water 10 min before consuming 200 g of boiled white rice for 3 separate days. The energy and fat in tomato juice with lemon/n-3 PUFA-rich oil were higher (energy 402 kcal, fat 5.6 g) than tomato juice (354 kcal, 0.6 g) and water (315 kcal, 0.6 g). The blood parameters were measured at 0, 30, 60, and 120 min after carbohydrate consumption and compared among 3 d. The plasma glucose at 30 min in tomato juice with lemon/n-3 PUFA-rich oil was significantly lower than that of water (103.1±3.4 mg/dL vs. 127.8±4.0 mg/dL, p<0.001, mean±SE) and tended to be lower than that of tomato juice (113.9±4.9 mg/dL, p=0.078). The serum insulin at 30 min was also significantly lower in tomato juice with lemon/n-3 PUFA-rich oil than that of tomato juice (p<0.01). Adding lemon and n-3 PUFA-rich oil to tomato juice before carbohydrate meal can be practical method to lower early postprandial glucose and insulin responses in young healthy women.
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Affiliation(s)
- Yuki Higuchi
- Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University
| | - Shizuo Kajiyama
- Kajiyama Clinic
- Graduate School of Medical Science, Kyoto Prefectural University of Medicine
| | - Kaoru Kitta
- Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University
| | - Takashi Miyawaki
- Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University
| | - Shinya Matsumoto
- Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University
| | - Neiko Ozasa
- Graduate School of Medicine, Kyoto University
| | - Shintaro Kajiyama
- Kajiyama Clinic
- Graduate School of Medical Science, Kyoto Prefectural University of Medicine
| | - Yoshitaka Hashimoto
- Graduate School of Medical Science, Kyoto Prefectural University of Medicine
- Matsushita Memorial Hospital
| | - Michiaki Fukui
- Graduate School of Medical Science, Kyoto Prefectural University of Medicine
| | - Saeko Imai
- Department of Food and Nutrition, Faculty of Home Economics, Kyoto Women's University
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Ma Y, Gao H, Wu H. Comparison of adverse cardiovascular event endpoints between patients with diabetes and patients without diabetes based on coronary artery plaques: a systematic review and meta-analysis. J Cardiothorac Surg 2024; 19:672. [PMID: 39707525 DOI: 10.1186/s13019-024-03157-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 11/29/2024] [Indexed: 12/23/2024] Open
Abstract
BACKGROUND The classification of major adverse cardiovascular event (MACE) endpoints in patients with type 2 diabetes mellitus (T2DM) and either confirmed coronary artery disease (CAD) or high CAD risk, as well as the extent of the association between T2DM and coronary plaque characteristics, remains uncertain. PURPOSE This meta-analysis aims to compare MACE endpoints between patients with diabetes and patients without diabetes based on coronary artery plaques. METHODS We searched studies from Web of Science, PubMed, Embase, and the Cochrane Library up until September 1, 2023. Two independent researchers evaluated the quality and bias of the included studies. We used odds ratio (OR) and standardized mean difference (SMD) with 95% confidence interval (CI) to assess the effect of individual lesion parameters and coronary artery plaque characteristics on MACE endpoints. RESULTS Seven studies covered 1218 patients with diabetes and 3038 patients without diabetes. The follow-up time ranged from 2 to 5.4 years. The pooled results indicated that in all CAD lesions, DM was more strongly associated with MACE, myocardial infarction (MI), revascularization, and rehospitalization for unstable or progressive angina. The pooled OR was 1.82 (95% CI: 1.42 to 2.33, I2 = 0%, P < 0.00001) for MACE, 2.36 (95% CI: 1.47 to 3.79, I2 = 0%, P = 0.0004) for MI, 1.83 (95% CI: 1.33 to 2.53, I2 = 0%, P = 0.0002) for revascularization, and 1.65 (95% CI: 1.20 to 2.27, I2 = 0%, P = 0.002) for rehospitalization respectively. Subgroup analysis of culprit lesions (CLs) revealed significant differences between DM and non-DM for MACE, MI, revascularization, and stent thrombosis. While non-culprit lesions (NCLs) showed differences for MACE, MI, revascularization, and rehospitalization between the two groups. CONCLUSION The rates of MACE, MI, and revascularization are greater in DM than in non-DM patients in terms of all lesions, CLs, and NCLs. Except for CLs, the readmission rate is greater for unstable or progressive angina. Plaque characteristics are similar between patients with and without diabetes. Prospero registration number CRD42023474226.
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Affiliation(s)
- Yuchen Ma
- Department of Medical Informatics, Medical School of Nantong University, Nantong, 226001, China
| | - Huiying Gao
- Department of Medical Informatics, Medical School of Nantong University, Nantong, 226001, China
| | - Huiqun Wu
- Department of Medical Informatics, Medical School of Nantong University, Nantong, 226001, China.
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Cho S, Cho H, Min H, Lee JG, Kim TO, Lee PH, Lee SW, Kang SJ. Clinical impact of deep learning-derived intravascular ultrasound characteristics in patients with deferred coronary artery. Int J Cardiol 2024; 417:132543. [PMID: 39265789 DOI: 10.1016/j.ijcard.2024.132543] [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: 06/24/2024] [Revised: 08/23/2024] [Accepted: 09/09/2024] [Indexed: 09/14/2024]
Abstract
Prognostic markers for long-term outcomes are lacking in patients with deferred (nonculprit) coronary artery lesions. This study aimed to identify the morphological criteria for predicting adverse outcomes and validate their clinical impact. Using deep learning models, we extracted geometrical parameters and maximal attenuation (or calcium) burden index (ABI-max or CBI-max) from the intravascular ultrasound (IVUS) images of nonculprit vessels in 1115 patients. The endpoints included cardiac death, myocardial infarction, and target vessel revascularization of nonculprit vessel. Cardiac death occurred in 27 (2.4 %) patients at 3 years and 39 (3.5 %) patients at 5 years. At 5 years, the cardiac death-free survival rate was significantly lower with ABP-max ≥11.37 % vs. < 11.37 % (90.0 % vs. 98.7 %), CBI-max ≥13.40 % vs. < 13.40 % (92.8 % vs. 98.4 %), and percent atheroma volume ≥ 51.35 % vs. < 51.35 % (94.0 % vs. 97.7) (all log-rank p < 0.001). The independent predictors of 5-year cardiovascular mortality were age (hazard ratio [HR] 1.21), female sex (HR 0.33), history of heart failure (HR 6.06), chronic kidney disease (HR 18.28), ABI-max (HR 1.04), and CBI-max (HR 1.05). The independent determinants of 5-year target vessel revascularization of nonculprit vessel were fractional flow reserve (HR 0.95 per 0.01 increase), minimal lumen area (HR 0.63), and plaque burden (HR 1.15). In patients with nonculprit coronary artery lesions, a large burden of attenuated or calcified plaques predicted cardiac mortality, while IVUS geometry was associated with repeat revascularization. Thus, deep learning-based IVUS analysis of the whole target vessel may help clinicians identify high-risk lesions.
