{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:05:34Z","timestamp":1791993934783,"version":"4.4.0"},"reference-count":193,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health\u2014Ricerca Corrente to IRCCS MultiMedica","award":["SG-2021-12372752"],"award-info":[{"award-number":["SG-2021-12372752"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Low-grade inflammation (LGI) represents a key driver of type 2 diabetes (T2D) and its associated cardiovascular diseases (CVDs). Indeed, inflammatory markers such as hs-CRP and IL-6 predict the development of T2D and its complications, suggesting that LGI already increases before T2D diagnosis and remains elevated even after treatment. Overnutrition, unhealthy diets, physical inactivity, obesity, and aging are all recognized triggers of LGI, promoting insulin resistance and sustaining the pathogenesis of T2D. Once developed, and even before frank appearance, people with T2D undergo a pathological metabolic remodeling, with an alteration of multiple CVD risk factors, i.e., glycemia, lipids, blood pressure, and renal function. In turn, such variables foster a range of inflammatory pathways and mechanisms, e.g., immune cell stimulation, the accrual of senescent cells, long-lasting epigenetic changes, and trained immunity, which are held to chronically fuel LGI at the systemic and tissue levels. Targeting of CVD risk factors partially ameliorates LGI. However, some long-lasting inflammatory pathways are unaffected by common therapies, and LGI burden is still increased in many T2D patients, a phenomenon possibly underlying the residual inflammatory risk (i.e., having hs-CRP &gt; 2 mg\/dL despite optimal LDL cholesterol control). On the other hand, selected disease-modifying drugs, e.g., GLP-1RA, seem to also act on the pathogenesis of T2D, curbing the inflammatory trajectory of the disease and possibly preventing it if introduced early. In addition, selected trials demonstrated the potential of canonical anti-inflammatory therapies in reducing the rate of CVDs in patients with this condition or at high risk for it, many of whom had T2D. Since colchicine, an inhibitor of immune cell activation, is now approved for the prevention of CVDs, it might be worth exploring a possible therapeutic paradigm to identify subjects with T2D and an increased LGI burden to treat them with this drug. Upcoming studies will reveal whether disease-modifying drugs reverse early T2D by suppressing sources of LGI and whether colchicine has a broad benefit in people with this condition.<\/jats:p>","DOI":"10.3390\/cells13191662","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T12:01:54Z","timestamp":1728388914000},"page":"1662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Inflammatory Trajectory of Type 2 Diabetes: Novel Opportunities for Early and Late Treatment"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1187-5296","authenticated-orcid":false,"given":"Valeria","family":"Pellegrini","sequence":"first","affiliation":[{"name":"IRCCS MultiMedica, Via Fantoli 16\/15, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2224-4615","authenticated-orcid":false,"given":"Rosalba","family":"La Grotta","sequence":"additional","affiliation":[{"name":"IRCCS MultiMedica, Via Fantoli 16\/15, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Carreras","sequence":"additional","affiliation":[{"name":"IRCCS MultiMedica, Via Fantoli 16\/15, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8477-8519","authenticated-orcid":false,"given":"Angelica","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Cardiac Rehabilitation Unit of Bari Institute, Istituti Clinici Scientifici Maugeri IRCCS, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9947-6778","authenticated-orcid":false,"given":"Jacopo","family":"Sabbatinelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences (DISCLIMO), Universit\u00e0 Politecnica delle Marche, 60127 Ancona, Italy"},{"name":"Clinic of Laboratory and Precision Medicine, IRCCS INRCA, 60127 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9606-1144","authenticated-orcid":false,"given":"Fabiola","family":"Olivieri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences (DISCLIMO), Universit\u00e0 Politecnica delle Marche, 60127 Ancona, Italy"},{"name":"Advanced Technology Center for Aging Research, IRCCS INRCA, 60127 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8431-8160","authenticated-orcid":false,"given":"Cesare Celeste","family":"Berra","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, IRCCS Multimedica, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ceriello","sequence":"additional","affiliation":[{"name":"IRCCS MultiMedica, Via Fantoli 16\/15, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2959-2658","authenticated-orcid":false,"given":"Francesco","family":"Prattichizzo","sequence":"additional","affiliation":[{"name":"IRCCS MultiMedica, Via Fantoli 16\/15, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.15420\/ecr.2018.33.1","article-title":"The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives","volume":"14","author":"Tsalamandris","year":"2019","journal-title":"Eur. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nature21363","article-title":"Inflammation, metaflammation and immunometabolic disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S244","DOI":"10.2337\/dcS15-3015","article-title":"Anti-inflammatory Agents in the Treatment of Diabetes and Its Vascular Complications","volume":"39","author":"Pollack","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1056\/NEJMoa1912388","article-title":"Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction","volume":"381","author":"Tardif","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jacc.2012.10.027","article-title":"Low-dose colchicine for secondary prevention of cardiovascular disease","volume":"61","author":"Nidorf","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1056\/NEJMoa2021372","article-title":"Colchicine in Patients with Chronic Coronary Disease","volume":"383","author":"Nidorf","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_8","first-page":"543","article-title":"Low-grade systemic inflammation and the development of metabolic diseases: From the molecular evidence to the clinical practice","volume":"83","author":"Escobedo","year":"2015","journal-title":"Cir. Cir."