{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:37:27Z","timestamp":1789983447154,"version":"4.0.1"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2019,2,5]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Poor glycemic control is associated with increased risk of cardiovascular disease (CVD) in type 1 diabetes mellitus (T1DM); however, little is known about mechanisms specific to T1DM. In T1DM, myocardial injury can induce persistent cardiac autoimmunity. Chronic hyperglycemia causes myocardial injury, raising the possibility that hyperglycemia-induced cardiac autoimmunity could contribute to long-term CVD complications in T1DM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              We measured the prevalence and profiles of cardiac autoantibodies (AAbs) in longitudinal samples from the DCCT (Diabetes Control and Complications Trial) in participants with mean hemoglobin A\n              <jats:sub>1c<\/jats:sub>\n              (HbA\n              <jats:sub>1c<\/jats:sub>\n              ) \u22659.0% (n=83) and \u22647.0% (n=83) during DCCT. We assessed subsequent coronary artery calcification (measured once during years 7\u20139 in the post-DCCT EDIC [Epidemiology of Diabetes Interventions and Complications] observational study), high-sensitivity C-reactive protein (measured during EDIC years 4\u20136), and CVD events (defined as nonfatal myocardial infarction, stroke, death resulting from CVD, heart failure, or coronary artery bypass graft) over a 26-year median follow-up. Cardiac AAbs were also measured in matched patients with type 2 diabetes mellitus with HbA\n              <jats:sub>1c<\/jats:sub>\n              \u22659.0% (n=70) and \u22647.0% (n=140) and, as a control for cardiac autoimmunity, patients with Chagas cardiomyopathy (n=51).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Apart from HbA\n              <jats:sub>1c<\/jats:sub>\n              levels, the DCCT groups shared similar CVD risk factors at the beginning and end of DCCT. The DCCT HbA\n              <jats:sub>1c<\/jats:sub>\n              \u22659.0% group showed markedly higher cardiac AAb levels than the HbA\n              <jats:sub>1c<\/jats:sub>\n              \u22647.0% group during DCCT, with a progressive increase and decrease in AAb levels over time in the 2 groups, respectively (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). In the HbA\n              <jats:sub>1c<\/jats:sub>\n              \u22659.0% group, 46%, 22%, and 11% tested positive for \u22651, \u22652, and \u22653 different cardiac AAb types, respectively, similar to patients with Chagas cardiomyopathy, compared with 2%, 1%, and 0% in the HbA\n              <jats:sub>1c<\/jats:sub>\n              \u22647.0% group. Glycemic control was not associated with AAb prevalence in type 2 diabetes mellitus. Positivity for \u22652 AAbs during DCCT was associated with increased risk of CVD events (4 of 6; hazard ratio, 16.1; 95% CI, 3.0\u201388.2) and, in multivariable analyses, with detectable coronary artery calcification (13 of 31; odds ratio, 60.1; 95% CI, 8.4\u2013410.0). Patients with \u22652 AAbs subsequently also showed elevated high-sensitivity C-reactive protein levels (6.0 mg\/L versus 1.4 mg\/L in patients with \u22641 AAbs;\n              <jats:italic>P<\/jats:italic>\n              =0.003).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Poor glycemic control is associated with cardiac autoimmunity in T1DM. Furthermore, cardiac AAb positivity is associated with an increased risk of CVD decades later, suggesting a role for autoimmune mechanisms in the development of CVD in T1DM, possibly through inflammatory pathways.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.118.036068","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T13:44:06Z","timestamp":1547732646000},"page":"730-743","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":101,"title":["Glycemic Control, Cardiac Autoimmunity, and Long-Term Risk of Cardiovascular Disease in Type 1 Diabetes Mellitus"],"prefix":"10.1161","volume":"139","author":[{"given":"Giovane R.","family":"Sousa","sequence":"first","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA (G.R.S., D.P., A.G., H.L., A.D., M.A.L.)."},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (G.R.S., H.L., A.D., M.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pober","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA (G.R.S., D.P., A.G., H.L., A.D., M.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Galderisi","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA (G.R.S., D.P., A.G., H.L., A.D., M.A.L.)."},{"name":"Department of Pediatrics, Yale University, New Haven, CT (A.G.)."},{"name":"Department of Women and Children\u2019s Health, University of Padova, Italy (A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HuiJuan","family":"Lv","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA (G.R.S., D.P., A.G., H.L., A.D., M.A.L.)."},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (G.R.S., H.L., A.D., M.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Yu","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Childhood Diabetes, University of Colorado, Anschutz Medical Campus, Aurora (L.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of Sao Paulo, Brazil (A.C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Doria","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA (G.R.S., D.P., A.G., H.L., A.D., M.A.L.)."},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (G.R.S., H.L., A.D., M.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Kosiborod","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Mid America Heart Institute, University of Missouri\u2013Kansas City (M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myra A.","family":"Lipes","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA (G.R.S., D.P., A.G., H.L., A.D., M.A.L.)."},{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (G.R.S., H.L., A.D., M.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1608664"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60471-6"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408214"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000034"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-er11"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.529651"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199309303291401"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052187"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0078"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.245"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.08.036"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043430"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.06.009"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030966"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60591-7"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.04.008"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a012831"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.7.926"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.03.018"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44583"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/414813a"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12537"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0617"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.10.875"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1990"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","unstructured":"Sousa GR Pober D Galderisi A Lv H Yu L Pereira AC Doria A Kosiborod M Lipes MA. Glycemic control cardiac autoimmunity and long-term risk of cardiovascular disease in type 1 diabetes: a DCCT\/EDIC cohort-based study. NIDDK Central Repository. 2019. https:\/\/repository.niddk.nih.gov\/studies\/edic\/.","DOI":"10.1161\/CIRCULATIONAHA.118.036068"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2008.649"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003551"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.624296"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.22.1.99"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1093"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003815"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0293"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0653"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780090710"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2007.01.009"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2007.02.003"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-0659"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.2337\/dci17-0053"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.05.054"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3667"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2012.07.005"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.6.859"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.010815"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI14452"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01323"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118969"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-1874"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.8.3541"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1108"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.118.036068","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T08:13:55Z","timestamp":1715588035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.118.036068"}},"subtitle":["A DCCT\/EDIC Cohort\u2013Based Study"],"short-title":[],"issued":{"date-parts":[[2019,2,5]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,2,5]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.118.036068"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.118.036068","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,5]]},"assertion":[{"value":"2018-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}