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Affiliation(s)
- Sungsoo Cho
- Division of Cardiology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyungjoo Cho
- Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Hyunseok Min
- Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - June-Goo Lee
- Biomedical Engineering Research Center, Asan Institute for Life Sciences, Seoul, Republic of Korea
| | - Tae Oh Kim
- Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Pil Hyung Lee
- Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung-Whan Lee
- Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Soo-Jin Kang
- Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
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35
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Gandhi A, Rajkumar R, Dakka SN, Sania J, Khurram F, Cabrera J, N L S. Mindfulness training for cardiovascular health in type 2 diabetes: A critical review. Curr Probl Cardiol 2024; 49:102833. [PMID: 39313043 DOI: 10.1016/j.cpcardiol.2024.102833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 09/03/2024] [Indexed: 09/25/2024]
Abstract
Mindfulness training has gained increasing attention as a potential intervention to improve cardiovascular health, particularly in populations with chronic conditions, such as type 2 diabetes. Given the heightened cardiovascular risk associated with type 2 diabetes, identifying effective non-pharmacological strategies to mitigate these risks is crucial. This critical review assessed the current evidence on the impact of mindfulness training on cardiovascular health in individuals with type 2 diabetes. A comprehensive literature search was conducted using the PubMed database, and studies were selected based on stringent inclusion and exclusion criteria. The search strategy was meticulously designed to filter out high-quality articles and ensure that only the most relevant and rigorous studies were included in the analysis. The findings from this review suggest that while mindfulness training has the potential to improve cardiovascular health in individuals with type 2 diabetes, evidence remains mixed. Some studies have reported significant improvements in cardiovascular markers, such as blood pressure and inflammation, while others have shown limited or no effects. This variability highlights the need for further research to better understand the mechanisms underlying these outcomes and identify the most effective mindfulness interventions for this population. In conclusion, mindfulness training appears to be a promising approach for enhancing cardiovascular health in Type 2 diabetes patients, yet the current evidence is inconclusive. Future research should focus on standardizing mindfulness interventions, conducting larger clinical trials, and exploring the long-term benefits of these interventions on cardiovascular outcomes in high-risk populations.
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Affiliation(s)
- Arnav Gandhi
- Rama Medical College Hospital and Research Centre, Hapur, Rama City, NH-9, Delhi Meerut Expressway, Near Mother Dairy, Pilkhuwa, Hapur (U.P.) 245304, India
| | - Rhenita Rajkumar
- Dnipro State Medical University, Volodymyra Vernadskoho St, 9, Dnipro, Dnipropetrovsk Oblast 49044Ukraine
| | - Sanjay Nehru Dakka
- Kurnool Medical College, Budhawarpet, Kisan Ghat Road, Kurnool 518002, India
| | - Jeba Sania
- Gauhati University, Jalukbari, Guwahati, Assam 781014, India.
| | - Fatima Khurram
- Federal Medical College Islamabad, G8/4 ICT, Islamabad, Pakistan
| | - Jorge Cabrera
- Universidad de Guayaquil - Escuela de Medicina, Delta Av. Guayaquil, Ecuador
| | - Swathi N L
- Jawaharlal Nehru Technological University, Anantapuram, Andhra Pradesh, India
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Zarei M, Sahebi Vaighan N, Farjoo MH, Talebi S, Zarei M. Incretin-based therapy: a new horizon in diabetes management. J Diabetes Metab Disord 2024; 23:1665-1686. [PMID: 39610543 PMCID: PMC11599551 DOI: 10.1007/s40200-024-01479-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 07/22/2024] [Indexed: 11/30/2024]
Abstract
Diabetes mellitus, a metabolic syndrome characterized by hyperglycemia and insulin dysfunction, often leads to serious complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease. Incretins, gut peptide hormones released post-nutrient intake, have shown promising therapeutic effects on these complications due to their wide-ranging biological impacts on various body systems. This review focuses on the role of incretin-based therapies, particularly Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, in managing diabetes and its complications. We also discuss the potential of novel agents like semaglutide, a recently approved oral compound, and dual/triple agonists targeting GLP-1/GIP, GLP-1/glucagon, and GLP-1/GIP/glucagon receptors, which are currently under investigation. The review aims to provide a comprehensive understanding of the beneficial impacts of natural incretins and the therapeutic potential of incretin-based therapies in diabetes management.
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Affiliation(s)
- Malek Zarei
- Department of Pharmacology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Navideh Sahebi Vaighan
- Department of Pharmacology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Hadi Farjoo
- Department of Pharmacology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soosan Talebi
- Department of Pharmacology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Zarei
- Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA USA
- John B. Little Center for Radiation Sciences, Harvard T.H Chan School of Public Health, Boston, MA USA
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Hawkins NM, Kaplan A, Ko DT, Penz E, Bhutani M. Is 'Cardiopulmonary' the New 'Cardiometabolic'? Making a Case for Systems Change in COPD. Pulm Ther 2024; 10:363-376. [PMID: 39249675 PMCID: PMC11573969 DOI: 10.1007/s41030-024-00270-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 08/20/2024] [Indexed: 09/10/2024] Open
Abstract
Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) have a syndemic relationship with shared risk factors and complex interplay between genetic, environmental, socioeconomic, and pathophysiological mechanisms. CVD is among the most common comorbidities in patients with COPD and vice versa. Patients with COPD, irrespective of their disease severity, are at increased risk of CVD morbidity and mortality, driven in part by COPD exacerbations. Despite these known interrelationships, CVD is underestimated and undertreated in patients with COPD. Similarly, COPD is an independent risk-enhancing factor for adverse cardiovascular (CV) events, yet it is not incorporated into current CV risk assessment tools, leading to under-recognition and undertreatment. There is a pressing need for systems change in COPD management to move beyond symptom control towards a comprehensive cardiopulmonary disease paradigm with proactive prevention of exacerbations and adverse cardiopulmonary outcomes and mortality. However, there is a dearth of evidence defining optimal cardiopulmonary care pathways. Fortunately, there is a precedent to support systems-level change in the field of diabetes, which evolved from glycemic control to comprehensive multi-organ risk assessment and management. Key elements included integrated multidisciplinary care, intensive risk factor management, coordination between primary and specialist care, care pathways and protocols, education and self management, and disease-modifying therapies. This commentary article draws parallels between the cardiometabolic and cardiopulmonary paradigms and makes a case for systems change towards multidisciplinary, integrated cardiopulmonary care, using the evolution in diabetes care as a potential framework.