},{"key":"ref_9","first-page":"e30225","article-title":"Role of High-Sensitivity C-reactive Protein (Hs-CRP) in Non-communicable Diseases: A Review","volume":"14","author":"Banait","year":"2022","journal-title":"Cureus"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1126\/science.7678183","article-title":"Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance","volume":"259","author":"Hotamisligil","year":"1993","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0047-6374(03)00027-7","article-title":"Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes","volume":"124","author":"Pedersen","year":"2003","journal-title":"Mech. Ageing Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"166","DOI":"10.2337\/dc12-0702","article-title":"Inflammatory markers and risk of type 2 diabetes: A systematic review and meta-analysis","volume":"36","author":"Wang","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.1093\/eurheartj\/ehaa160","article-title":"Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: Secondary analyses from the Cardiovascular Inflammation Reduction Trial","volume":"41","author":"Ridker","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1001\/jama.286.3.327","article-title":"C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus","volume":"286","author":"Pradhan","year":"2001","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.2337\/diabetes.51.5.1596","article-title":"West of Scotland Coronary Prevention Study. C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study","volume":"51","author":"Freeman","year":"2002","journal-title":"Diabetes"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.2337\/diabetes.52.7.1799","article-title":"Atherosclerosis Risk in Communities Study. Low-grade systemic inflammation and the development of type 2 diabetes: The atherosclerosis risk in communities study","volume":"52","author":"Duncan","year":"2003","journal-title":"Diabetes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.2337\/diacare.22.12.1971","article-title":"Body mass index, diabetes, and C-reactive protein among, U.S. adults","volume":"22","author":"Ford","year":"1999","journal-title":"Diabetes Care"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.2337\/diacare.28.10.2497","article-title":"Elevated C-reactive protein is a predictor of the development of diabetes in a general Japanese population: The Hisayama Study","volume":"28","author":"Doi","year":"2005","journal-title":"Diabetes Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1161\/CIRCULATIONAHA.114.009990","article-title":"Chronic inflammatory disorders and risk of type 2 diabetes mellitus, coronary heart disease, and stroke: A population-based cohort study","volume":"130","author":"Dregan","year":"2014","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cmet.2021.12.012","article-title":"Why does obesity cause diabetes?","volume":"34","author":"Klein","year":"2022","journal-title":"Cell Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1172\/JCI45887","article-title":"Adipose tissue remodeling and obesity","volume":"121","author":"Sun","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1210\/jc.2006-1055","article-title":"Relationship between adipocyte size and adipokine expression and secretion","volume":"92","author":"Skurk","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5063","DOI":"10.1172\/JCI137556","article-title":"Hypoxia-inducible factors and diabetes","volume":"130","author":"Gunton","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e20191593","DOI":"10.1084\/jem.20191593","article-title":"The pleiotropic roles of leptin in metabolism, immunity, and cancer","volume":"218","author":"Prattichizzo","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/j.immuni.2021.04.014","article-title":"Signals of pseudo-starvation unveil the amino acid transporter SLC7A11 as key determinant in the control of Treg cell proliferative potential","volume":"54","author":"Procaccini","year":"2021","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/CIRCRESAHA.120.314458","article-title":"Adiponectin, Leptin and Cardiovascular Disorders","volume":"128","author":"Zhao","year":"2021","journal-title":"Circ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4049","DOI":"10.3390\/ijerph110404049","article-title":"Relationship between obesity, adipocytokines and inflammatory markers in type 2 diabetes: Relevance for cardiovascular risk prevention","volume":"11","author":"Rajkovic","year":"2014","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e2167","DOI":"10.1038\/cddis.2016.54","article-title":"Local proliferation initiates macrophage accumulation in adipose tissue during obesity","volume":"7","author":"Zheng","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1194\/jlr.M800019-JLR200","article-title":"Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice","volume":"49","author":"Murano","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zatterale, F., Longo, M., Naderi, J., Raciti, G.A., Desiderio, A., Miele, C., and Beguinot, F. (2020). Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.01607"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1146\/annurev-nutr-071811-150623","article-title":"Mechanisms of inflammatory responses in obese adipose tissue","volume":"32","author":"Sun","year":"2012","journal-title":"Annu. Rev. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ca\u00ebr, C., Rouault, C., Le Roy, T., Poitou, C., Aron-Wisnewsky, J., Torcivia, A., Bichet, J.C., Cl\u00e9ment, K., Guerre-Millo, M., and Andr\u00e9, S. (2017). Immune cell-derived cytokines contribute to obesity-related inflammation, fibrogenesis and metabolic deregulation in human adipose tissue. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-02660-w"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1615\/CritRevEukaryotGeneExpr.2017019712","article-title":"Role of Interleukin-6 in Development of Insulin Resistance and Type 2 Diabetes Mellitus","volume":"27","author":"Rehman","year":"2017","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_34","first-page":"e14607","article-title":"Mechanisms of muscle insulin resistance and the cross-talk with liver and adipose tissue","volume":"8","author":"Nayak","year":"2020","journal-title":"Physiol. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tabula Muris Consortium (2020). A single-cell transcriptomic atlas characterizes ageing tissues in the mouse. Nature, 583, 590\u2013595.","DOI":"10.1038\/s41586-020-2496-1"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","article-title":"Cellular Senescence: Defining a Path Forward","volume":"179","author":"Gorgoulis","year":"2019","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/s41366-021-00757-x","article-title":"Cellular senescence and its role in white adipose tissue","volume":"45","author":"Smith","year":"2021","journal-title":"Int. J. Obes."