{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T15:35:16Z","timestamp":1764084916629,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RF-2018-12365985"],"award-info":[{"award-number":["RF-2018-12365985"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chitotriosidase (CHIT), a mammalian chitinase secreted by neutrophils and activated macrophages, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. The aim of this study is to evaluate CHIT activity as an early biomarker of arterial stiffness in people with T2D free from overt vascular complications. In this cross-sectional study, arterial stiffness as measured using standard pulse wave velocity (PWV) was evaluated in 174 people with T2D without overt vascular disease. Then, we measured CHIT serum activity with an electrochemiluminescence assay in two subgroups of participants: 35 with the highest (high-PWV) and 40 with the lowest (low-PWV) PWV values. CHIT activity was no different between the low-PVW and high-PWV groups (12.7 [9.6\u201317.9] vs. 11.4 [8.8\u201315.0] nmol\/mL\/h, respectively). Compared with the low-PWV group, the high-PWV participants were older (p &lt; 0.001); had a longer duration of diabetes (p = 0.03); higher ankle\u2013brachial index ABI (p = 0.04), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.005), fasting blood glucose (p = 0.008), and HbA1c (p = 0.005); and lower eGFR (p = 0.03) and body mass index (BMI) (p = 0.01). No association was present with sex, duration of diabetes, age, BMI, peripheral blood pressure, laboratory parameters, and glucose-lowering medications or ongoing antihypertensive therapy. Although no association was found, this study provides novel data about the association of CHIT activity with CVD, focusing on a specific outcome (arterial stiffness) in a well-defined population of subjects with T2D without established CVD.<\/jats:p>","DOI":"10.3390\/ijms242115809","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T11:16:27Z","timestamp":1698750987000},"page":"15809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lack of Association between Serum Chitotriosidase Activity and Arterial Stiffness in Type 2 Diabetes without Cardiovascular Complications"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3905-0139","authenticated-orcid":false,"given":"Luca","family":"D\u2019Onofrio","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, \u201cSapienza\u201d University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8740-0549","authenticated-orcid":false,"given":"Rocco","family":"Amendolara","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, \u201cSapienza\u201d University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Mignogna","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, \u201cSapienza\u201d University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaetano","family":"Leto","sequence":"additional","affiliation":[{"name":"Diabetes Unit, Department of Medical-Surgical Sciences and Biotechnologies, Santa Maria Goretti Hospital, Sapienza University of Rome, 04100 Latina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lida","family":"Tartaglione","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3071-1893","authenticated-orcid":false,"given":"Sandro","family":"Mazzaferro","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3844-9463","authenticated-orcid":false,"given":"Ernesto","family":"Maddaloni","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, \u201cSapienza\u201d University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1490-6041","authenticated-orcid":false,"given":"Raffaella","family":"Buzzetti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, \u201cSapienza\u201d University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1016\/S0140-6736(22)01655-5","article-title":"Type 2 diabetes","volume":"400","author":"Ahmad","year":"2022","journal-title":"Lancet"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12933-018-0787-8","article-title":"Vascular complications in patients with type 2 diabetes: Prevalence and associated factors in 38 countries (the DISCOVER study program)","volume":"17","author":"Kosiborod","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.cjca.2017.12.005","article-title":"Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms","volume":"34","author":"Petrie","year":"2018","journal-title":"Can. J. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s11739-011-0678-4","article-title":"Aortic stiffness, blood pressure and renal dysfunction","volume":"6","author":"Grassi","year":"2011","journal-title":"Intern. Emerg. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1161\/HYPERTENSIONAHA.122.19256","article-title":"Hypertension, Arterial Stiffness, and Diabetes: A Prospective Cohort Study","volume":"79","author":"Tian","year":"2022","journal-title":"Hypertens"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.2337\/dc13-1886","article-title":"Brachial-ankle pulse wave velocity predicts all-cause mortality and cardiovascular events in patients with diabetes: The Kyushu Prevention Study of Atherosclerosis","volume":"37","author":"Maeda","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1007\/s00125-012-2517-1","article-title":"Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients through endothelial dysfunction","volume":"55","author":"Bruno","year":"2012","journal-title":"Diabetologia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8979","DOI":"10.1073\/pnas.151103798","article-title":"Structural insights into the catalytic mechanism of a family 18 exo-chitinase","volume":"98","author":"Komander","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"doi-asserted-by":"crossref","unstructured":"Zurawska-P\u0142aksej, E., \u0141ugowska, A., Hetma\u00f1czyk, K., Knapik-Kordecka, M., and Piwowar, A. (2015). Neutrophils as a Source of Chitinases and Chitinase-Like Proteins in Type 2 Diabetes. PLoS ONE, 10.","key":"ref_10","DOI":"10.1371\/journal.pone.0141730"},{"doi-asserted-by":"crossref","unstructured":"Kuusk, S., S\u00f8rlie, M., and V\u00e4ljam\u00e4e, P. (2017). Human Chitotriosidase Is an Endo-Processive Enzyme. PLoS ONE, 12.","key":"ref_11","DOI":"10.1371\/journal.pone.0171042"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s00198-015-3254-3","article-title":"Serum chitotriosidase in postmenopausal women with severe osteoporosis","volume":"27","author":"Musumeci","year":"2016","journal-title":"Osteoporos. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1111\/j.1572-0241.2006.00680.x","article-title":"Potential role of chitotriosidase gene in nonalcoholic fatty liver disease evolution","volume":"101","author":"Malaguarnera","year":"2006","journal-title":"Am. J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1161\/01.ATV.0000089329.09061.07","article-title":"Serum chitotriosidase activity is increased in subjects with atherosclerosis disease","volume":"23","author":"Artieda","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S503","DOI":"10.1016\/j.dsx.2017.03.044","article-title":"Serum chitotriosidase enzyme activity is closely related to HbA1c levels and the complications in patients with diabetes mellitus type 2","volume":"11","author":"Turan","year":"2017","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107686","DOI":"10.1016\/j.jdiacomp.2020.107686","article-title":"The changing features of serum adropin, copeptin, neprilysin and chitotriosidase which are associated with vascular endothelial function in type 2 diabetic retinopathy patients","volume":"34","author":"Li","year":"2020","journal-title":"J. Diabetes Complicat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s12020-010-9334-4","article-title":"Chitotriosidase activity predicts endothelial dysfunction in type-2 diabetes mellitus","volume":"37","author":"Sonmez","year":"2010","journal-title":"Endocrine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.atherosclerosis.2014.12.023","article-title":"Arterial stiffness in diabetes mellitus","volume":"238","author":"Prenner","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S0002-9149(02)02593-6","article-title":"Comparison of carotid intima-media thickness, arterial stiffness, and brachial artery flow mediated dilatation in diabetic and nondiabetic subjects (The Chennai Urban Population Study [CUPS-9])","volume":"90","author":"Ravikumar","year":"2002","journal-title":"Am. J. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e3134","DOI":"10.1002\/dmrr.3134","article-title":"Risk factors and predictive biomarkers of early cardiovascular disease in obese youth","volume":"35","author":"Ho","year":"2019","journal-title":"Diabetes. Metab. Res. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e3632","DOI":"10.1002\/dmrr.3632","article-title":"Association of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease and retinopathy in type 2 diabetes","volume":"39","author":"Maddaloni","year":"2023","journal-title":"Diabetes. Metab. Res. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e3217","DOI":"10.1002\/dmrr.3217","article-title":"Osteocalcin and sclerostin: Background characters or main actors in cardiovascular disease?","volume":"36","author":"Maddaloni","year":"2020","journal-title":"Diabetes. Metab. Res. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.clinbiochem.2017.12.010","article-title":"Association of vascular indices with novel circulating biomarkers as prognostic factors for cardiovascular complications in patients with type 2 diabetes mellitus","volume":"53","author":"Naka","year":"2018","journal-title":"Clin. Biochem."},{"key":"ref_24","first-page":"183","article-title":"The relationship between serum YKL-40 levels and arterial stiffness in patients with ankylosing spondylitis","volume":"42","author":"Devrimsel","year":"2017","journal-title":"Acta Reumatol. Port."},{"doi-asserted-by":"crossref","unstructured":"Ma, W.H., Wang, X.L., Du, Y.M., Wang, Y.B., Zhang, Y., Wei, D.E., Guo, L.L., and Bu, P.L. (2012). Association between human cartilage glycoprotein 39 (YKL-40) and arterial stiffness in essential hypertension. BMC Cardiovasc. Disord., 12.","key":"ref_25","DOI":"10.1186\/1471-2261-12-35"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1007\/s00296-013-2810-4","article-title":"Relationship between pulse wave velocity and serum YKL-40 level in patients with early rheumatoid arthritis","volume":"33","author":"Turkyilmaz","year":"2013","journal-title":"Rheumatol. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1196\/annals.1395.017","article-title":"Chitotriosidase levels in healthy elderly subjects","volume":"1100","author":"Kurt","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"25680","DOI":"10.1074\/jbc.273.40.25680","article-title":"The human chitotriosidase gene. Nature of inherited enzyme deficiency","volume":"273","author":"Boot","year":"1998","journal-title":"J. Biol. Chem."},{"doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2014). Standards of medical care in diabetes\u20142014. Diabetes Care, 37, S14\u2013S80.","key":"ref_29","DOI":"10.2337\/dc14-S014"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101","DOI":"10.5551\/jat.13.101","article-title":"A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI)","volume":"13","author":"Shirai","year":"2006","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin. Chem."},{"key":"ref_32","first-page":"604","article-title":"A New equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"FMC Form. Medica Contin. Aten. Primaria"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1172\/JCI117084","article-title":"Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease","volume":"93","author":"Hollak","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"E3857","DOI":"10.1210\/clinem\/dgac291","article-title":"Diastolic Pressure and ACR Are Modifiable Risk Factors of Arterial Stiffness in T2DM Without Cardiovascular Disease","volume":"107","author":"Leto","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/15809\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:14:50Z","timestamp":1760130890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/15809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":34,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242115809"],"URL":"https:\/\/doi.org\/10.3390\/ijms242115809","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,10,31]]}}}