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Affiliation(s)
- Nathaniel M Hawkins
- Centre for Cardiovascular Innovation, Division of Cardiology, University of British Columbia, 2775 Laurel Street, 9th Floor Room 9123, Vancouver, BC, V5Z 1M9, Canada.
| | - Alan Kaplan
- Family Physician Airways Group of Canada, University of Toronto, Toronto, ON, Canada
| | - Dennis T Ko
- Division of Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
| | - Erika Penz
- Division of Respirology, Critical Care and Sleep Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Mohit Bhutani
- Department of Medicine, University of Alberta, Edmonton, AB, Canada
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James TJ, Corbett J, Cummings M, Allard S, Bailey SJ, Eglin C, Belcher H, Piccolo DD, Tipton M, Perissiou M, Saynor ZL, Shepherd AI. The effect of repeated hot water immersion on vascular function, blood pressure and central haemodynamics in individuals with type 2 diabetes mellitus. J Therm Biol 2024; 126:104017. [PMID: 39642665 DOI: 10.1016/j.jtherbio.2024.104017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 11/16/2024] [Accepted: 11/19/2024] [Indexed: 12/09/2024]
Abstract
Type 2 diabetes mellitus (T2DM) is characterised by endothelial dysfunction, leading to increased risk of cardiovascular disease. Emerging evidence suggest that HWI may favourably improve vascular function but data are limited in individual with T2DM. The aim was to investigate whether repeated hot water immersion (HWI) improved macrovascular, microvascular and central haemodynamic function in individuals with T2DM. Fourteen individuals completed a pre-post experimental study where participants were assessed pre- and post-8-10 × 1 h HWI sessions (40 °C water) undertaken within a 14-day period. During HWIs, body position was adjusted to clamp rectal temperature at 38.5-39.0 °C for the duration of the immersion. Stroke volume index (SVi), cardiac index (Q˙ i), resting heart rate (HR), systolic blood pressure (SBP), diastolic BP (DBP), brachial flow-mediated dilation (FMD) and cutaneous microvascular endothelial function (via transdermal iontophoresis) and plasma [nitrate] and [nitrite] (NOX; via ozone chemiluminescence) were assessed pre- and post HWI. Neither brachial FMD measures of macrovascular endothelial function (p = 0.43) or forearm microvascular function (ACh max, p = 0.63; ACh area under curve (AUC), p = 0.63; insulin max, p = 0.51; insulin AUC, p = 0.86) or NOX (p = 0.38) were changed. Q˙ i (p < 0.01), SVi (p < 0.02) and resting HR (p < 0.01) were all significantly reduced following the 10-days HWI intervention. SBP was reduced (p = 0.03), whereas DBP was unchanged (p = 0.56). HWI may represent an appropriate intervention to improve Q˙ I, SVi and BP in individuals with T2DM, but not macrovascular endothelial or cutaneous microvascular function.
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Affiliation(s)
- Thomas J James
- School of Sport and Exercise Sciences, Faculty of Science, Liverpool John Moores University, Liverpool, UK
| | - Jo Corbett
- School of Psychology, Sport and Health Science, Faculty of Science and Health, University of Portsmouth, UK
| | - Michael Cummings
- Diabetes and Endocrinology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| | - Sharon Allard
- Diabetes and Endocrinology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| | - Stephen J Bailey
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
| | - Clare Eglin
- School of Psychology, Sport and Health Science, Faculty of Science and Health, University of Portsmouth, UK
| | - Harvey Belcher
- School of Psychology, Sport and Health Science, Faculty of Science and Health, University of Portsmouth, UK
| | - Daniel D Piccolo
- School of Psychology, Sport and Health Science, Faculty of Science and Health, University of Portsmouth, UK
| | - Michael Tipton
- School of Psychology, Sport and Health Science, Faculty of Science and Health, University of Portsmouth, UK
| | - Maria Perissiou
- School of Psychology, Sport and Health Science, Faculty of Science and Health, University of Portsmouth, UK
| | - Zoe L Saynor
- School of Psychology, Sport and Health Science, Faculty of Science and Health, University of Portsmouth, UK; School of Health Sciences, Faculty of Environmental and Life Sciences, University of Southampton, UK
| | - Anthony I Shepherd
- School of Psychology, Sport and Health Science, Faculty of Science and Health, University of Portsmouth, UK; Diabetes and Endocrinology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UK.
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Yu S, Zhao W, Qian B. Uncover visit-to-visit blood pressure variability as the hidden risk factor/predictor for coronary artery disease, stroke and malignant tumor in patients with type 2 diabetes. Heliyon 2024; 10:e40406. [PMID: 39641046 PMCID: PMC11617719 DOI: 10.1016/j.heliyon.2024.e40406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 09/19/2024] [Accepted: 11/13/2024] [Indexed: 12/07/2024] Open
Abstract
Visit-to-visit blood pressure variability is a factor for a series of cardiovascular diseases in hypertensive patients. Hypertension is a common complication of patients with type 2 diabetes mellitus. Our research demonstrated that blood pressure variability is more important than systolic blood pressure to be associated with the occurrence of coronary artery disease and stroke. However, the importance of visit-to-visit blood pressure variability was easily overlooked. The results aimed to inform the health professionals the significance of stability blood pressure variability in the blood pressure management for patients with type 2 diabetes.
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Affiliation(s)
- Shoukai Yu
- Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, China
| | - Wensui Zhao
- Shanghai Changning District Center for Disease Control and Prevention, NO. 39, Yunwushan Road, Changning District, Shanghai, 2000040, China
| | - Biyun Qian
- Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, China
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Xie H, Jiang MJ. Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiovascular Outcomes in Patients with Acute Coronary Syndrome and Type 2 Diabetes. Diabetes Metab Syndr Obes 2024; 17:4377-4386. [PMID: 39600926 PMCID: PMC11591705 DOI: 10.2147/dmso.s459368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 06/25/2024] [Indexed: 11/29/2024] Open
Abstract
Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with acute coronary syndrome (ACS) and type 2 diabetes (T2D). Methods The clinical data of 88 patients with ACS and T2D who were treated with SGLT2i between January 2020 and December 2021 were collected as the case group through convenience sampling. Patients taking other hypoglycaemic drugs were included as the control group in a 1:1 ratio matched with the case group using retrospective propensity score matching. Relevant data were subsequently collected from both groups for comparison. Results Statistically significant differences were observed in glycated haemoglobin (HbA1c) between the two groups (8.11[6.93, 9.41] vs 7.51[6.52, 9.14]%; Z=2.109; P=0.035). The SGLT2i group showed a decrease in major adverse cardiovascular events (MACEs) (P<0.001), secondary composite endpoint events (P=0.024), heart failure readmission (P=0.042) and unplanned revascularisation (P=0.014) compared with the control group. Moreover, the multivariate analysis showed that SGLT2i significantly reduced the risk of MACEs (hazard ratio [HR], 0.472; 95% CI, 0.321-0.694; P<0.001) and unplanned revascularisation (HR, 0.422; 95% CI, 0.212-0.842; P=0.014). In patients with reduced ejection fraction, SGLT2i significantly reduced the risk of MACEs (HR, 0.258; 95% CI, 0.106-0.626; P=0.003) compared with the control group. By contrast, in patients without reduced ejection fraction, SGLT2i significantly reduced the risk of MACEs (HR, 0.640; 95% CI, 0.412-0.996; P=0.048) and unplanned revascularisation (HR, 0.464; 95% CI, 0.222-0.969; P=0.041) compared with the control group. Conclusion In addition to significantly reducing the risk of adverse cardiovascular events and unplanned revascularisation in patients with ACS and T2D, the use of SGLT2i can reduce the risk of adverse cardiovascular events regardless of the presence of reduced ejection fraction.