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1002\/oby.23202","article-title":"Senescent cells in human adipose tissue: A cross-sectional study","volume":"29","author":"Lytle","year":"2021","journal-title":"Obesity"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E6301","DOI":"10.1073\/pnas.1515386112","article-title":"JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age","volume":"112","author":"Xu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1007\/s11357-022-00536-0","article-title":"Senescent macrophages in the human adipose tissue as a source of inflammaging","volume":"44","author":"Matacchione","year":"2022","journal-title":"Geroscience"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.2337\/db10-0398","article-title":"Adipose tissue endothelial cells from obese human subjects: Differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence","volume":"59","author":"Villaret","year":"2010","journal-title":"Diabetes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e12950","DOI":"10.1111\/acel.12950","article-title":"Targeting senescent cells alleviates obesity-induced metabolic dysfunction","volume":"18","author":"Palmer","year":"2019","journal-title":"Aging Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.cmet.2021.12.008","article-title":"Targeting p21 for diabetes: Another choice of senotherapy","volume":"34","author":"Kondoh","year":"2022","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.arr.2017.10.003","article-title":"Inflammageing and metaflammation: The yin and yang of type 2 diabetes","volume":"41","author":"Prattichizzo","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging. An evolutionary perspective on immunosenescence","volume":"908","author":"Franceschi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: A new immune-metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1007\/BF00400649","article-title":"The role of interleukin-1 in the pathogenesis of IDDM","volume":"39","year":"1996","journal-title":"Diabetologia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1056\/NEJMoa065213","article-title":"Interleukin-1-receptor antagonist in type 2 diabetes mellitus","volume":"356","author":"Larsen","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.diabet.2020.01.002","article-title":"Reduction in HbA1c with SGLT2 inhibitors vs. DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c: A systematic review of randomized controlled trials","volume":"46","author":"Scheen","year":"2020","journal-title":"Diabetes Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.2337\/diacare.21.12.2050","article-title":"Efficacy and safety of acarbose in metformin-treated patients with type 2 diabetes","volume":"21","author":"Rosenstock","year":"1998","journal-title":"Diabetes Care"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1016\/j.jacc.2018.03.002","article-title":"Anti-Inflammatory Therapy with Canakinumab for the Prevention and Management of Diabetes","volume":"71","author":"Everett","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1517\/13543784.2015.974804","article-title":"Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease","volume":"24","author":"Esser","year":"2015","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7326\/0003-4819-159-1-201307020-00003","article-title":"Targeting Inflammation Using Salsalate in Type 2 Diabetes Study Team. Salicylate (salsalate) in patients with type 2 diabetes: A randomized trial","volume":"159","author":"Goldfine","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"346","DOI":"10.7326\/0003-4819-152-6-201003160-00004","article-title":"TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes) Study Team. The effects of salsalate on glycemic control in patients with type 2 diabetes: A randomized trial","volume":"152","author":"Goldfine","year":"2010","journal-title":"Ann. Intern. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00592-011-0329-2","article-title":"Salsalate improves glycemic control in patients with newly diagnosed type 2 diabetes","volume":"50","author":"Faghihimani","year":"2013","journal-title":"Acta Diabetol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mohammadnia, N., Los, J., Opstal, T.S.J., Fiolet, A.T.L., Eikelboom, J.W., Mosterd, A., Nidorf, S.M., Budgeon, C.A., Tijssen, J.G.P., and Thompson, P.L. (2023). Colchicine and diabetes in patients with chronic coronary artery disease: Insights from the LoDoCo2 randomized controlled trial. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1244529"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.ejim.2010.09.010","article-title":"Colchicine in clinical medicine. A guide for internists","volume":"21","author":"Cocco","year":"2010","journal-title":"Eur. J. Intern. Med."},{"key":"ref_58","unstructured":"American Diabetes Association Professional Practice Committee (2024). Summary of Revisions: Standards of Care in Diabetes\u20142024. Diabetes Care, 47, S5\u2013S10."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s00125-017-4467-0","article-title":"HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes","volume":"61","author":"Slieker","year":"2018","journal-title":"Diabetologia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.2337\/db20-0568","article-title":"A High Glycemic Burden Relates to Functional and Metabolic Alterations of Human Monocytes in Patients with Type 1 Diabetes","volume":"69","author":"Thiem","year":"2020","journal-title":"Diabetes"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00018-023-05010-4","article-title":"Increasing HbA1c is associated with reduced CD8+ T cell functionality in response to influenza virus in a TCR-dependent manner in individuals with diabetes mellitus","volume":"81","author":"Hulme","year":"2024","journal-title":"Cell Mol. Life Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1038\/s41467-022-30068-2","article-title":"Glycaemic control is associated with SARS-CoV-2 breakthrough infections in vaccinated patients with type 2 diabetes","volume":"13","author":"Marfella","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"62","DOI":"10.4068\/cmj.2021.57.1.62","article-title":"Relationship between hs-CRP and HbA1c in Diabetes Mellitus Patients: 2015\u20132017 Korean National Health and Nutrition Examination Survey","volume":"57","author":"Seo","year":"2021","journal-title":"Chonnam. Med. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5585938","DOI":"10.1155\/2021\/5585938","article-title":"The Association of Hemoglobin A1c and Fasting Glucose Levels with hs-CRP in Adults Not Diagnosed with Diabetes from the KNHANES, 2017","volume":"2021","author":"Seo","year":"2021","journal-title":"J. Diabetes Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3555","DOI":"10.2147\/DMSO.S323009","article-title":"Plasma Nesfatin-1: Potential Predictor and Diagnostic Biomarker for Cognitive Dysfunction in T2DM Patient","volume":"14","author":"Xu","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"175","DOI":"10.24293\/ijcpml.v29i2.1972","article-title":"IL-6 Levels Analysis Controlled in Type 2 Diabetes Mellitus Patients and Uncontrolled","volume":"29","author":"Todingan","year":"2023","journal-title":"Indones. J. Clin. Pathol. Med. Lab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12950-016-0142-3","article-title":"Effects of metformin on blood and urine pro-inflammatory mediators in patients with type 2 diabetes","volume":"13","author":"Chen","year":"2016","journal-title":"J. Inflamm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.2147\/DDDT.S208327","article-title":"Effects of acarbose and metformin on the inflammatory state in newly diagnosed type 2 diabetes patients: A one-year randomized clinical study","volume":"13","author":"Mo","year":"2019","journal-title":"Drug Des. Devel Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jacc.2006.08.054","article-title":"Anti-inflammatory effects of pioglitazone and\/or simvastatin in high cardiovascular risk patients with elevated high sensitivity C-reactive protein: The PIOSTAT Study","volume":"49","author":"Hanefeld","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1161\/CIRCRESAHA.116.308445","article-title":"Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status","volume":"119","author":"Cameron","year":"2016","journal-title":"Circ. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"a025932","DOI":"10.1101\/cshperspect.a025932","article-title":"Metformin: A Hopeful Promise in Aging Research","volume":"6","author":"Novelle","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1016\/j.jacc.2005.03.041","article-title":"Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: Results from the pioneer study","volume":"45","author":"Marx","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_73","first-page":"27","article-title":"Hypoglycemic agents and potential anti-inflammatory activity","volume":"9","author":"Kothari","year":"2016","journal-title":"J. Inflamm. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/ni.3659","article-title":"Postprandial macrophage-derived IL-1\u03b2 stimulates insulin, and both synergistically promote glucose disposal and inflammation","volume":"18","author":"Dror","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mce.2008.09.030","article-title":"Insulin exhibits short-term anti-inflammatory but long-term proinflammatory effects in vitro","volume":"298","author":"Iwasaki","year":"2009","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_76","unstructured":"(2024, August 01). Available online: https:\/\/www.siditalia.it\/pdf\/LG_379_diabete_ed2022_feb2023.pdf."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Jukema, R.A., Ahmed, T.A.N., and Tardif, J.C. (2019). Does low-density lipoprotein cholesterol induce inflammation? If so, does it matter? Current insights and future perspectives for novel therapies. BMC Med., 17.","DOI":"10.1186\/s12916-019-1433-3"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1161\/01.ATV.0000021150.63480.CD","article-title":"Circulating oxidized LDL is associated with subclinical atherosclerosis development and inflammatory cytokines (AIR Study)","volume":"22","author":"Hulthe","year":"2002","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1056\/NEJMoa042378","article-title":"Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators. C-reactive protein levels and outcomes after statin therapy","volume":"352","author":"Ridker","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jare.2023.05.003","article-title":"J-shaped association between LDL cholesterol and cardiovascular events: A longitudinal primary prevention cohort of over 2.4 million people nationwide","volume":"58","author":"Park","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1056\/NEJMoa021993","article-title":"Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events","volume":"347","author":"Ridker","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1161\/CIRCRESAHA.121.319077","article-title":"Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease","volume":"128","author":"Ridker","year":"2021","journal-title":"Circ. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1016\/j.amjcard.2007.01.062","article-title":"Comparison of effects of ezetimibe\/simvastatin versus simvastatin versus atorvastatin in reducing C-reactive protein and low-density lipoprotein cholesterol levels","volume":"99","author":"Pearson","year":"2007","journal-title":"Am. J. Cardiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/cvr\/cvae034","article-title":"META-LIPID Group. Effect of lipid-lowering therapies on C-reactive protein levels: A comprehensive meta-analysis of randomized controlled trials","volume":"120","author":"Xie","year":"2024","journal-title":"Cardiovasc. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"154752","DOI":"10.1016\/j.cyto.2019.154752","article-title":"Statins influence biomarkers of low grade inflammation in apparently healthy people or patients with chronic diseases: A systematic review and meta-analysis of randomized clinical trials","volume":"123","author":"Milajerdi","year":"2019","journal-title":"Cytokine"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"117180","DOI":"10.1016\/j.atherosclerosis.2023.06.971","article-title":"Evidence of an anti-inflammatory effect of PCSK9 inhibitors within the human atherosclerotic plaque","volume":"378","author":"Marfella","year":"2023","journal-title":"Atherosclerosis"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"531","DOI":"10.7150\/thno.80289","article-title":"SIRT3 mediates the effects of PCSK9 inhibitors on inflammation, autophagy, and oxidative stress in endothelial cells","volume":"13","author":"Prattichizzo","year":"2023","journal-title":"Theranostics"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1161\/01.ATV.0000029781.31325.66","article-title":"Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women","volume":"22","author":"Bermudez","year":"2002","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1161\/01.CIR.0000136581.59584.0E","article-title":"C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study","volume":"110","author":"Rutter","year":"2004","journal-title":"Circulation"},{"key":"ref_90","first-page":"975","article-title":"Reduction of C-reactive protein and the use of anti-hypertensives","volume":"3","author":"Savoia","year":"2007","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1136\/heart.87.3.252","article-title":"Impact of angiotensin converting enzyme inhibition on post-coronary artery bypass interleukin 6 release","volume":"87","author":"Brull","year":"2002","journal-title":"Heart"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1161\/01.HYP.0000226046.58883.32","article-title":"Val-MARC Investigators. Valsartan, blood pressure reduction, and C-reactive protein: Primary report of the Val-MARC trial","volume":"48","author":"Ridker","year":"2006","journal-title":"Hypertension"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/sj.jhh.1002101","article-title":"Angiotensin II and inflammation: The effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade","volume":"21","author":"Dandona","year":"2007","journal-title":"J. Hum. Hypertens."