{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:36:14Z","timestamp":1792028174007,"version":"4.4.0"},"reference-count":119,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T00:00:00Z","timestamp":1622246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>In patients with diabetes, metabolic disorders disturb the physiological balance of coagulation and fibrinolysis, leading to a prothrombotic state characterized by platelet hypersensitivity, coagulation disorders and hypofibrinolysis. Hyperglycemia and insulin resistance cause changes in platelet number and activation, as well as qualitative and\/or quantitative modifications of coagulatory and fibrinolytic factors, resulting in the formation of fibrinolysis-resistant clots in patients with diabetes. Other coexisting factors like hypoglycemia, obesity and dyslipidemia also contribute to coagulation disorders in patients with diabetes. Management of the prothrombotic state includes antiplatelet and anticoagulation therapies for diabetes patients with either a history of cardiovascular disease or prone to a higher risk of thrombus generation, but current guidelines lack recommendations on the optimal antithrombotic treatment for these patients. Metabolic optimizations like glucose control, lipid-lowering, and weight loss also improve coagulation disorders of diabetes patients. Intriguing, glucose-lowering drugs, especially cardiovascular beneficial agents, such as glucagon-like peptide-1 receptor agonists and sodium glucose co-transporter inhibitors, have been shown to exert direct anticoagulation effects in patients with diabetes. This review focuses on the most recent progress in the development and management of diabetes related prothrombotic state.<\/jats:p>","DOI":"10.3390\/jcm10112419","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T01:51:37Z","timestamp":1622425897000},"page":"2419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":173,"title":["Effects of Hyperglycemia and Diabetes Mellitus on Coagulation and Hemostasis"],"prefix":"10.3390","volume":"10","author":[{"given":"Xiaoling","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1111-9042","authenticated-orcid":false,"given":"Nina C.","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9036-3723","authenticated-orcid":false,"given":"Danny M.","family":"Cohn","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus W.","family":"Hollmann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Hans","family":"DeVries","sequence":"additional","affiliation":[{"name":"Department of International Medicine, Amsterdam UMC location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2239-1260","authenticated-orcid":false,"given":"Jeroen","family":"Hermanides","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4412-9183","authenticated-orcid":false,"given":"Benedikt","family":"Preckel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Amsterdam UMC Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hulst, A.H., Visscher, M.J., Cherpanath, T.G.V., van de Wouw, L., Godfried, M.B., Thiel, B., Gerritse, B.M., Scohy, T.V., Bouwman, R.A., and Willemsen, M.G. (2020). Effects of Liraglutide on Myocardial Function After Cardiac Surgery: A Secondary Analysis of the Randomised Controlled GLOBE Trial. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030673"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.jtcvs.2011.03.009","article-title":"Investigators of the Multicenter Study of Perioperative Ischemia Research Group. Impact of hyperglycemia on perioperative mortality after coronary artery bypass graft surgery","volume":"142","author":"Szekely","year":"2011","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1152\/physrev.00016.2011","article-title":"New fundamentals in hemostasis","volume":"93","author":"Versteeg","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.blre.2014.09.003","article-title":"Fibrinolysis and the control of blood coagulation","volume":"29","author":"Chapin","year":"2015","journal-title":"Blood Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1042\/CS20160391","article-title":"Thrombosis in diabetes: A shear flow effect?","volume":"131","author":"Westein","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.amjcard.2019.11.030","article-title":"Endothelial Dysfunction, Fibrinolytic Activity, and Coagulation Activity in Patients with Atrial Fibrillation According to Type II Diabetes Mellitus Status","volume":"125","author":"Patti","year":"2020","journal-title":"Am. J. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s11886-019-1168-y","article-title":"Role of and Recent Evidence for Antiplatelet Therapy in Prevention of Cardiovascular Disease in Diabetes","volume":"21","author":"Sharma","year":"2019","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1111\/j.1538-7836.2010.03910.x","article-title":"Hyperglycemia: A prothrombotic factor?","volume":"8","author":"Lemkes","year":"2010","journal-title":"J. Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10555-017-9677-x","article-title":"Normal platelet function","volume":"36","author":"Holinstat","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_11","first-page":"77","article-title":"Effect of rapid desensitization on platelet inhibition and basophil activation in patients with aspirin hypersensitivity and coronary disease","volume":"3","author":"Neukirch","year":"2017","journal-title":"Eur. Heart J. Cardiovasc. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.prostaglandins.2015.05.002","article-title":"Platelets and diabetes mellitus","volume":"120","author":"Santilli","year":"2015","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_13","first-page":"26","article-title":"Study of Impact of Glycemic Status (HbA1c) on Platelet Activity measured by Mean Platelet Volume & Vascular Complications in Diabetics","volume":"67","author":"Saluja","year":"2019","journal-title":"J. Assoc. Physicians India"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Malachowska, B., Tomasik, B., Szadkowska, A., Baranowska-Jazwiecka, A., Wegner, O., Mlynarski, W., and Fendler, W. (2015). Altered platelets\u2019 morphological parameters in children with type 1 diabetes\u2014A case-control study. BMC Endocr. Disord., 15.","DOI":"10.1186\/s12902-015-0011-8"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.jdiacomp.2018.06.008","article-title":"Changes in platelet morphology indices in relation to duration of disease and glycemic control in children with type 1 diabetes mellitus","volume":"32","author":"Venkatesh","year":"2018","journal-title":"J. Diabetes Complicat."},{"key":"ref_16","first-page":"2292","article-title":"Investigation of mean platelet volume in patients with type 2 diabetes mellitus and in subjects with impaired fasting glucose: A cost-effective tool in primary health care?","volume":"7","author":"Ozder","year":"2014","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.numecd.2017.06.016","article-title":"Platelet indices and glucose control in type 1 and type 2 diabetes mellitus: A case-control study","volume":"27","author":"Zaccardi","year":"2017","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12933-018-0763-3","article-title":"Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: Molecular insights and therapeutic strategies","volume":"17","author":"Kaur","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"781857","DOI":"10.1155\/2014\/781857","article-title":"Overview of platelet physiology: Its hemostatic and nonhemostatic role in disease pathogenesis","volume":"2014","author":"Ghoshal","year":"2014","journal-title":"Sci. World J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12933-021-01267-w","article-title":"PAR-4\/Ca(2+)-calpain pathway activation stimulates platelet-derived microparticles in hyperglycemic type 2 diabetes","volume":"20","author":"Giannella","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1097\/MBC.0000000000000618","article-title":"Involvement of hyperglycemia in the development of platelet procoagulant response: The role of aldose reductase and platelet swelling","volume":"28","author":"Rusak","year":"2017","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s00540-018-2507-7","article-title":"Endothelium-dependent vasodilation in the cerebral arterioles of rats deteriorates during acute hyperglycemia and then is restored by reducing the glucose level","volume":"32","author":"Kito","year":"2018","journal-title":"J. Anesth."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"97","DOI":"10.2337\/diaclin.33.2.97","article-title":"Standards of medical care in diabetes-2015 abridged for primary care providers","volume":"33","year":"2015","journal-title":"Clin. Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"112","DOI":"10.4103\/0974-2727.163134","article-title":"Relationship Between Insulin Resistance and Mean Platelet Volume in Gestational Diabetes Mellitus","volume":"7","author":"Baldane","year":"2015","journal-title":"J. Lab. Physicians"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6370","DOI":"10.1038\/s41598-019-42783-w","article-title":"Retention of beneficial molecules and coagulation factors during haemodialysis and haemodiafiltration","volume":"9","author":"Voigt","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1038\/s41588-019-0470-3","article-title":"CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation","volume":"51","author":"Esteghamat","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chan, P.C., Liao, M.T., and Hsieh, P.S. (2019). The Dualistic Effect of COX-2-Mediated Signaling in Obesity and Insulin Resistance. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133115"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.cmet.2020.06.011","article-title":"The Gut Microbiota in Prediabetes and Diabetes: A Population-Based Cross-Sectional Study","volume":"32","author":"Wu","year":"2020","journal-title":"Cell Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1161\/CIRCRESAHA.120.316242","article-title":"Gut Microbiota and Cardiovascular Disease","volume":"127","author":"Witkowski","year":"2020","journal-title":"Circ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cell.2016.02.011","article-title":"Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk","volume":"165","author":"Zhu","year":"2016","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.cell.2020.02.016","article-title":"A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors","volume":"180","author":"Nemet","year":"2020","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/nm.4345","article-title":"Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug","volume":"23","author":"Wu","year":"2017","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1080\/14737159.2020.1711735","article-title":"Understanding the extent of the diagnostic potential of coagulation factors","volume":"20","author":"Favaloro","year":"2020","journal-title":"Expert Rev. Mol. Diagn"},{"key":"ref_34","first-page":"59","article-title":"Causality relationships between coagulation factors in type 2 diabetes mellitus: Path analysis approach","volume":"28","author":"Dayer","year":"2014","journal-title":"Med. J. Islam Repub. Iran"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1055\/s-0030-1265293","article-title":"Tissue factor and tissue factor pathway inhibitor as key regulators of global hemostasis: Measurement of their levels in coagulation assays","volume":"36","author":"Kasthuri","year":"2010","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s11892-007-0035-1","article-title":"Effects of hyperglycemia and hyperinsulinemia on the tissue factor pathway of blood coagulation","volume":"7","author":"Boden","year":"2007","journal-title":"Curr. Diab. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00011-017-1030-x","article-title":"Tissue factor levels in type 2 diabetes mellitus","volume":"66","author":"Soma","year":"2017","journal-title":"Inflamm. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00011-017-1121-8","article-title":"The interrelation of osteoarthritis and diabetes mellitus: Considering the potential role of interleukin-10 and in vitro models for further analysis","volume":"67","author":"Schwarz","year":"2018","journal-title":"Inflamm. Res."},{"key":"ref_39","first-page":"103","article-title":"Atherothrombosis: Role of tissue factor; link between diabetes, obesity and inflammation","volume":"45","author":"Meerarani","year":"2007","journal-title":"Indian J. Exp. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.cmet.2018.08.014","article-title":"The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality","volume":"28","author":"Chaudhuri","year":"2018","journal-title":"Cell Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1159\/000318775","article-title":"Tissue factor is induced by resistin in human coronary artery endothelial cells by the NF-kB-dependent pathway","volume":"48","author":"Calabro","year":"2011","journal-title":"J. Vasc. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1161\/ATVBAHA.115.306094","article-title":"Micro-RNA-126 Reduces the Blood Thrombogenicity in Diabetes Mellitus via Targeting of Tissue Factor","volume":"36","author":"Witkowski","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12933-018-0678-z","article-title":"MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes","volume":"17","author":"Witkowski","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12933-020-0993-z","article-title":"Vascular miR-181b controls tissue factor-dependent thrombogenicity and inflammation in type 2 diabetes","volume":"19","author":"Witkowski","year":"2020","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_45","first-page":"469","article-title":"Shortened Activated Partial Thromboplastin Time and Increased Superoxide Dismutase Levels Are Associated with Type 2 Diabetes Mellitus","volume":"48","author":"Fu","year":"2018","journal-title":"Ann. Clin. Lab. Sci"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"van der Toorn, F.A., de Mutsert, R., Lijfering, W.M., Rosendaal, F.R., and van Hylckama Vlieg, A. (2019). Glucose metabolism affects coagulation factors: The NEO study. J. Thromb. Haemost.","DOI":"10.1111\/jth.14573"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1160\/TH16-09-0716","article-title":"Obesity\/insulin resistance rather than liver fat increases coagulation factor activities and expression in humans","volume":"117","author":"Lallukka","year":"2017","journal-title":"Thromb. Haemost."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1160\/th14-05-0468","article-title":"The influence of type 2 diabetes on fibrin clot properties in patients with coronary artery disease","volume":"112","author":"Hvas","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.dsx.2019.01.049","article-title":"The importance of measurement of plasma fibrinogen level among patients with type- 2 diabetes mellitus","volume":"13","author":"Sultan","year":"2019","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/jjco\/hyd014","article-title":"Effect of IL-6 elevation in malignant pleural effusion on hyperfibrinogenemia in lung cancer patients","volume":"30","author":"Yamaguchi","year":"2000","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.thromres.2006.10.016","article-title":"Glycation of fibrinogen in uncontrolled diabetic patients and the effects of glycaemic control on fibrinogen glycation","volume":"120","author":"Pieters","year":"2007","journal-title":"Thromb. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.freeradbiomed.2016.04.023","article-title":"Post-translational oxidative modification of fibrinogen is associated with coagulopathy after traumatic injury","volume":"96","author":"White","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1177\/1076029618766254","article-title":"Thrombin Generation Assay Detects Moderate-Intensity Statin-Induced Reduction of Hypercoagulability in Diabetes","volume":"24","author":"Park","year":"2018","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e146","DOI":"10.1055\/s-0037-1608942","article-title":"Visceral Adiposity Is an Independent Determinant of Hypercoagulability as Measured by Thrombin Generation in Morbid Obesity","volume":"1","author":"Chitongo","year":"2017","journal-title":"TH Open"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Salvagno, G.L., Favaloro, E.J., Demonte, D., Gelati, M., Poli, G., Targher, G., and Lippi, G. (2019). Influence of hypertriglyceridemia, hyperbilirubinemia and hemolysis on thrombin generation in human plasma. Clin. Chem. Lab. Med.","DOI":"10.1515\/cclm-2019-0135"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12933-017-0515-9","article-title":"Hypofibrinolysis in diabetes: A therapeutic target for the reduction of cardiovascular risk","volume":"16","author":"Kearney","year":"2017","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.tmrv.2014.09.006","article-title":"The fibrinolytic system-more than fibrinolysis?","volume":"29","author":"Draxler","year":"2015","journal-title":"Transfus. Med. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1182\/blood-2013-04-494641","article-title":"Diabetes is associated with posttranslational modifications in plasminogen resulting in reduced plasmin generation and enzyme-specific activity","volume":"122","author":"Ajjan","year":"2013","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Canecki-Varzic, S., Prpic-Krizevac, I., and Bilic-Curcic, I. (2016). Plasminogen activator inhibitor-1 concentrations and bone mineral density in postmenopausal women with type 2 diabetes mellitus. BMC Endocr. Disord., 16.","DOI":"10.1186\/s12902-016-0094-x"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12933-019-0850-0","article-title":"Predictors of neutrophil extracellular traps markers in type 2 diabetes mellitus: Associations with a prothrombotic state and hypofibrinolysis","volume":"18","author":"Bryk","year":"2019","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1097\/NHH.0000000000000584","article-title":"Hypoglycemia in Diabetes Mellitus","volume":"35","author":"Freeland","year":"2017","journal-title":"Home Healthc. Now"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/s13139-018-00568-5","article-title":"Tracer Accumulation in Relation to Venous Thrombus on (18)F-DOPA PET\/CT in a Case of Persistent Hyperinsulinemic Hypoglycemia of Infancy","volume":"53","author":"Arora","year":"2019","journal-title":"Nucl. Med. Mol. Imaging"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1080\/14779072.2016.1215916","article-title":"Hypoglycaemia, thrombosis and vascular events in diabetes","volume":"14","author":"King","year":"2016","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12959-019-0206-8","article-title":"Effects of glycemic control and hypoglycemia on Thrombus formation assessed using automated microchip flow chamber system: An exploratory observational study","volume":"17","author":"Yamamoto","year":"2019","journal-title":"Thromb. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/j.metabol.2016.09.001","article-title":"Effects of equivalent sympathetic activation during hypoglycemia on endothelial function and pro-atherothrombotic balance in healthy individuals and obese standard treated type 2 diabetes","volume":"65","author":"Joy","year":"2016","journal-title":"Metabolism"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.2337\/dc18-0050","article-title":"Prolonged Prothrombotic Effects of Antecedent Hypoglycemia in Individuals with Type 2 Diabetes","volume":"41","author":"Chow","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1185\/03007995.2016.1168291","article-title":"Prevalence and co-prevalence of comorbidities among patients with type 2 diabetes mellitus","volume":"32","author":"Iglay","year":"2016","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1111\/joim.12299","article-title":"Obesity as a causal risk factor for deep venous thrombosis: A Mendelian randomization study","volume":"277","author":"Klovaite","year":"2015","journal-title":"J. Intern. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1111\/j.1538-7836.2012.04828.x","article-title":"The relationship between body mass index, activated protein C resistance and risk of venous thrombosis","volume":"10","author":"Christiansen","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/oby.2003.131","article-title":"Weight loss reduces tissue factor in morbidly obese patients","volume":"11","author":"Kopp","year":"2003","journal-title":"Obes. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10557-012-6398-9","article-title":"Beyond hyperglycemia in diabetes: Role of statin treatment on thrombogenesis triggered by inflammation: Editorial to: \u201cImpact of statins on the coagulation status of type 2 diabetes patients evaluated by a novel thrombin-generations assay\u201d by Ferroni, P","volume":"26","author":"Perego","year":"2012","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3343\/alm.2015.35.1.15","article-title":"Influence of blood lipids on global coagulation test results","volume":"35","author":"Kim","year":"2015","journal-title":"Ann. Lab. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S1734-1140(10)70372-8","article-title":"Hemostatic effects of fenofibrate in patients with mixed dyslipidemia and impaired fasting glucose","volume":"62","author":"Krysiak","year":"2010","journal-title":"Pharmacol. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ijcard.2018.05.098","article-title":"LDL extracellular vesicle coagulation protein levels change after initiation of statin therapy. Findings from the METEOR trial","volume":"271","author":"Zhang","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.jhep.2019.06.021","article-title":"The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis","volume":"71","author":"Younossi","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1111\/j.1478-3231.2010.02375.x","article-title":"Increased coagulation factor VIII, IX, XI and XII activities in non-alcoholic fatty liver disease","volume":"31","author":"Kotronen","year":"2011","journal-title":"Liver Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/hep.26510","article-title":"Prothrombotic factors in histologically proven nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","volume":"59","author":"Verrijken","year":"2014","journal-title":"Hepatology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1056\/NEJMoa1409312","article-title":"Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents","volume":"371","author":"Mauri","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"ASCEND Study Collaborative Group, Bowman, L., Mafham, M., Wallendszus, K., Stevens, W., Buck, G., Barton, J., Murphy, K., Aung, T., and Haynes, R. (2018). Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N. Engl. J. Med., 379, 1529\u20131539.","DOI":"10.1056\/NEJMoa1804988"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1177\/1479164110383723","article-title":"Coagulation and fibrinolysis in diabetes","volume":"7","author":"Alzahrani","year":"2010","journal-title":"Diab. Vasc. Dis. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"103631","DOI":"10.1016\/j.jprot.2019.103631","article-title":"Plasma metabonomics and proteomics studies on the anti-thrombosis mechanism of aspirin eugenol ester in rat tail thrombosis model","volume":"215","author":"Ma","year":"2020","journal-title":"J. Proteom."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"S103","DOI":"10.2337\/dc19-S010","article-title":"10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2019","volume":"42","year":"2019","journal-title":"Diabetes Care"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/S0140-6736(09)60503-1","article-title":"Aspirin in the primary and secondary prevention of vascular disease: Collaborative meta-analysis of individual participant data from randomised trials","volume":"373","author":"Baigent","year":"2009","journal-title":"Lancet"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1161\/CIRCULATIONAHA.120.045465","article-title":"Antithrombotic therapy for atherosclerotic cardiovascular disease risk mitigation in patients with coronary artery disease and diabetes mellitus","volume":"142","author":"Capodanno","year":"2020","journal-title":"Circulation"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1160\/TH11-12-0876","article-title":"The extent of P2Y12 inhibition by clopidogrel in diabetes mellitus patients with acute coronary syndrome is not related to glycaemic control: Roles of white blood cell count and body weight","volume":"108","author":"Morel","year":"2012","journal-title":"Thromb. Haemost."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ahj.2009.11.014","article-title":"Triple antiplatelet therapy reduces ischemic events after drug-eluting stent implantation: Drug-Eluting stenting followed by Cilostazol treatment REduces Adverse Serious cardiac Events (DECREASE registry)","volume":"159","author":"Lee","year":"2010","journal-title":"Am. Heart J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1016\/j.ehj.2004.08.008","article-title":"Picotamide versus aspirin in diabetic patients with peripheral arterial disease: Has David defeated Goliath?","volume":"25","author":"Gresele","year":"2004","journal-title":"Eur. Heart J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.jvs.2007.10.009","article-title":"Long-term safety of cilostazol in patients with peripheral artery disease: The CASTLE study (Cilostazol: A Study in Long-term Effects)","volume":"47","author":"Hiatt","year":"2008","journal-title":"J. Vasc. Surg."