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Affiliation(s)
- Han Xie
- Department of Cardiovascular Medicine, The Central Hospital of Wuhan, Wuhan, People’s Republic of China
- Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, People’s Republic of China
| | - Ming-Jian Jiang
- Department of Cardiovascular Medicine, Huangshi Aikang Hospital in Hubei Province, Wuhan, People’s Republic of China
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Naveed MA, Ali A, Neppala S, Ahmed F, Patel P, Azeem B, Rehan MO, Iqbal R, Mubeen M, Fath A, Paul T. Trends in coronary artery disease mortality among adults with diabetes: Insights from CDC WONDER (1999-2020). CARDIOVASCULAR REVASCULARIZATION MEDICINE 2024:S1553-8389(24)00716-4. [PMID: 39537466 DOI: 10.1016/j.carrev.2024.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 10/25/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Coronary artery disease (CAD) in diabetes mellitus (DM) is a significant cause of mortality among US adults. This study investigates trends in CAD-related mortality in adults aged 25 and older with DM, focusing on geographic, gender, and racial/ethnic disparities from 1999 to 2020. METHODS A retrospective analysis was conducted using death certificate data from the CDC WONDER database from 1999 to 2020. Age-adjusted mortality rates (AAMRs), annual percent change (APC), and average annual percentage change (AAPC) were calculated per 100,000 persons, stratified by year, sex, race/ethnicity, and geographical region. RESULTS CAD in DM accounted for 1,462,279 deaths among US adults aged 25+. Most deaths occurred in medical facilities (44.2 %) and at home (29.3 %). The overall AAMR for CAD in DM-related deaths decreased from 36.3 in 1999 to 31.7 in 2020, with an AAPC of -0.96 (95 % CI: -1.29 to -0.77, p < 0.000001). Men had higher AAMRs (41.6) compared to women (22.6), with a more significant decrease in women (AAPC: -2.10, p < 0.000001) than in men (AAPC: -0.34, p = 0.001200). Racial/ethnic disparities showed the highest AAMRs in American Indians/Alaska Natives (43.6), followed by Blacks (37.8), Hispanics (33.8), Whites (29.7), and Asians/Pacific Islanders (22.5). The most significant decrease was in Hispanics (AAPC: -1.64, p < 0.000001). Geographically, AAMRs ranged from 13.7 in Nevada to 51.3 in West Virginia, with the highest mortality observed in the Midwest (AAMR: 34.5). Nonmetropolitan areas exhibited higher AAMRs (35.2) than metropolitan areas (29.7), with a more pronounced decrease in metropolitan areas (AAPC: -1.22, p < 0.000001) compared to nonmetropolitan areas (AAPC: -0.03, p = 0.854629). CONCLUSION The notable increase in mortality rates associated with CAD among patients with DM from 2018 to 2020 presents a substantial concern that necessitates targeted public health interventions to ensure equitable access to cardiovascular care.
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Affiliation(s)
- Muhammad Abdullah Naveed
- Department of Cardiology, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Ahila Ali
- Department of Cardiology, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Sivaram Neppala
- Department of Cardiology, University of Texas Health Sciences Center, San Antonio, TX, USA.
| | - Faizan Ahmed
- Department of Internal Medicine, Ameeruddin Medical College, Lahore General Hospital, Lahore, Pakistan
| | - Palak Patel
- Department of Internal Medicine, New York Medical College at Saint Michael's Medical Center, Newark, NJ 07102, USA
| | - Bazil Azeem
- Department of Cardiology, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan
| | - Muhammad Omer Rehan
- Department of Cardiology, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Rabia Iqbal
- Department of Cardiology, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Manahil Mubeen
- Department of Cardiology, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Ayman Fath
- Department of Cardiology, University of Texas Health Sciences Center, San Antonio, TX, USA
| | - Timir Paul
- Department of Cardiovascular Sciences, Ascension St. Thomas Hospital/University of Tennessee Health Sciences Center, Nashville, TN, USA
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Hilser JR, Spencer NJ, Afshari K, Gilliland FD, Hu H, Deb A, Lusis AJ, Wilson Tang W, Hartiala JA, Hazen SL, Allayee H. COVID-19 Is a Coronary Artery Disease Risk Equivalent and Exhibits a Genetic Interaction With ABO Blood Type. Arterioscler Thromb Vasc Biol 2024; 44:2321-2333. [PMID: 39381876 PMCID: PMC11495539 DOI: 10.1161/atvbaha.124.321001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 08/08/2024] [Indexed: 10/10/2024]
Abstract
BACKGROUND COVID-19 is associated with acute risk of major adverse cardiac events (MACE), including myocardial infarction, stroke, and mortality (all-cause). However, the duration and underlying determinants of heightened risk of cardiovascular disease and MACE post-COVID-19 are not known. METHODS Data from the UK Biobank was used to identify COVID-19 cases (n=10 005) who were positive for polymerase chain reaction (PCR+)-based tests for SARS-CoV-2 infection (n=8062) or received hospital-based International Classification of Diseases version-10 (ICD-10) codes for COVID-19 (n=1943) between February 1, 2020 and December 31, 2020. Population controls (n=217 730) and propensity score-matched controls (n=38 860) were also drawn from the UK Biobank during the same period. Proportional hazard models were used to evaluate COVID-19 for association with long-term (>1000 days) risk of MACE and as a coronary artery disease risk equivalent. Additional analyses examined whether COVID-19 interacted with genetic determinants to affect the risk of MACE and its components. RESULTS The risk of MACE was elevated in COVID-19 cases at all levels of severity (HR, 2.09 [95% CI, 1.94-2.25]; P<0.0005) and to a greater extent in cases hospitalized for COVID-19 (HR, 3.85 [95% CI, 3.51-4.24]; P<0.0005). Hospitalization for COVID-19 represented a coronary artery disease risk equivalent since incident MACE risk among cases without history of cardiovascular disease was even higher than that observed in patients with cardiovascular disease without COVID-19 (HR, 1.21 [95% CI, 1.08-1.37]; P<0.005). A significant genetic interaction was observed between the ABO locus and hospitalization for COVID-19 (Pinteraction=0.01), with risk of thrombotic events being increased in subjects with non-O blood types (HR, 1.65 [95% CI, 1.29-2.09]; P=4.8×10-5) to a greater extent than subjects with blood type O (HR, 0.96 [95% CI, 0.66-1.39]; P=0.82). CONCLUSIONS Hospitalization for COVID-19 represents a coronary artery disease risk equivalent, with post-acute myocardial infarction and stroke risk particularly heightened in non-O blood types. These results may have important clinical implications and represent, to our knowledge, one of the first examples of a gene-pathogen exposure interaction for thrombotic events.