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.amjhyper.2006.08.006","article-title":"Antihypertensive medications and C-reactive protein in the multi-ethnic study of atherosclerosis","volume":"20","author":"Palmas","year":"2007","journal-title":"Am. J. Hypertens."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.2337\/dc12-1711","article-title":"Changes in A1C levels are significantly associated with changes in levels of the cardiovascular risk biomarker hs-CRP: Results from the SteP study","volume":"36","author":"Schnell","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cmet.2016.05.011","article-title":"Metformin as a Tool to Target Aging","volume":"23","author":"Barzilai","year":"2016","journal-title":"Cell Metab."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1056\/NEJM199704033361401","article-title":"Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men","volume":"336","author":"Ridker","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1056\/NEJM199704033361409","article-title":"Inflammation, atherosclerosis, and ischemic events\u2014Exploring the hidden side of the moon","volume":"336","author":"Maseri","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1001\/jama.2016.16951","article-title":"Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial","volume":"316","author":"Nicholls","year":"2016","journal-title":"JAMA"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Mach, F., Visseren, F.L.J., Cater, N.B., Salhi, N., Soronen, J., Ray, K.K., Delgado, V., Jukema, J.W., Laufs, U., and Zamorano, J.-L. (2024). Addressing residual risk beyond statin therapy: New targets in the management of dyslipidaemias\u2013A report from the European Society of Cardiology Cardiovascular Round Table. J. Clin. Lipidol.","DOI":"10.1016\/j.jacl.2024.07.001"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"17K","DOI":"10.1016\/S0002-9149(03)00774-4","article-title":"High-sensitivity C-reactive protein and cardiovascular risk: Rationale for screening and primary prevention","volume":"92","author":"Ridker","year":"2003","journal-title":"Am. J. Cardiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41572-019-0106-z","article-title":"Atherosclerosis","volume":"5","author":"Libby","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Emerging Risk Factors Collaboration, Kaptoge, S., Di Angelantonio, E., Lowe, G., Pepys, M.B., Thompson, S.G., Collins, R., and Danesh, J. (2010). C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: An individual participant meta-analysis. Lancet, 375, 132\u2013140.","DOI":"10.1016\/S0140-6736(09)61717-7"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1161\/CIRCULATIONAHA.118.034032","article-title":"Inflammatory and Cholesterol Risk in the FOURIER Trial","volume":"138","author":"Bohula","year":"2018","journal-title":"Circulation"},{"key":"ref_105","first-page":"e596","article-title":"2019 ACC\/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"140","author":"Arnett","year":"2019","journal-title":"Circulation"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4109","DOI":"10.1093\/eurheartj\/ehy723","article-title":"Has the time finally come to measure hsCRP universally in primary and secondary cardiovascular prevention?","volume":"39","author":"Ridker","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1056\/NEJMoa0807646","article-title":"Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein","volume":"359","author":"Ridker","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1111\/dom.14081","article-title":"Prevalence of residual inflammatory risk and associated clinical variables in patients with type 2 diabetes","volume":"22","author":"Prattichizzo","year":"2020","journal-title":"Diabetes Obes. Metab."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cyto.2019.02.005","article-title":"C-reactive protein for predicting cardiovascular and all-cause mortality in type 2 diabetic patients: A meta-analysis","volume":"117","author":"Tian","year":"2019","journal-title":"Cytokine"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s12933-021-01409-0","article-title":"SMART study group. Low-grade inflammation as a risk factor for cardiovascular events and all-cause mortality in patients with type 2 diabetes","volume":"20","author":"Sharif","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/eurheartj\/ehaa099","article-title":"Targeting cardiovascular inflammation: Next steps in clinical translation","volume":"42","author":"Lawler","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1210\/jc.2008-2260","article-title":"Association of serum C-reactive protein level with sex-specific type 2 diabetes risk: A prospective finnish study","volume":"94","author":"Hu","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1111\/dom.15514","article-title":"Low-grade inflammation in persons with recently diagnosed type 2 diabetes: The role of abdominal adiposity and putative mediators","volume":"26","author":"Domazet","year":"2024","journal-title":"Diabetes Obes. Metab."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1177\/2047487319885458","article-title":"Modifiable lifestyle risk factors and C-reactive protein in patients with coronary artery disease: Implications for an anti-inflammatory treatment target population","volume":"28","author":"Blaum","year":"2021","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e012174","DOI":"10.1161\/CIRCIMAGING.120.012174","article-title":"Effect of Liraglutide on Arterial Inflammation Assessed as [18F]FDG Uptake in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"14","author":"Ripa","year":"2021","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"108368","DOI":"10.1016\/j.diabres.2020.108368","article-title":"A systematic review examining the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on biomarkers of inflammation and oxidative stress","volume":"168","author":"Bray","year":"2020","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1810327","DOI":"10.1155\/2016\/1810327","article-title":"\u201cInflammaging\u201d as a Druggable Target: A Senescence-Associated Secretory Phenotype-Centered View of Type 2 Diabetes","volume":"2016","author":"Prattichizzo","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"154799","DOI":"10.1016\/j.metabol.2021.154799","article-title":"Diabetes and kidney disease: Emphasis on treatment with SGLT-2 