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1182\/blood-2017-09-804666","article-title":"Warfarin alters vitamin K metabolism: A surprising mechanism of VKORC1 uncoupling necessitates an additional reductase","volume":"131","author":"Rishavy","year":"2018","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.amjcard.2019.10.033","article-title":"Safety and Efficacy of Direct Oral Anticoagulants Versus Warfarin in Patients with Chronic Kidney Disease and Atrial Fibrillation","volume":"125","author":"Makani","year":"2020","journal-title":"Am. J. Cardiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.ahj.2015.07.006","article-title":"Efficacy and safety of rivaroxaban in patients with diabetes and nonvalvular atrial fibrillation: The Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF Trial)","volume":"170","author":"Bansilal","year":"2015","journal-title":"Am. Heart J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1111\/dom.13787","article-title":"Effectiveness and safety of rivaroxaban and warfarin for prevention of major adverse cardiovascular or limb events in patients with non-valvular atrial fibrillation and type 2 diabetes","volume":"21","author":"Baker","year":"2019","journal-title":"Diabetes Obes. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"130","DOI":"10.21037\/cdt-20-859","article-title":"A narrative review of low-dose rivaroxaban in patients with atherothrombotic cardiovascular disease: Vascular protection beyond anticoagulation","volume":"11","author":"Rocha","year":"2021","journal-title":"Cardiovasc. Diagn. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1016\/j.jacc.2014.02.549","article-title":"Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes","volume":"63","author":"Hylek","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ijcard.2015.05.141","article-title":"Comparison of dabigatran versus warfarin in diabetic patients with atrial fibrillation: Results from the RE-LY trial","volume":"196","author":"Brambatti","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6573","DOI":"10.1038\/s41598-019-43083-z","article-title":"Sulfenamide and Sulfonamide Derivatives of Metformin\u2014A New Option to Improve Endothelial Function and Plasma Haemostasis","volume":"9","author":"Huttunen","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Witkowski, M., Friebel, J., Tabaraie, T., Grabitz, S., Dorner, A., Taghipour, L., Jakobs, K., Stratmann, B., Tschoepe, D., and Landmesser, U. (2020). Metformin Is Associated with Reduced Tissue Factor Procoagulant Activity in Patients with Poorly Controlled Diabetes. Cardiovasc. Drugs Ther.","DOI":"10.1007\/s10557-020-07040-7"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.atherosclerosis.2007.07.020","article-title":"Rosiglitazone produces a greater reduction in circulating platelet activity compared with gliclazide in patients with type 2 diabetes mellitus\u2014An effect probably mediated by direct platelet PPARgamma activation","volume":"197","author":"Khanolkar","year":"2008","journal-title":"Atherosclerosis"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.2337\/dc13-2471","article-title":"Lifestyle and metformin interventions have a durable effect to lower CRP and tPA levels in the diabetes prevention program except in those who develop diabetes","volume":"37","author":"Goldberg","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Verdoia, M., Pergolini, P., Rolla, R., Ceccon, C., Caputo, M., Aimaretti, G., Suryapranata, H., and De Luca, G. (2018). Use of Metformin and Platelet Reactivity in Diabetic Patients Treated with Dual Antiplatelet Therapy. Exp. Clin. Endocrinol. Diabetes.","DOI":"10.1055\/a-0787-1382"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11010-012-1551-0","article-title":"Proteomic analysis of rosiglitazone and guggulsterone treated 3T3-L1 preadipocytes","volume":"376","author":"Pal","year":"2013","journal-title":"Mol. Cell Biochem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e100","DOI":"10.1016\/j.thromres.2011.07.007","article-title":"Anticoagulant effects of an antidiabetic drug on monocytes in vitro","volume":"128","author":"Henriksson","year":"2011","journal-title":"Thromb. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.2337\/diabetes.52.7.1851","article-title":"Insulin acutely increases fibrinogen production in individuals with type 2 diabetes but not in individuals without diabetes","volume":"52","author":"Barazzoni","year":"2003","journal-title":"Diabetes"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1603827","article-title":"Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1160\/TH16-07-0586","article-title":"Glucagon-like peptide 1-related peptides increase nitric oxide effects to reduce platelet activation","volume":"117","author":"Barale","year":"2017","journal-title":"Thromb. Haemost."