{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T23:50:38Z","timestamp":1783295438443,"version":"3.54.6"},"reference-count":51,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan","award":["TCRD109-71"],"award-info":[{"award-number":["TCRD109-71"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>The adipocyte fatty-acid binding protein (A-FABP) is predominantly expressed in macrophages and adipocytes and is an essential mediator of inflammation and atherosclerosis pathogenesis. Atherosclerosis is an aggravating factor for peripheral arterial disease (PAD). Our study intended to study the association between PAD and serum A-FABP levels in type-2 diabetes mellitus (T2DM) patients. One hundred and twenty T2DM subjects were enrolled in the study. Fasting blood samples were collected to determine biochemical data and A-FABP levels. By the automatic oscillometric method, the ankle\u2013brachial index (ABI) was measured. Low ABI was defined as any value &lt; 0.9. Twenty participants with T2DM (16.7%) were included in the low ABI group. Low ABI T2DM participants had an increased mean body mass index, body fat mass, systolic blood pressure, C-reactive protein, urine albumin\u2013creatinine ratio, and A-FABP levels compared to those in the normal ABI group. After variables significantly associated with PAD were adjusted by multivariate logistic regression analyses, circulating A-FABP levels (odds ratio [OR]: 1.138; 95 percent confidence interval [CI]: 1.023\u20131.266; p = 0.017) were identified as the independent marker of PAD. In conclusion, fasting serum A-FABP value has positive association with PAD in T2DM patients.<\/jats:p>","DOI":"10.3390\/ijerph19159459","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T21:41:37Z","timestamp":1659476497000},"page":"9459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Serum Adipocyte Fatty-Acid Binding Protein as an Independent Marker of Peripheral Artery Disease in Patients with Type-2 Diabetes Mellitus"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-4558","authenticated-orcid":false,"given":"Bang-Gee","family":"Hsu","sequence":"first","affiliation":[{"name":"Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Yee","family":"Mah","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du-An","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Division of Metabolism and Endocrinology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0910-1185","authenticated-orcid":false,"given":"Ming-Chun","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Department of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00125-018-4711-2","article-title":"Global trends in diabetes complications: A review of current evidence","volume":"62","author":"Harding","year":"2019","journal-title":"Diabetologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa1008862","article-title":"Diabetes mellitus, fasting glucose, and risk of cause-specific death","volume":"364","author":"Kaptoge","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11886-019-1107-y","article-title":"Epidemiology of diabetes mellitus and cardiovascular disease","volume":"21","author":"Glovaci","year":"2019","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1001\/jama.300.2.197","article-title":"Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: A meta-analysis","volume":"300","author":"Fowkes","year":"2008","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"572","DOI":"10.23736\/S0021-9509.18.10405-8","article-title":"Peripheral arterial disease in diabetic patients: A long-term population-based study on occurrence, outcomes and cost","volume":"59","author":"Marone","year":"2018","journal-title":"J. Cardiovasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"870","DOI":"10.3390\/jcm8060870","article-title":"Role of low ankle-brachial index in cardiovascular and mortality risk compared with major risk conditions","volume":"8","author":"Lia","year":"2019","journal-title":"J. Clin. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11970","DOI":"10.3390\/ijerph182211970","article-title":"Pathogenesis and clinical significance of in-stent restenosis in patients with diabetes","volume":"18","author":"Grzegorz","year":"2021","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1177\/1479164109336043","article-title":"Prevalence and risk factors for peripheral artery disease in an Asian population with diabetes mellitus","volume":"6","author":"Tavintharan","year":"2009","journal-title":"Diab. Vasc. Dis. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1161\/CIRCRESAHA.116.303849","article-title":"Epidemiology of peripheral artery disease","volume":"116","author":"Criqui","year":"2015","journal-title":"Circ. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"961","DOI":"10.4239\/wjd.v6.i7.961","article-title":"Peripheral artery disease in patients with diabetes: Epidemiology, mechanisms, and outcomes","volume":"6","author":"Thejasvi","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.2337\/diacare.27.12.2843","article-title":"Peripheral arterial disease, diabetes, and mortality","volume":"27","author":"Leibson","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9339","DOI":"10.3390\/ijerph17249339","article-title":"Chronic Lower extremity ischemia and its association with the frailty syndrome in patients with diabetes","volume":"17","author":"Grzegorz","year":"2020","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.cca.2017.08.030","article-title":"High serum adipocyte fatty acid binding protein level as a potential biomarker of aortic arterial stiffness in hypertensive patients with metabolic syndrome","volume":"473","author":"Chen","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_14","first-page":"23","article-title":"Fatty acid-binding protein 4 (FABP4): Pathophysiological insights and potent clinical biomarker of metabolic and cardiovascular diseases","volume":"8","author":"Furuhashi","year":"2014","journal-title":"Clin. Med. Insights Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1161\/01.ATV.0000033090.81345.E6","article-title":"Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia","volume":"22","author":"Boord","year":"2002","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/89076","article-title":"Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis","volume":"7","author":"Makowski","year":"2001","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1161\/ATVBAHA.112.248609","article-title":"Circulating adipocyte fatty acid-binding protein levels and cardiovascular morbidity and mortality in patients with coronary heart disease: A 10-year prospective study","volume":"32","author":"Breitling","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/1753-0407.12474","article-title":"Pathophysiology of peripheral arterial disease in diabetes mellitus","volume":"9","author":"Yang","year":"2017","journal-title":"J. Diabetes"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"875","DOI":"10.4093\/dmj.2019.0221","article-title":"Serum levels of adipocyte fatty acid-binding protein are associated with rapid renal function decline in patients with type 2 diabetes mellitus and preserved renal function","volume":"44","author":"Seo","year":"2020","journal-title":"Diabetes Metab. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s10157-017-1438-1","article-title":"Serum adipocyte fatty acid-binding protein level is associated with arterial stiffness quantified with cardio-ankle vascular index in kidney transplant patients","volume":"22","author":"Chen","year":"2018","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/1744-9987.13431","article-title":"Positive association of serum adipocyte fatty acid binding protein level with peripheral artery disease in hemodialysis patients","volume":"24","author":"Lai","year":"2020","journal-title":"Ther. Apher. Dial."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8380279","DOI":"10.1155\/2016\/8380279","article-title":"High serum adipocyte fatty acid binding protein is associated with metabolic syndrome in patients with type 2 diabetes","volume":"2016","author":"Li","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hsu, B.G., Lee, C.J., Yang, C.F., Chen, Y.C., and Wang, J.H. (2017). High serum resistin levels are associated with peripheral artery disease in the hypertensive patients. BMC Cardiovasc. Disord., 17.","DOI":"10.1186\/s12872-017-0517-2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3109\/07853890903521070","article-title":"A review of simple, non-invasive means of assessing peripheral arterial disease and implications for medical management","volume":"42","author":"Ferreira","year":"2010","journal-title":"Ann. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/S0140-6736(13)61249-0","article-title":"Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: A systematic review and analysis","volume":"382","author":"Fowkes","year":"2013","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1177\/1358836X0100600402","article-title":"Small and large artery elasticity indices in peripheral arterial occlusive disease (PAOD)","volume":"6","author":"Duprez","year":"2001","journal-title":"Vasc. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4103\/tcmj.tcmj_19_19","article-title":"Negative correlation of serum adiponectin level with peripheral artery occlusive disease in hemodialysis patients","volume":"32","author":"Lai","year":"2020","journal-title":"Tzu Chi Med. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.jvs.2006.12.037","article-title":"Inter-society consensus for the management of peripheral arterial disease (TASC II)","volume":"45","author":"Norgren","year":"2007","journal-title":"J. Vasc. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/S2213-8587(17)30183-3","article-title":"Measures of chronic kidney disease and risk of incident peripheral artery disease: A collaborative meta-analysis of individual participant data","volume":"5","author":"Matsushita","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1161\/01.CIR.96.1.44","article-title":"Intermittent claudication. A risk profile from The Framingham Heart Study","volume":"96","author":"Murabito","year":"1997","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hung, P.H., Tsai, H.B., Lin, C.H., and Hung, K.Y. (2013). Abdominal obesity is associated with peripheral artery disease in hemodialysis patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067555"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00392-009-0754-1","article-title":"Risk factor profile, management and prognosis of patients with peripheral arterial disease with or without coronary artery disease: Results of the prospective German REACH registry cohort","volume":"98","author":"Zeymer","year":"2009","journal-title":"Clin. Res. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"161","DOI":"10.14740\/cr508e","article-title":"Pulse pressure and upstroke time are useful parameters for the diagnosis of peripheral artery disease in patients with normal ankle brachial index","volume":"7","author":"Kiuchi","year":"2016","journal-title":"Cardiol. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1007\/s10439-011-0443-x","article-title":"Systolic hypertension mechanisms: Effect of global and local proximal aorta stiffening on pulse pressure","volume":"40","author":"Reymond","year":"2012","journal-title":"Ann. Biomed. Eng."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1161\/01.CIR.0000128520.37674.EF","article-title":"Atherosclerotic vascular disease conference: Writing group III: Pathophysiology","volume":"109","author":"Faxon","year":"2004","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1093\/eurheartj\/ehq387","article-title":"Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events","volume":"32","author":"Peeters","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.numecd.2010.09.008","article-title":"The role of serum adipocyte fatty acid-binding protein on the development of metabolic syndrome is independent of pro-inflammatory cytokines","volume":"22","author":"Park","year":"2012","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.ahj.2013.02.024","article-title":"Gender differences in clinical outcomes among diabetic patients hospitalized for cardiovascular disease","volume":"165","author":"Flink","year":"2013","journal-title":"Am. Heart J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"94","DOI":"10.5603\/KP.a2014.0152","article-title":"Adipocyte fatty acid binding protein levels in patients with coronary artery disease and its relationship to alternative biomarkers","volume":"73","author":"Kaman","year":"2015","journal-title":"Kardiol. Pol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/nature05844","article-title":"Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2","volume":"447","author":"Furuhashi","year":"2007","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1177\/0003319717728226","article-title":"FABP4 and cardiovascular events in peripheral arterial disease","volume":"69","author":"Herz","year":"2018","journal-title":"Angiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrd2589","article-title":"Fatty acid-binding proteins: Role in metabolic diseases and potential as drug targets","volume":"7","author":"Furuhashi","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.atherosclerosis.2010.01.032","article-title":"Serum adipocyte fatty acid-binding protein is independently associated with coronary atherosclerotic burden measured by intravascular ultrasound","volume":"211","author":"Miyoshi","year":"2010","journal-title":"Atherosclerosis"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1161\/ATVBAHA.107.146274","article-title":"Serum adipocyte fatty acid-binding protein levels were independently associated with carotid atherosclerosis","volume":"27","author":"Yeung","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bao, Y., Lu, Z., Zhou, M., Li, H., Wang, Y., Gao, M., Wei, M., and Jia, W. (2011). Serum levels of adipocyte fatty acid-binding protein are associated with the severity of coronary artery disease in Chinese women. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019115"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/1753-0407.12549","article-title":"Serum adipocyte fatty acid-binding protein levels are associated with peripheral arterial disease in women, but not men, with type 2 diabetes mellitus","volume":"10","author":"Ding","year":"2018","journal-title":"J. Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1093\/ajh\/hpv189","article-title":"Smoking behaviors and arterial stiffness measured by pulse wave velocity in older adults: The Atherosclerosis Risk in Communities (ARIC) study","volume":"29","author":"Camplain","year":"2016","journal-title":"Am. J. Hypertens."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"j909","DOI":"10.1136\/bmj.j909","article-title":"Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: Population based cohort study using linked health records","volume":"356","author":"Bell","year":"2017","journal-title":"BMJ"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1232583","DOI":"10.1155\/2018\/1232583","article-title":"Effects of newer antidiabetic drugs on endothelial function and arterial stiffness: A systematic review and meta-analysis","volume":"2018","author":"Batzias","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.ijcard.2016.11.073","article-title":"Effects of statin therapy on arterial stiffness: A systematic review and meta-analysis of randomized controlled trial","volume":"227","author":"Upala","year":"2017","journal-title":"Int. J. Cardiol."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/15\/9459\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:01:07Z","timestamp":1760140867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/15\/9459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,2]]},"references-count":51,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijerph19159459"],"URL":"https:\/\/doi.org\/10.3390\/ijerph19159459","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,2]]}}}