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Affiliation(s)
- James R. Hilser
- Department of Population and Public Health Sciences (J.R.H., N.J.S., K.A., F.D.G., H.H., J.A.H., H.A.), Keck School of Medicine, University of Southern California, Los Angeles
- Department of Biochemistry and Molecular Medicine (J.R.H., N.J.S., K.A., H.A.), Keck School of Medicine, University of Southern California, Los Angeles
| | - Neal J. Spencer
- Department of Population and Public Health Sciences (J.R.H., N.J.S., K.A., F.D.G., H.H., J.A.H., H.A.), Keck School of Medicine, University of Southern California, Los Angeles
- Department of Biochemistry and Molecular Medicine (J.R.H., N.J.S., K.A., H.A.), Keck School of Medicine, University of Southern California, Los Angeles
| | - Kimia Afshari
- Department of Population and Public Health Sciences (J.R.H., N.J.S., K.A., F.D.G., H.H., J.A.H., H.A.), Keck School of Medicine, University of Southern California, Los Angeles
- Department of Biochemistry and Molecular Medicine (J.R.H., N.J.S., K.A., H.A.), Keck School of Medicine, University of Southern California, Los Angeles
| | - Frank D. Gilliland
- Department of Population and Public Health Sciences (J.R.H., N.J.S., K.A., F.D.G., H.H., J.A.H., H.A.), Keck School of Medicine, University of Southern California, Los Angeles
| | - Howard Hu
- Department of Population and Public Health Sciences (J.R.H., N.J.S., K.A., F.D.G., H.H., J.A.H., H.A.), Keck School of Medicine, University of Southern California, Los Angeles
| | - Arjun Deb
- Department of Medicine (A.D., A.J.L.), Keck School of Medicine, University of Southern California, Los Angeles
| | - Aldons J. Lusis
- Department of Medicine (A.D., A.J.L.), Keck School of Medicine, University of Southern California, Los Angeles
- Department of Microbiology, Immunology, and Molecular Genetics (A.J.L.), David Geffen School of Medicine of UCLA, CA
- Department of Human Genetics (A.J.L.), David Geffen School of Medicine of UCLA, CA
| | - W.H. Wilson Tang
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute (W.H.W.T., S.L.H.), Cleveland Clinic, OH
- Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute (W.H.W.T., S.L.H.), Cleveland Clinic, OH
- Center for Microbiome and Human Health (W.H.W.T., S.L.H.), Cleveland Clinic, OH
| | - Jaana A. Hartiala
- Department of Population and Public Health Sciences (J.R.H., N.J.S., K.A., F.D.G., H.H., J.A.H., H.A.), Keck School of Medicine, University of Southern California, Los Angeles
| | - Stanley L. Hazen
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute (W.H.W.T., S.L.H.), Cleveland Clinic, OH
- Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute (W.H.W.T., S.L.H.), Cleveland Clinic, OH
- Center for Microbiome and Human Health (W.H.W.T., S.L.H.), Cleveland Clinic, OH
| | - Hooman Allayee
- Department of Population and Public Health Sciences (J.R.H., N.J.S., K.A., F.D.G., H.H., J.A.H., H.A.), Keck School of Medicine, University of Southern California, Los Angeles
- Department of Biochemistry and Molecular Medicine (J.R.H., N.J.S., K.A., H.A.), Keck School of Medicine, University of Southern California, Los Angeles
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Ansari P, Khan JT, Chowdhury S, Reberio AD, Kumar S, Seidel V, Abdel-Wahab YHA, Flatt PR. Plant-Based Diets and Phytochemicals in the Management of Diabetes Mellitus and Prevention of Its Complications: A Review. Nutrients 2024; 16:3709. [PMID: 39519546 PMCID: PMC11547802 DOI: 10.3390/nu16213709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 09/27/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
Diabetes mellitus (DM) is currently regarded as a global public health crisis for which lifelong treatment with conventional drugs presents limitations in terms of side effects, accessibility, and cost. Type 2 diabetes (T2DM), usually associated with obesity, is characterized by elevated blood glucose levels, hyperlipidemia, chronic inflammation, impaired β-cell function, and insulin resistance. If left untreated or when poorly controlled, DM increases the risk of vascular complications such as hypertension, nephropathy, neuropathy, and retinopathy, which can be severely debilitating or life-threatening. Plant-based foods represent a promising natural approach for the management of T2DM due to the vast array of phytochemicals they contain. Numerous epidemiological studies have highlighted the importance of a diet rich in plant-based foods (vegetables, fruits, spices, and condiments) in the prevention and management of DM. Unlike conventional medications, such natural products are widely accessible, affordable, and generally free from adverse effects. Integrating plant-derived foods into the daily diet not only helps control the hyperglycemia observed in DM but also supports weight management in obese individuals and has broad health benefits. In this review, we provide an overview of the pathogenesis and current therapeutic management of DM, with a particular focus on the promising potential of plant-based foods.
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Affiliation(s)
- Prawej Ansari
- Comprehensive Diabetes Center, Heersink School of Medicine, University of Alabama, Birmingham (UAB), Birmingham, AL 35233, USA
- School of Pharmacy and Public Health, Department of Pharmacy, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
- Centre for Diabetes Research, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK; (Y.H.A.A.-W.); (P.R.F.)
| | - Joyeeta T. Khan
- School of Pharmacy and Public Health, Department of Pharmacy, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR 72205, USA
| | - Suraiya Chowdhury
- School of Pharmacy and Public Health, Department of Pharmacy, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
| | - Alexa D. Reberio
- School of Pharmacy and Public Health, Department of Pharmacy, Independent University, Bangladesh (IUB), Dhaka 1229, Bangladesh
| | - Sandeep Kumar
- Comprehensive Diabetes Center, Heersink School of Medicine, University of Alabama, Birmingham (UAB), Birmingham, AL 35233, USA
| | - Veronique Seidel
- Natural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK;
| | - Yasser H. A. Abdel-Wahab
- Centre for Diabetes Research, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK; (Y.H.A.A.-W.); (P.R.F.)
| | - Peter R. Flatt
- Centre for Diabetes Research, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK; (Y.H.A.A.-W.); (P.R.F.)
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Saedi S, Tan Y, Watson SE, Wintergerst KA, Cai L. Potential pathogenic roles of ferroptosis and cuproptosis in cadmium-induced or exacerbated cardiovascular complications in individuals with diabetes. Front Endocrinol (Lausanne) 2024; 15:1461171. [PMID: 39415790 PMCID: PMC11479913 DOI: 10.3389/fendo.2024.1461171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 09/16/2024] [Indexed: 10/19/2024] Open
Abstract
Diabetes and its complications are major diseases that affect human health. Diabetic cardiovascular complications such as cardiovascular diseases (CVDs) are the major complications of diabetes, which are associated with the loss of cardiovascular cells. Pathogenically the role of ferroptosis, an iron-dependent cell death, and cuproptosis, a copper-dependent cell death has recently been receiving attention for the pathogenesis of diabetes and its cardiovascular complications. How exposure to environmental metals affects these two metal-dependent cell deaths in cardiovascular pathogenesis under diabetic and nondiabetic conditions remains largely unknown. As an omnipresent environmental metal, cadmium exposure can cause oxidative stress in the diabetic cardiomyocytes, leading to iron accumulation, glutathione depletion, lipid peroxidation, and finally exacerbate ferroptosis and disrupt the cardiac. Moreover, cadmium-induced hyperglycemia can enhance the circulation of advanced glycation end products (AGEs). Excessive AGEs in diabetes promote the upregulation of copper importer solute carrier family 31 member 1 through activating transcription factor 3/transcription factor PU.1, thereby increasing intracellular Cu+ accumulation in cardiomyocytes and disturbing Cu+ homeostasis, leading to a decline of Fe-S cluster protein and reactive oxygen species accumulation in cardiomyocytes mitochondria. In this review, we summarize the available evidence and the most recent advances exploring the underlying mechanisms of ferroptosis and cuproptosis in CVDs and diabetic cardiovascular complications, to provide critical perspectives on the potential pathogenic roles of ferroptosis and cuproptosis in cadmium-induced or exacerbated cardiovascular complications in diabetic individuals.