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Simeone, P., Liani, R., Tripaldi, R., Di Castelnuovo, A., Guagnano, M.T., Tartaro, A., Bonadonna, R.C., Federico, V., Cipollone, F., and Consoli, A. (2018). Thromboxane-Dependent Platelet Activation in Obese Subjects with Prediabetes or Early Type 2 Diabetes: Effects of Liraglutide- or Lifestyle Changes-Induced Weight Loss. Nutrients, 10.","DOI":"10.3390\/nu10121872"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1056\/NEJMoa2022190","article-title":"Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure","volume":"383","author":"Packer","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e159","DOI":"10.2337\/dc19-1177","article-title":"Effect of Empagliflozin on Endothelial Function in Patients with Type 2 Diabetes and Cardiovascular Disease: Results from the Multicenter, Randomized, Placebo-Controlled, Double-Blind EMBLEM Trial","volume":"42","author":"Tanaka","year":"2019","journal-title":"Diabetes Care"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"865","DOI":"10.33594\/000000178","article-title":"Empagliflozin and Dapagliflozin Reduce ROS Generation and Restore NO Bioavailability in Tumor Necrosis Factor alpha-Stimulated Human Coronary Arterial Endothelial Cells","volume":"53","author":"Uthman","year":"2019","journal-title":"Cell Physiol. Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"107703","DOI":"10.1016\/j.jdiacomp.2020.107703","article-title":"Empagliflozin decreases the plasma concentration of plasminogen activator inhibitor-1 (PAI-1) in patients with type 2 diabetes: Association with improvement of fibrinolysis","volume":"34","author":"Sakurai","year":"2020","journal-title":"J. Diabetes Complicat."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1016\/S0140-6736(16)00271-3","article-title":"Management of obesity","volume":"387","author":"Bray","year":"2016","journal-title":"Lancet"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.soard.2018.03.022","article-title":"Effects of gastric bypass followed by a randomized study of physical training on markers of coagulation activation, fibrin clot properties, and fibrinolysis","volume":"14","author":"Stolberg","year":"2018","journal-title":"Surg. Obes. Relat. Dis."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"7140754","DOI":"10.1155\/2018\/7140754","article-title":"Effects of 6 Months of Active Commuting and Leisure-Time Exercise on Fibrin Turnover in Sedentary Individuals with Overweight and Obesity: A Randomised Controlled Trial","volume":"2018","author":"Gram","year":"2018","journal-title":"J. Obes."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.clnu.2016.08.026","article-title":"Effects of exchanging carbohydrate or monounsaturated fat with saturated fat on inflammatory and thrombogenic responses in subjects with abdominal obesity: A randomized controlled trial","volume":"36","author":"Teng","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Horber, S., Lehmann, R., Fritsche, L., Machann, J., Birkenfeld, A.L., Haring, H.U., Stefan, N., Heni, M., Fritsche, A., and Peter, A. (2021). Lifestyle intervention improves prothrombotic coagulation profile in individuals at high-risk for type 2 diabetes. J. Clin. Endocrinol. Metab.","DOI":"10.1210\/clinem\/dgab124"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s11239-017-1541-x","article-title":"Effects of statin therapy on platelet reactivity after percutaneous coronary revascularization in patients with acute coronary syndrome","volume":"44","author":"Toso","year":"2017","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"235","DOI":"10.20452\/pamw.140","article-title":"Antiplatelet effects of micronized fenofibrate in subjects with dyslipidemia","volume":"117","author":"Undas","year":"2007","journal-title":"Pol. Arch. Med. Wewn"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1160\/TH10-12-0810","article-title":"Atorvastatin reduces thrombin generation and expression of tissue factor, P-selectin and GPIIIa on platelet-derived microparticles in patients with peripheral arterial occlusive disease","volume":"106","author":"Mobarrez","year":"2011","journal-title":"Thromb. Haemost."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1055\/s-0038-1676863","article-title":"PCSK9 in Haemostasis and Thrombosis: Possible Pleiotropic Effects of PCSK9 Inhibitors in Cardiovascular Prevention","volume":"119","author":"Paciullo","year":"2019","journal-title":"Thromb. Haemost."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/11\/2419\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:08:51Z","timestamp":1760162931000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/11\/2419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,29]]},"references-count":119,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["jcm10112419"],"URL":"https:\/\/doi.org\/10.3390\/jcm10112419","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,29]]}}}