{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T14:00:25Z","timestamp":1784210425712,"version":"3.55.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,4,21]],"date-time":"2016-04-21T00:00:00Z","timestamp":1461196800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2016,4]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Chronic inflammation promotes atherosclerosis and is a prognostic factor in coronary artery disease (CAD<\/jats:styled-content>). Patients with type 2 diabetes mellitus (DM2<\/jats:styled-content>) are at risk for progressive atherosclerosis. Macrophage migration inhibitory factor (MIF<\/jats:styled-content>) is a key player in atherosclerosis, mediating pro\u2010inflammatory responses. Its endogenous antagonist Gremlin\u20101 inhibits foam\u2010cell formation and atheroprogression by binding MIF<\/jats:styled-content>, neutralizing its proatherosclerotic functions.<\/jats:p><\/jats:sec>Hypothesis<\/jats:title>Plasma levels of MIF<\/jats:styled-content> and Gremlin\u20101 correlate with the stability of CAD<\/jats:styled-content> in patients with DM2<\/jats:styled-content>.<\/jats:p><\/jats:sec>Method<\/jats:title>We assessed plasma levels of Gremlin\u20101 and MIF<\/jats:styled-content> in 198 nondiabetic and 88 diabetic patients with symptomatic CAD<\/jats:styled-content> using enzyme\u2010linked immunosorbent assays.<\/jats:p><\/jats:sec>Results<\/jats:title>Plasma levels of Gremlin\u20101 were higher DM2<\/jats:styled-content> patients (278.8 \u00b1 16.6 vs 224.7 \u00b1 6.7 ng\/mL<\/jats:styled-content>; P<\/jats:italic> = 0.001). MIF<\/jats:styled-content> levels were elevated but not significantly increased in DM2<\/jats:styled-content> (P<\/jats:italic> = 0.098). Interestingly, we found that Gremlin\u20101 plasma levels were significantly higher in diabetic patients with stable angina pectoris (SAP<\/jats:styled-content>; n = 53) or acute coronary syndrome (ACS<\/jats:styled-content>; n = 35) compared with nondiabetic patients with SAP<\/jats:styled-content> (P<\/jats:italic> = 0.008 and P<\/jats:italic> = 0.011, respectively). MIF<\/jats:styled-content> levels were significantly higher in diabetic patients with ACS<\/jats:styled-content> compared with SAP<\/jats:styled-content> (P<\/jats:italic> < 0.001). Although the single plasma parameters showed an association with DM2<\/jats:styled-content> and CAD<\/jats:styled-content> status, we could not confirm that the Gremlin\u20101\/MIF<\/jats:styled-content> ratio is significantly different in patients stratified by DM2<\/jats:styled-content> and CAD<\/jats:styled-content> (P<\/jats:italic> = 0.072). Hence, Gremlin\u20101\/MIF<\/jats:styled-content> ratio was significantly lower in patients with ACS<\/jats:styled-content> compared with SAP<\/jats:styled-content> (1.1 \u00b1 0.1 vs 4.4 \u00b1 1.1; P<\/jats:italic> = 0.003).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Diabetic patients with ACS<\/jats:styled-content> show increased levels of Gremlin\u20101 and MIF<\/jats:styled-content>, leading to unfavorable Gremlin\u20101\/MIF<\/jats:styled-content> ratios. However, DM2<\/jats:styled-content> alone is not associated with low Gremlin\u20101\/MIF<\/jats:styled-content> ratios.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clc.22509","type":"journal-article","created":{"date-parts":[[2016,4,21]],"date-time":"2016-04-21T17:32:26Z","timestamp":1461259946000},"page":"201-206","source":"Crossref","is-referenced-by-count":16,"title":["High Plasma Levels of Gremlin\u20101 and Macrophage Migration Inhibitory Factor, but Not Their Ratio, Indicate an Increased Risk for Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus"],"prefix":"10.1002","volume":"39","author":[{"given":"Karin A.L.","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Department of Cardiology and Circulatory Diseases, Internal Medicine Clinic III Eberhard Karls University T\u00fcbingen T\u00fcbingen Germany"},{"name":"La Jolla Institute for Allergy and Immunology La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Circulatory Diseases, Internal Medicine Clinic III Eberhard Karls University T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Schmid","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Circulatory Diseases, Internal Medicine Clinic III Eberhard Karls University T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Schoenleber","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Circulatory Diseases, Internal Medicine Clinic III Eberhard Karls University T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meinrad","family":"Gawaz","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Circulatory Diseases, Internal Medicine Clinic III Eberhard Karls University T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Geisler","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Circulatory Diseases, Internal Medicine Clinic III Eberhard Karls University T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris I.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Circulatory Diseases, Internal Medicine Clinic III Eberhard Karls University T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35025203"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(99)70266-8"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.1.110304.100100"},{"key":"e_1_2_7_5_1","first-page":"RA308","article-title":"The role of inflammation in atherothrombosis: current and future strategies of medical treatment","volume":"10","author":"Geisler T","year":"2004","journal-title":"Med Sci 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