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Affiliation(s)
- Saman Saedi
- Department of Animal Science, College of Agriculture, Shiraz University, Shiraz, Iran
| | - Yi Tan
- Pediatric Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, United States
- Wendy Novak Diabetes Institute, Norton Children’s Hospital, Louisville, KY, United States
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, United States
| | - Sara E. Watson
- Pediatric Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, United States
- Wendy Novak Diabetes Institute, Norton Children’s Hospital, Louisville, KY, United States
- Division of Endocrinology, Department of Pediatrics, University of Louisville, Norton Children’s Hospital, Louisville, KY, United States
| | - Kupper A. Wintergerst
- Pediatric Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, United States
- Wendy Novak Diabetes Institute, Norton Children’s Hospital, Louisville, KY, United States
- Division of Endocrinology, Department of Pediatrics, University of Louisville, Norton Children’s Hospital, Louisville, KY, United States
- The Center for Integrative Environmental Health Sciences, University of Louisville School of Medicine, Louisville, KY, United States
| | - Lu Cai
- Pediatric Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, United States
- Wendy Novak Diabetes Institute, Norton Children’s Hospital, Louisville, KY, United States
- Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, United States
- The Center for Integrative Environmental Health Sciences, University of Louisville School of Medicine, Louisville, KY, United States
- Department of Radiation Oncology, University of Louisville School of Medicine, Louisville, KY, United States
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Bignotto M, Bianco E, Centofanti L, Russo A, Dei Cas M, Zermiani P, Morano C, Samartin F, Bertolini E, Bifari F, Berra C, Zuin M, Paroni R, Battezzati PM, Folli F. Synergistic effects of glucose tolerance and BMI on cardiovascular events and all-cause mortality in a healthy population: CA.ME.LI.A study 7 years follow-up. Am J Physiol Endocrinol Metab 2024; 327:E498-E511. [PMID: 39196799 PMCID: PMC11482241 DOI: 10.1152/ajpendo.00181.2024] [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: 05/16/2024] [Revised: 08/08/2024] [Accepted: 08/20/2024] [Indexed: 08/30/2024]
Abstract
The CA.ME.LI.A (CArdiovascular risks, MEtabolic syndrome, LIver and Autoimmune disease) epidemiological study was conducted in Abbiategrasso (Milan, Italy) to identify risk factors for metabolic and cardiovascular disease in an apparently healthy population of northern Italy. The population (n = 2,545, 1,251 men, 1,254 women) was stratified according to body mass index [normal body weight (NBW): <25 kg/m2; overweight-obese (OWO): ≥25 kg/m2] and according to fasting blood glucose [normal fasting glucose: <100 mg/dL; impaired fasting glucose (IFG): 100-125 mg/dL; diabetes mellitus (DM): ≥126 mg/dL]. The incidence of cardiovascular (CV) events and overall mortality were studied by the Kaplan-Meier method using the log rank test. Univariate analysis was conducted with time-dependent Cox models. During the 7-yr follow-up period, 80 deaths and 149 CV events occurred. IFG [hazard ratio (HR): 2.81; confidence interval (CI): 1.37-5.77; P = 0.005], DM (HR: 4.88; CI: 1.47-16; P = 0.010), or OWO (HR: 2.78; CI:1.68-4.59; P < 0.001) all produced significant increases in CV events and deaths. In the combination IFG/OWO (HR: 5.51; CI: 3.34-9.08; P < 0.001), there was an apparent additive effect of the two conditions, whereas in the combination DM/OWO (HR: 12.71; CI: 7.48-22; P < 0.001), there was an apparent multiplicative effect on the risk for CV events and deaths. In males, the DM/NBW group had a higher incidence of cardiovascular events and deaths than the IFG/OWO group. In contrast, in females, the IFG/OWO group had a higher incidence of cardiovascular events and deaths than the DM/NBW group. In women, there was a greater incidence of CV events in the IFG/OWO group (HR: 6.23; CI: 2.88-13; P < 0.001) than in men in the same group (HR: 4.27; CI: 2.15-8.47; P < 0.001). Consistent with these data, also all-cause mortality was progressively increased by IFG/DM and OWO, with an apparently exponential effect in the combination DM/OWO (HR: 11.78; CI: 6.11-23; P < 0.001). IFG/DM and OWO, alone or in combination, had major effects in increasing mortality for all causes and CV events. The relative contributions of hyperglycemia and overweight/obesity on cardiovascular events and deaths were apparently, to a certain extent, sex dependent. Females were more affected by overweight/obesity either alone or combined with IFG, as compared with males.NEW & NOTEWORTHY For the first time, the combined effects of glucose tolerance and BMI have been investigated in an apparently healthy large population sample of a city in the north of Italy. We found that there are synergistic effects of glucose levels with BMI to increase not only cardiovascular events and deaths but also cancer-related deaths and all-cause mortality.
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Affiliation(s)
- Monica Bignotto
- Liver and Gastroenterology Unit, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Elena Bianco
- Liver and Gastroenterology Unit, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
- Medicine and Liver Unit, ASST Santi Paolo e Carlo, Milan, Italy
| | - Lucia Centofanti
- Clinical Biochemistry and Mass Spectrometry Unit, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Antonio Russo
- Epidemiology Unit, Agency for Health Protection of the Metropolitan City of Milan, Milan, Italy
| | - Michele Dei Cas
- Clinical Biochemistry and Mass Spectrometry Unit, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Paola Zermiani
- Liver and Gastroenterology Unit, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Camillo Morano
- Clinical Biochemistry and Mass Spectrometry Unit, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Federica Samartin
- Liver and Gastroenterology Unit, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
- Medicine and Liver Unit, ASST Santi Paolo e Carlo, Milan, Italy
| | | | - Francesco Bifari
- Laboratory of Cell Metabolism and Regenerative Medicine, Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, LITA, Segrate, Italy
| | - Cesare Berra
- Dipartimento Endocrino-Metabolico, IRCCS MultiMedica, Milano, Italy
| | - Massimo Zuin
- Liver and Gastroenterology Unit, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Rita Paroni
- Clinical Biochemistry and Mass Spectrometry Unit, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Pier Maria Battezzati
- Liver and Gastroenterology Unit, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
- Medicine and Liver Unit, ASST Santi Paolo e Carlo, Milan, Italy
| | - Franco Folli
- Departmental Unit for Diabetes and Metabolic Diseases, ASST Santi Paolo e Carlo, Milan, Italy
- Departmental Unit for Diabetes and Metabolic Diseases, ASST Santi Paolo e Carlo, Milan, Italy
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Sakamoto T, Miyamoto H, Hashizume J, Akamatsu H, Akagi T, Kodama Y, Hamano H, Zamami Y, Ohyama K. Differences in the Adverse Event Profiles of Sodium-Glucose Cotransporter 2 Inhibitors used in Patients with Diabetes Mellitus and Heart Failure: An Analysis Using the Japanese Adverse Drug Event Report Database. Clin Drug Investig 2024; 44:761-771. [PMID: 39402407 DOI: 10.1007/s40261-024-01394-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/09/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND AND OBJECTIVES Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently become a standard treatment for heart failure and renal failure. The number of patients using these drugs is expected to increase further. However, no adverse drug event profiles have been published for the use of SGLT2i in patients without diabetes. To analyze and clarify the differences in adverse event profiles associated with the use of SGLT2i in patients with diabetes or heart failure using the Japanese Adverse Drug Event Report (JADER) database, a Japanese reporting system for adverse events. METHODS The JADER database, containing reports submitted between April 2004 and January 2024, was used. Our study focused on patients with diabetes or heart failure, analyzing adverse events associated with empagliflozin and dapagliflozin. The reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated for signal detection. RESULTS We identified risks of adverse drug events such as ketoacidosis, urinary tract infection, dehydration, and acidosis in both patient groups. However, the risks of cerebral infarction and ischemic heart disease were identified only in patients with diabetes, while risks of renal dysfunction, hypoglycemia, and sepsis were identified only in those with heart failure. CONCLUSION Adverse events should be managed appropriately for patients using SGLT2i, as the adverse event profiles differ between those with diabetes and those with heart failure. Understanding these differences is crucial for improving patient safety and optimizing treatment outcomes.