inhibitors and GLP-1 receptor agonists","volume":"120","author":"Prattichizzo","year":"2021","journal-title":"Metabolism"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"154308","DOI":"10.1016\/j.metabol.2020.154308","article-title":"Legacy effect of intensive glucose control on major adverse cardiovascular outcome: Systematic review and meta-analyses of trials according to different scenarios","volume":"110","author":"Prattichizzo","year":"2020","journal-title":"Metabolism"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"D\u2019Onofrio, N., Prattichizzo, F., Martino, E., Anastasio, C., Mele, L., La Grotta, R., Sardu, C., Ceriello, A., Marfella, R., and Paolisso, G. (2023). MiR-27b attenuates mitochondrial oxidative stress and inflammation in endothelial cells. Redox Biol., 62.","DOI":"10.1016\/j.redox.2023.102681"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.18632\/aging.101591","article-title":"The mitomiR\/Bcl-2 axis affects mitochondrial function and autophagic vacuole formation in senescent endothelial cells","volume":"10","author":"Giuliani","year":"2018","journal-title":"Aging"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2309034","DOI":"10.1155\/2017\/2309034","article-title":"Mitochondrial (Dys) Function in Inflammaging: Do MitomiRs Influence the Energetic, Oxidative, and Inflammatory Status of Senescent Cells?","volume":"2017","author":"Giuliani","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"240","DOI":"10.2337\/db20-0199","article-title":"CD31+ Extracellular Vesicles from Patients with Type 2 Diabetes Shuttle a miRNA Signature Associated with Cardiovascular Complications","volume":"70","author":"Prattichizzo","year":"2021","journal-title":"Diabetes"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.7150\/thno.51605","article-title":"Extracellular vesicle-shuttled miRNAs: A critical appraisal of their potential as nano-diagnostics and nano-therapeutics in type 2 diabetes mellitus and its cardiovascular complications","volume":"11","author":"Prattichizzo","year":"2021","journal-title":"Theranostics"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Murakami, T., Inagaki, N., and Kondoh, H. (2022). Cellular Senescence in Diabetes Mellitus: Distinct Senotherapeutic Strategies for Adipose Tissue and Pancreatic \u03b2 Cells. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.869414"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/cei.13344","article-title":"Type 2 diabetes is associated with the accumulation of senescent T cells","volume":"197","author":"Lau","year":"2019","journal-title":"Clin. Exp. Immunol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s41574-020-0335-y","article-title":"The role of cellular senescence in ageing and endocrine disease","volume":"16","author":"Khosla","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"328","DOI":"10.2337\/dbi20-0030","article-title":"Epigenetic Mechanisms in Diabetic Vascular Complications and Metabolic Memory: The 2020 Edwin Bierman Award Lecture","volume":"70","author":"Natarajan","year":"2021","journal-title":"Diabetes"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1161\/CIRCULATIONAHA.120.046464","article-title":"Hyperglycemia Induces Trained Immunity in Macrophages and Their Precursors and Promotes Atherosclerosis","volume":"144","author":"Edgar","year":"2021","journal-title":"Circulation"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"807","DOI":"10.4049\/jimmunol.1901348","article-title":"Hyperglycemic Memory of Innate Immune Cells Promotes In Vitro Proinflammatory Responses of Human Monocytes and Murine Macrophages","volume":"206","author":"Thiem","year":"2021","journal-title":"J. Immunol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mad.2014.11.001","article-title":"Circulating miR-21, miR-146a and Fas ligand respond to postmenopausal estrogen-based hormone replacement therapy\u2014A study with monozygotic twin pairs","volume":"143\u2013144","author":"Kangas","year":"2014","journal-title":"Mech. Ageing Dev."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e23231","DOI":"10.1096\/fj.202301078R","article-title":"Trained immunity in diabetes and hyperlipidemia: Emerging opportunities to target cardiovascular complications and design new therapies","volume":"37","author":"Robinson","year":"2023","journal-title":"FASEB J."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.cell.2017.12.013","article-title":"Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming","volume":"172","author":"Christ","year":"2018","journal-title":"Cell"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.cell.2017.11.034","article-title":"Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity","volume":"172","author":"Mitroulis","year":"2018","journal-title":"Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pharmthera.2018.08.012","article-title":"Interactions between dyslipidemia and the immune system and their relevance as putative therapeutic targets in atherosclerosis","volume":"193","author":"Lacy","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Franceschi, C., Garagnani, P., Morsiani, C., Conte, M., Santoro, A., Grignolio, A., Monti, D., Capri, M., and Salvioli, S. (2018). The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates. Front. Med., 5.","DOI":"10.3389\/fmed.2018.00061"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.exger.2016.02.013","article-title":"Aging and adipose tissue: Potential interventions for diabetes and regenerative medicine","volume":"86","author":"Palmer","year":"2016","journal-title":"Exp. Gerontol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s43587-022-00250-8","article-title":"Characterization of cellular senescence in aging skeletal muscle","volume":"2","author":"Zhang","year":"2022","journal-title":"Nat. Aging"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.cmet.2019.05.006","article-title":"Acceleration of \u03b2 Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes","volume":"30","author":"Andle","year":"2019","journal-title":"Cell Metab."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"101558","DOI":"10.1016\/j.molmet.2022.101558","article-title":"Chronic hyperinsulinemia promotes human hepatocyte senescence","volume":"64","author":"Baboota","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"bqab058","DOI":"10.1210\/endocr\/bqab058","article-title":"Senolytics: Potential for Alleviating Diabetes and Its Complications","volume":"162","author":"Palmer","year":"2021","journal-title":"Endocrinology"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1161\/01.RES.0000256837.40544.4a","article-title":"Vascular cell senescence: Contribution to atherosclerosis","volume":"100","author":"Minamino","year":"2007","journal-title":"Circ. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.redox.2017.12.001","article-title":"Short-term sustained hyperglycaemia fosters an archetypal senescence-associated secretory phenotype in endothelial cells and macrophages","volume":"15","author":"Prattichizzo","year":"2018","journal-title":"Redox Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"bqab136","DOI":"10.1210\/endocr\/bqab136","article-title":"Role of Cellular Senescence in Type II Diabetes","volume":"162","author":"Narasimhan","year":"2021","journal-title":"Endocrinology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.bbi.2015.08.024","article-title":"Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans","volume":"51","author":"Carroll","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Tylutka, A., Morawin, B., Gramacki, A., and Zembron-Lacny, A. (2021). Lifestyle exercise attenuates immunosenescence; flow cytometry analysis. BMC Geriatr., 21.","DOI":"10.1186\/s12877-021-02128-7"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Yzydorczyk, C., Li, N., Chehade, H., Mosig, D., Bidho, M., Keshavjee, B., Armengaud, J.B., Nardou, K., Siddeek, B., and Benahmed, M. (2017). Transient postnatal overfeeding causes liver stress-induced premature senescence in adult mice. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-11756-2"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"e14101","DOI":"10.1111\/acel.14101","article-title":"Alterations of the gut microbiome are associated with epigenetic age acceleration and physical fitness","volume":"23","author":"Torma","year":"2024","journal-title":"Aging Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"aaf1098","DOI":"10.1126\/science.aaf1098","article-title":"Trained immunity: A program of innate immune memory in health and disease","volume":"352","author":"Netea","year":"2016","journal-title":"Science"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s11010-012-1276-0","article-title":"Accelerated aging as evidenced by increased telomere shortening and mitochondrial DNA depletion in patients with type 2 diabetes","volume":"365","author":"Monickaraj","year":"2012","journal-title":"Mol. Cell Biochem."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"50835","DOI":"10.18632\/oncotarget.10615","article-title":"Leukocyte telomere length and mortality risk in patients with type 2 diabetes","volume":"7","author":"Bonfigli","year":"2016","journal-title":"Oncotarget"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"102253","DOI":"10.1016\/j.arr.2024.102253","article-title":"Organ-specific biological clocks: Ageotyping for personalized anti-aging medicine","volume":"96","author":"Prattichizzo","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1186\/s12933-024-02351-7","article-title":"DNA Methylation-derived biological age and long-term mortality risk in subjects with type 2 diabetes","volume":"23","author":"Sabbatinelli","year":"2024","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41581-022-00601-z","article-title":"Cellular senescence: The good, the bad and the unknown","volume":"18","author":"Huang","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ebiom.2019.08.069","article-title":"Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease","volume":"47","author":"Hickson","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S2213-8587(21)00203-5","article-title":"Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: A systematic review and meta-analysis of randomised trials","volume":"9","author":"Sattar","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"m4573","DOI":"10.1136\/bmj.m4573","article-title":"Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: Systematic review and network meta-analysis of randomised controlled trials","volume":"372","author":"Palmer","year":"2021","journal-title":"BMJ"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1056\/NEJMoa2306963","article-title":"STEP-HFpEF Trial Committees and Investigators. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity","volume":"389","author":"Kosiborod","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1056\/NEJMoa2313917","article-title":"STEP-HFpEF DM Trial Committees and Investigators. Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes","volume":"390","author":"Kosiborod","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S2213-8587(24)00102-5","article-title":"Effect of SGLT2 inhibitors on heart failure outcomes and cardiovascular death across the cardiometabolic disease spectrum: A systematic review and meta-analysis","volume":"12","author":"Usman","year":"2024","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Marfella, R., Sardu, C., D\u2019Onofrio, N., Fumagalli, C., Scisciola, L., Sasso, F.C., Siniscalchi, M., Marfella, L.V., D\u2019Andrea, D., and Minicucci, F. (2023). SGLT-2 inhibitors and in-stent restenosis-related events after acute myocardial infarction: An observational study in patients with type 2 diabetes. BMC Med., 21.","DOI":"10.1186\/s12916-023-02781-2"},{"key":"ref_162","first-page":"e078242","article-title":"Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: Population based cohort study","volume":"385","author":"Treves","year":"2024","journal-title":"BMJ"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12933-023-02118-6","article-title":"GLP-1 receptor agonists-SGLT-2 inhibitors combination therapy and cardiovascular events after acute myocardial infarction: An observational study in patients with type 2 diabetes","volume":"23","author":"Marfella","year":"2024","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1177\/2047487319880040","article-title":"Glucose-lowering therapies in patients with type 2 diabetes and cardiovascular diseases","volume":"26","author":"Prattichizzo","year":"2019","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12933-021-01281-y","article-title":"From glucose lowering agents to disease\/diabetes modifying drugs: A \u201cSIMPLE\u201d approach for the treatment of type 2 diabetes","volume":"20","author":"Mosenzon","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1007\/s00125-013-3145-0","article-title":"Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus","volume":"57","author":"Hogan","year":"2014","journal-title":"Diabetologia"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.tem.2024.02.003","article-title":"Systemic and organ-specific anti-inflammatory effects of sodium-glucose cotransporter-2 inhibitors","volume":"35","author":"Mashayekhi","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00018-022-04289-z","article-title":"Anti-inflammatory effect of SGLT-2 inhibitors via uric acid and insulin","volume":"79","author":"Olivieri","year":"2022","journal-title":"Cell Mol. Life Sci."