{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:05:10Z","timestamp":1791925510250,"version":"4.3.4"},"reference-count":62,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":2638,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,7,1]]},"abstract":"<jats:sec><jats:title>OBJECTIVE<\/jats:title><jats:p>Immune dysregulation can affect insulin resistance (IR) and \u03b2-cell function and hence contribute to development of type 2 diabetes mellitus (T2DM). The complement system, as a regulator of immune and inflammatory homeostasis, may be a relevant contributor therein. However, longitudinal studies focusing on complement as a determinant of T2DM and IR are scarce. Therefore, we prospectively investigated the association of plasma complement factor 3 (C3) with (estimates of) IR in muscle, liver, and adipocytes, as well as with glucose tolerance, including incident T2DM.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESEARCH DESIGN AND METHODS<\/jats:title><jats:p>Fasting C3, nonesterified fatty acids, glucose, and insulin (the latter two during oral glucose tolerance tests) were measured at baseline (n = 545) and after 7 years of follow-up (n = 394) in a prospective cohort study.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Over the 7-year period, C3 levels (per 0.1 g\/L) were longitudinally associated with higher homeostasis model assessment of IR (HOMA2-IR; \u03b2 = 15.2% [95% CI 12.9\u201317.6]), hepatic IR (\u03b2 = 6.1% [95% CI 4.7\u20137.4]), adipocyte IR (\u03b2 = 16.0% [95% CI 13.0\u201319.1]), fasting glucose (\u03b2 = 1.8% [95% CI 1.2\u20132.4]), 2-h glucose (\u03b2 = 5.2% [95% CI 3.7\u20136.7]), and area under the curve for glucose (\u03b2 = 3.6% [95% CI 2.7\u20134.6]). In addition, greater changes in C3 (per 0.1 g\/L) were associated with greater changes in HOMA2-IR (\u03b2 = 0.08 [95% CI 0.02\u20130.15]) and greater changes in hepatic IR (\u03b2 = 0.87 [95% CI 0.12\u20131.61]) over 7 years, but not glucose tolerance. Moreover, baseline C3 was associated with the 7-year incidence of T2DM (odds ratio 1.5 [95% CI 1.1\u20132.0]).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Changes in C3 were associated with changes in several measures of IR and may reflect progression of metabolic dysregulation, which eventually leads to abnormalities in glucose tolerance and T2DM.<\/jats:p><\/jats:sec>","DOI":"10.2337\/dc13-2804","type":"journal-article","created":{"date-parts":[[2014,4,24]],"date-time":"2014-04-24T08:26:50Z","timestamp":1398328010000},"page":"1900-1909","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":79,"title":["Complement Factor 3 Is Associated With Insulin Resistance and With Incident Type 2 Diabetes Over a 7-Year Follow-up Period: The CODAM Study"],"prefix":"10.2337","volume":"37","author":[{"given":"Nick","family":"Wlazlo","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Catharina Hospital, Eindhoven, the Netherlands"},{"name":"CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands"},{"name":"Department of Internal Medicine\/Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen M.J.","family":"van Greevenbroek","sequence":"additional","affiliation":[{"name":"CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands"},{"name":"Department of Internal Medicine\/Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Ferreira","sequence":"additional","affiliation":[{"name":"CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands"},{"name":"Department of Internal Medicine\/Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands"},{"name":"Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, the Netherlands"},{"name":"CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith J.M.","family":"Feskens","sequence":"additional","affiliation":[{"name":"Division of Human Nutrition, Section of Nutrition and Epidemiology, Wageningen University, Wageningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla J.H.","family":"van der Kallen","sequence":"additional","affiliation":[{"name":"CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands"},{"name":"Department of Internal Medicine\/Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper G.","family":"Schalkwijk","sequence":"additional","affiliation":[{"name":"CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands"},{"name":"Department of Internal Medicine\/Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Bravenboer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Catharina Hospital, Eindhoven, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coen D.A.","family":"Stehouwer","sequence":"additional","affiliation":[{"name":"CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands"},{"name":"Department of Internal Medicine\/Laboratory for Metabolism and 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