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Affiliation(s)
- Toshiaki Sakamoto
- Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki Prefecture, 852-8501, Japan.
| | - Hirotaka Miyamoto
- Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
| | - Junya Hashizume
- Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki Prefecture, 852-8501, Japan
| | - Hayato Akamatsu
- Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki Prefecture, 852-8501, Japan
| | - Tomoaki Akagi
- Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki Prefecture, 852-8501, Japan
| | - Yukinobu Kodama
- Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki Prefecture, 852-8501, Japan
| | - Hirofumi Hamano
- Department of Pharmacy, Okayama University Hospital, Okayama, Japan
| | - Yoshito Zamami
- Department of Pharmacy, Okayama University Hospital, Okayama, Japan
| | - Kaname Ohyama
- Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki Prefecture, 852-8501, Japan
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Sugur K, Kempegowda SN, Shambu SK, Mahadevappa M, Kengegowda VK, Gowda J, Thimmulappa RK. Serum lipid peroxidation potential as a biomarker for risk-stratification of coronary artery disease in patients with type 2 diabetes mellitus. Diabetes Metab Syndr 2024; 18:103143. [PMID: 39481297 DOI: 10.1016/j.dsx.2024.103143] [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: 09/29/2023] [Revised: 10/22/2024] [Accepted: 10/28/2024] [Indexed: 11/02/2024]
Abstract
AIM We examined the serum lipid peroxidation potential as an estimate of systemic oxidative stress levels in people with type 2 diabetes (T2D) for coronary artery disease (CAD) risk stratification. METHODS We prospectively recruited patients and categorized them into four subgroups based on diabetes and severity of CAD [Gensini score <20, non-significant CAD; Gensini score >20, significant CAD]: non-diabetics with non-significant CAD, diabetics with non-significant CAD, non-diabetics with significant CAD and diabetics with significant CAD. Lipid profile, HbA1c, fasting blood glucose, and oxidized LDL were assessed. A newly developed assay estimated serum lipid peroxidation potential. RESULTS Circulatory oxidized LDL levels were significantly higher in patients with severe CAD compared to non-diabetics with non-significant CAD, however no significant differences were observed across the four subgroups. Diabetics with non-significant CAD demonstrated significantly elevated serum lipid peroxidation potential compared to non-diabetics with non-significant CAD. Intriguingly, serum lipid peroxidation potential was markedly elevated in diabetics with non-significant CAD compared to both diabetics and non-diabetics with significant CAD. Poor glycemic control and reduced blood total antioxidant capacity were the primary factors contributing to increased serum lipid peroxidation potential in diabetics with non-significant CAD group. CONCLUSIONS We found that people with T2D who are associated with non-significant CAD are more vulnerable to oxidative stress than those with significant CAD. The study demonstrates the application of 'serum lipid peroxidation potential' assay for risk-stratification of CAD in people with T2D.
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Affiliation(s)
- Kavya Sugur
- Department of Biochemistry, Centre of Excellence in Molecular Biology & Regenerative Medicine, India
| | - Swetha N Kempegowda
- Department of Biochemistry, Centre of Excellence in Molecular Biology & Regenerative Medicine, India
| | - Sunil K Shambu
- Department of Cardiology, JSS Medical College, JSS Academy of Higher Education & Research, Mysore, Karnataka, 570015, India
| | - Manjappa Mahadevappa
- Department of Cardiology, JSS Medical College, JSS Academy of Higher Education & Research, Mysore, Karnataka, 570015, India
| | - Vinay K Kengegowda
- Department of Cardiology, JSS Medical College, JSS Academy of Higher Education & Research, Mysore, Karnataka, 570015, India
| | - Jadeppa Gowda
- Department of Biochemistry, Centre of Excellence in Molecular Biology & Regenerative Medicine, India
| | - Rajesh K Thimmulappa
- Department of Biochemistry, Centre of Excellence in Molecular Biology & Regenerative Medicine, India.
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48
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Birindwa G, Maeng M, Thrane PG, Gyldenkerne C, Thomsen RW, Olesen KKW. Causes of Excess Mortality in Diabetes Patients Without Coronary Artery Disease: A Cohort Study Revealing Endocrinologic Contributions. Clin Epidemiol 2024; 16:571-585. [PMID: 39247670 PMCID: PMC11380490 DOI: 10.2147/clep.s463363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 07/23/2024] [Indexed: 09/10/2024] Open
Abstract
Background Diabetes mellitus (DM) patients without coronary artery disease (CAD) have a higher all-cause mortality rate than patients with neither DM nor CAD. We examined cause-specific death of DM patients with and without CAD. Methods We conducted a cohort study of all patients who underwent CAG in Western Denmark between 2003 and 2016. Using Danish health registries, patients were followed for a maximum of 10 years and stratified according to their DM and CAD status. Outcomes included all-cause-, cancer-, circulatory-, and endocrinologic death. Ten-year cumulative risks were computed as well as adjusted and unadjusted hazard ratios (aHR and HR). Results A total of 132,432 patients (28,524 deaths, median follow-up of 6.2 years) were included. Compared to patients with neither DM nor CAD, DM patients without CAD had a higher 10-year risk of all-cause death (27.9% versus 19.7%, aHR 1.43 [95% CI 1.35-1.52]), cancer death (7.2% versus 5.4%, aHR 1.29 [95% CI 1.15-1.46]), circulatory death (9.1% versus 6.9%, aHR 1.35 [95% CI 1.22-1.49]), and endocrinologic death (3.9% versus 0.3%, aHR 14.02 [95% CI 10.95-17.95]). Among endocrinologic deaths, 87% were due to classical complications of DM, such as diabetic nephropathy and ketoacidosis, in DM patients without CAD. Conclusion Diabetes patients without CAD exhibit a higher risk of all-cause mortality, driven primarily by elevated rates of cancer, circulatory, and endocrinologic deaths, particularly related to diabetic microvascular complications.