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"e30553","DOI":"10.1097\/MD.0000000000030553","article-title":"Meta-analysis of the effect of sodium-dependent glucose transporter 2 inhibitors on C-reactive protein in type 2 diabetes","volume":"101","author":"Sun","year":"2022","journal-title":"Medicine"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1007\/s00125-019-4859-4","article-title":"Canagliflozin reduces inflammation and fibrosis biomarkers: A potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease","volume":"62","author":"Heerspink","year":"2019","journal-title":"Diabetologia"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1007\/s00125-011-2297-z","article-title":"Glucagon-like peptide-1 (GLP-1) receptor agonists, obesity and psoriasis: Diabetes meets dermatology","volume":"54","author":"Drucker","year":"2011","journal-title":"Diabetologia"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"101351","DOI":"10.1016\/j.molmet.2021.101351","article-title":"GLP-1 physiology informs the pharmacotherapy of obesity","volume":"57","author":"Drucker","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.ajcnut.2023.04.017","article-title":"The Weight-loss Effect of GLP-1RAs Glucagon-Like Peptide-1 Receptor Agonists in Non-diabetic Individuals with Overweight or Obesity: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials","volume":"118","author":"Liu","year":"2023","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.2337\/dci21-0034","article-title":"Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes","volume":"44","author":"Riddle","year":"2021","journal-title":"Diabetes Care"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.2337\/dc24-0491","article-title":"Effect of Semaglutide on Regression and Progression of Glycemia in People with Overweight or Obesity but Without Diabetes in the SELECT Trial","volume":"47","author":"Kahn","year":"2024","journal-title":"Diabetes Care"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa2107519","article-title":"SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes","volume":"385","author":"Davies","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1016\/S0140-6736(21)02188-7","article-title":"SURPASS-4 Investigators. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): A randomised, open-label, parallel-group, multicentre, phase 3 trial","volume":"398","author":"Kahn","year":"2021","journal-title":"Lancet"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.2337\/dc23-0872","article-title":"Achieving Normoglycemia with Tirzepatide: Analysis of SURPASS 1-4 Trials","volume":"46","author":"Rosenstock","year":"2023","journal-title":"Diabetes Care"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0531-5565(00)00084-X","article-title":"Caloric restriction and aging: An update","volume":"35","author":"Masoro","year":"2000","journal-title":"Exp. Gerontol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S2213-8587(19)30151-2","article-title":"CALERIE Investigators. 2 years of calorie restriction and cardiometabolic risk (CALERIE): Exploratory outcomes of a multicentre, phase 2, randomised controlled trial","volume":"7","author":"Kraus","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1172\/JCI72227","article-title":"Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients","volume":"124","author":"Ferrannini","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.2337\/dc15-0355","article-title":"Energy Balance After Sodium-Glucose Cotransporter 2 Inhibition","volume":"38","author":"Ferrannini","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"La Grotta, R., Frig\u00e9, C., Matacchione, G., Olivieri, F., de Candia, P., Ceriello, A., and Prattichizzo, F. (2022). Repurposing SGLT-2 Inhibitors to Target Aging: Available Evidence and Molecular Mechanisms. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012325"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"e164296","DOI":"10.1172\/jci.insight.164296","article-title":"Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition","volume":"8","author":"Riahi","year":"2023","journal-title":"JCI Insight"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.pcad.2023.10.003","article-title":"SGLT inhibitors for improving Healthspan and lifespan","volume":"81","author":"Weidling","year":"2023","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/S2213-8587(21)00295-3","article-title":"DAPA-CKD and DAPA-HF Trial Committees and Investigators. Dapagliflozin and new-onset type 2 diabetes in patients with chronic kidney disease or heart failure: Pooled analysis of the DAPA-CKD and DAPA-HF trials","volume":"10","author":"Rossing","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"100666","DOI":"10.1016\/j.lanepe.2023.100666","article-title":"AMD Annals study group. The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: A cohort study with newly-diagnosed people with type 2 diabetes","volume":"31","author":"Ceriello","year":"2023","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/S2213-8587(21)00022-X","article-title":"Positioning newer drugs in the management of type 2 diabetes","volume":"9","author":"Prattichizzo","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41574-019-0294-3","article-title":"Two drugs are better than one to start T2DM therapy","volume":"16","author":"Prattichizzo","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"467","DOI":"10.2337\/dc23-1825","article-title":"Low-Dose Colchicine in Patients with Type 2 Diabetes and Recent Myocardial Infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)","volume":"47","author":"Roubille","year":"2024","journal-title":"Diabetes Care"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1016\/S0140-6736(21)00520-1","article-title":"IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): A double-blind, randomised, placebo-controlled, phase 2 trial","volume":"397","author":"Ridker","year":"2021","journal-title":"Lancet"},{"key":"ref_192","unstructured":"(2024, August 01). Available online: https:\/\/www.sec.gov\/Archives\/edgar\/data\/1114448\/000137036818000045\/a181018-99_1.htm."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.jacc.2023.05.055","article-title":"Low-Dose Colchicine for Secondary Prevention of Coronary Artery Disease: JACC Review Topic of the Week","volume":"82","author":"Nelson","year":"2023","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/19\/1662\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:09:20Z","timestamp":1760112560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/19\/1662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,8]]},"references-count":193,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["cells13191662"],"URL":"https:\/\/doi.org\/10.3390\/cells13191662","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,8]]}}}