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Affiliation(s)
- Guilian Birindwa
- Department of Cardiology Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark
| | - Michael Maeng
- Department of Cardiology Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Department of Cardiology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark
| | | | - Christine Gyldenkerne
- Department of Cardiology Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark
| | - Reimar Wernich Thomsen
- Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark
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Huenges K, Rainer-Schmidt N, Panholzer B, Caliebe A, Hüttmann L, Kolat P, Thiem A, Attmann T, Fraund-Cremer S, Haneya A, Cremer J, Grothusen C. Impact of Diabetes in Patients With Acute Myocardial Infarction Undergoing Coronary Artery Bypass Surgery Within 48 Hours. Heart Lung Circ 2024; 33:1272-1279. [PMID: 38811293 DOI: 10.1016/j.hlc.2024.02.014] [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: 06/25/2023] [Revised: 02/10/2024] [Accepted: 02/13/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND Diabetic patients with coronary artery disease may benefit from elective coronary artery bypass graft (CABG) surgery. It is unknown whether this merit is transferable to patients with acute myocardial infarction (AMI) undergoing surgery. METHOD A total of 1,427 patients underwent CABG within 48 hours of being diagnosed with AMI at the current institution between 2001 and 2019. Of these patients, 206 (14.4%) had insulin-dependent diabetes mellitus (IDDM) and 148 (10.4%) had non-insulin dependent diabetes mellitus (NIDDM). Retrospective data analysis was performed. RESULTS Patients with NIDDM showed the highest perioperative risk profile, with a EuroScore II of 11.6 (±10.3) compared with 7.8 (±8.0) in non-diabetic patients and 8.4 (±7.8) in patients with IDDM (p<0.001). Sub-analysis demonstrated a higher proportion of non-ST-elevation myocardial infarction patients in the NIDDM cohort compared with the IDDM cohort (70.9% vs 56.8%; p=0.005). Postoperatively, NIDDM patients had more sepsis (p<0.01) and longer ventilation times (p<0.001) compared with non-DM and IDDM patients (p<0.01). Wound healing complications were rare, but almost twice as high in NIDDM patients compared with non-DM and IDDM patients (4.7% vs 0.9% vs 2.4%, respectively). The 30-day mortality was highest in the NIDDM cohort (18.3% vs 11.3% vs 7.8%; p=0.012). Analysis of survival for up to 15 years revealed a significantly reduced survival of diabetic patients compared with non-diabetic patients, with lowest survival rates in NIDDM patients (p<0.001). CONCLUSIONS Non-insulin dependent diabetes mellitus patients undergoing CABG within 48 hours of being diagnosed with AMI are at increased risk of short-term and long-term complications. Therefore, this particular group should undergo a careful evaluation concerning the expected risks and benefits of CABG in this setting.
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Affiliation(s)
- Katharina Huenges
- Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Nele Rainer-Schmidt
- Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Bernd Panholzer
- Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Amke Caliebe
- Institut für Medizinische Informatik und Statistik, Christian-Albrechts-Universität zu Kiel and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Lennart Hüttmann
- Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Philipp Kolat
- Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Alexander Thiem
- Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Tim Attmann
- Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Sandra Fraund-Cremer
- Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Assad Haneya
- Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Jochen Cremer
- Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Christina Grothusen
- Department of Cardiovascular Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; Medizinische Klinik I, St. Johannes Hospital Dortmund, Dortmund, Germany.
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50
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Soroush N, Nekouei Shahraki M, Mohammadi Jouabadi S, Amiri M, Aribas E, Stricker BH, Ahmadizar F. Statin therapy and cardiovascular protection in type 2 diabetes: The role of baseline LDL-Cholesterol levels. A systematic review and meta-analysis of observational studies. Nutr Metab Cardiovasc Dis 2024; 34:2021-2033. [PMID: 38866619 DOI: 10.1016/j.numecd.2024.04.015] [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: 09/05/2023] [Revised: 04/12/2024] [Accepted: 04/24/2024] [Indexed: 06/14/2024]
Abstract
AIM The guidelines recommend statins to prevent cardiovascular events in patients with type 2 diabetes (T2D) however, the importance of baseline LDL-Cholesterol (LDL-C) levels remains controversial. This study aimed to determine the association of statin use in T2D patients with major adverse cardiovascular events (MACE) and all-cause mortality and whether this association differs by baseline LDL-C levels. DATA SYNTHESIS Medline, Embase, and Web of Science were systematically searched from inception until January 2022. Observational studies in patients with T2D comparing statin users vs non-users, with reports of the baseline LDL-C levels, were included. Random-effects meta-analysis and meta-regression were performed to estimate the overall effect on the risk of all-cause mortality and MACE (a composite of myocardial infarction, heart failure, stroke, and revascularization events) and the modification in the association by baseline LDL-C levels. We categorized studies according to their baseline LDL-C levels into 1) <100 mg/dl (2.59 mmol/l), 2) 100-130 mg/dl (2.59-3.37 mmol/l) and 3) >130 mg/dl (3.37 mmol/l) categories. A total of 9 cohort studies (n = 403,411 individuals) fulfilled our criteria. The follow-up duration ranged from 1.7 to 8 years. The overall combined estimate showed that statin therapy was associated with a significantly lower risk of MACE (Hazard Ratio (HR): 0.70 [95% CI 0.59 to 0.83], Absolute risk reduction percentage (ARR%): 3.19% [95%CI 0.88 to 5.50%) and all-cause mortality (HR: 0.60 [95% CI 0.46 to 0.79], ARR%: 5.23% [95% CI 2.18 to 8.28%), but varied, albeit not statistically significant, by baseline LDL-C levels. Studies with baseline LDL-C levels higher than 130 mg/dl had the greatest reduction of MACE (HR: 0.58 [95% CI 0.37 to 0.90]) and all-cause mortality risk (HR: 0.51 [95% CI [ 0.29 to 0.90]). The HRs of MACE in studies with LDL-C levels of 100-130 mg/dl and <100 mg/dl categories were respectively (0.70 [95% CI 0.59 to 0.83]) and (0.83 [95% CI [0.68 to 1.00]); and that of all-cause mortality were respectively (0.62 [95% CI 0.38 to 1.01]) and (0.67 [95% CI [0.44 to 1.02]). Statin use changes the HRs of MACE (0.99 [95%CI, 0.98 to 0.99]; P = 0.04) and all-cause mortality (0.99 [95% CI 0.98 to 1.01]; P = 0.8) per each mg/dl increase in baseline LDL-C level in meta-regression analyses. CONCLUSION Statin therapy in patients with T2D was associated with reduced risk of MACE and all-cause mortality. Significant differences across studies with different baseline LDL-C levels were not observed.
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Affiliation(s)
- Negin Soroush
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Mitra Nekouei Shahraki
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Soroush Mohammadi Jouabadi
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Pharmacology and Vascular Medicine Center, Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Masoud Amiri
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Elif Aribas
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Bruno H Stricker
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Fariba Ahmadizar
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Department of Data Science and Biostatistics, Julius Global Health, University Medical Center Utrecht, Utrecht, the Netherlands.
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