{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:39:36Z","timestamp":1790991576566,"version":"4.1.0"},"reference-count":32,"publisher":"American Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":48,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"name":"Iacocca Foundation","award":["Mary K. Iacocca Fellowship"],"award-info":[{"award-number":["Mary K. Iacocca Fellowship"]}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK107956-01"],"award-info":[{"award-number":["R01 DK107956-01"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01 DK119083"],"award-info":[{"award-number":["U01 DK119083"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008871","name":"JDRF","doi-asserted-by":"publisher","award":["DK36836"],"award-info":[{"award-number":["DK36836"]}],"id":[{"id":"10.13039\/100008871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95178"],"award-info":[{"award-number":["N01-HC-95178"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95179"],"award-info":[{"award-number":["N01-HC-95179"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95180"],"award-info":[{"award-number":["N01-HC-95180"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95181"],"award-info":[{"award-number":["N01-HC-95181"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95182"],"award-info":[{"award-number":["N01-HC-95182"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95183"],"award-info":[{"award-number":["N01-HC-95183"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["N01-HC-95184"],"award-info":[{"award-number":["N01-HC-95184"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["IAA-Y1-HC-9035"],"award-info":[{"award-number":["IAA-Y1-HC-9035"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["IAA-Y1-HC-1010"],"award-info":[{"award-number":["IAA-Y1-HC-1010"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>The effects of preventive interventions on cardiovascular autonomic neuropathy (CAN) remain unclear. We examined the effect of intensively treating traditional risk factors for CAN, including hyperglycemia, hypertension, and dyslipidemia, in individuals with type 2 diabetes (T2D) and high cardiovascular risk participating in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>CAN was defined as heart rate variability indices below the fifth percentile of the normal distribution. Of 10,251 ACCORD participants, 71% (n = 7,275) had a CAN evaluation at study entry and at least once after randomization. The effects of intensive interventions on CAN were analyzed among these subjects through generalized linear mixed models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>As compared with standard intervention, intensive glucose treatment reduced CAN risk by 16% (odds ratio [OR] 0.84, 95% CI 0.75\u20130.94, P = 0.003)\u2014an effect driven by individuals without cardiovascular disease (CVD) at baseline (OR 0.73, 95% CI 0.63\u20130.85, P &amp;lt; 0.0001) rather than those with CVD (OR 1.10, 95% CI 0.91\u20131.34, P = 0.34) (Pinteraction = 0.001). Intensive blood pressure (BP) intervention decreased CAN risk by 25% (OR 0.75, 95% CI 0.63\u20130.89, P = 0.001), especially in patients \u226565 years old (OR 0.66, 95% CI 0.49\u20130.88, P = 0.005) (Pinteraction = 0.05). Fenofibrate did not have a significant effect on CAN (OR 0.91, 95% CI 0.78\u20131.07, P = 0.26).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>These data confirm a beneficial effect of intensive glycemic therapy and demonstrate, for the first time, a similar benefit of intensive BP control on CAN in T2D. A negative CVD history identifies T2D patients who especially benefit from intensive glycemic control for CAN prevention.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc20-1842","type":"journal-article","created":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T04:00:14Z","timestamp":1604462414000},"page":"164-173","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":60,"title":["Intensive Risk Factor Management and Cardiovascular Autonomic Neuropathy in Type 2 Diabetes: The ACCORD Trial"],"prefix":"10.2337","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct00000620","registry":"10.18810\/clinical-trials-gov","type":"results"}],"author":[{"given":"Yaling","family":"Tang","sequence":"first","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Boston, MA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-4572","authenticated-orcid":false,"given":"Hetal","family":"Shah","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Boston, MA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Roberto","family":"Bueno Junior","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuqin","family":"Sun","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Boston, MA"},{"name":"Department of Endocrinology and Metabolism, Anzhen Hospital Affiliated to Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Mitri","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Boston, MA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9259-8366","authenticated-orcid":false,"given":"Maria","family":"Sambataro","sequence":"additional","affiliation":[{"name":"Endocrine, Metabolism and Nutrition Disease Unit, Internal Medicine Department, Santa Maria of Ca\u2019 Foncello Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Sambado","sequence":"additional","affiliation":[{"name":"Endocrine, Metabolism and Nutrition Disease Unit, Internal Medicine Department, Santa Maria of Ca\u2019 Foncello Hospital, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8072-2836","authenticated-orcid":false,"given":"Hertzel C.","family":"Gerstein","sequence":"additional","affiliation":[{"name":"McMaster University and the Population Health Research Institute, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3381-7151","authenticated-orcid":false,"given":"Vivian","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Tulane University Health Sciences Center, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3830-4304","authenticated-orcid":false,"given":"Alessandro","family":"Doria","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center, Boston, MA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2042-1350","authenticated-orcid":false,"given":"Rodica","family":"Pop-Busui","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2020,11,3]]},"reference":[{"key":"2022031222424848100_B1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.2337\/dc16-2042","article-title":"Diabetic neuropathy: a position statement by the American Diabetes Association","volume":"40","author":"Pop-Busui","year":"2017","journal-title":"Diabetes Care"},{"key":"2022031222424848100_B2","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.2337\/dc10-1303","article-title":"Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments","volume":"33","author":"Tesfaye","year":"2010","journal-title":"Diabetes Care"},{"key":"2022031222424848100_B3","doi-asserted-by":"crossref","first-page":"914","DOI":"10.2337\/diacare.29.04.06.dc05-1729","article-title":"The association among autonomic nervous system function, incident diabetes, and intervention arm in the Diabetes Prevention Program","volume":"29","author":"Carnethon","year":"2006","journal-title":"Diabetes Care"},{"key":"2022031222424848100_B4","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1007\/s00125-015-3534-7","article-title":"Increased prevalence of cardiac autonomic dysfunction at different degrees of glucose intolerance in the general population: the KORA S4 survey","volume":"58","author":"Ziegler","year":"2015","journal-title":"Diabetologia"},{"key":"2022031222424848100_B5","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1111\/j.1464-5491.2011.03278.x","article-title":"Cardiovascular autonomic dysfunction is associated with central obesity in persons with impaired glucose tolerance","volume":"28","author":"Laitinen","year":"2011","journal-title":"Diabet Med"},{"key":"2022031222424848100_B6","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1001\/jama.2017.0686","article-title":"Association of type 1 diabetes vs type 2 diabetes diagnosed during childhood and adolescence with complications during teenage years and young adulthood","volume":"317","author":"Dabelea","year":"2017","journal-title":"JAMA"},{"key":"2022031222424848100_B7","doi-asserted-by":"crossref","first-page":"94","DOI":"10.2337\/dc16-1397","article-title":"Cardiovascular autonomic neuropathy and cardiovascular outcomes in the Diabetes Control and Complications Trial\/Epidemiology of Diabetes Interventions and Complications (DCCT\/EDIC) study","volume":"40","author":"Pop-Busui","year":"2017","journal-title":"Diabetes Care"},{"key":"2022031222424848100_B8","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/oxfordjournals.eurheartj.a014868","article-title":"Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology","volume":"17","year":"1996","journal-title":"Eur Heart J"},{"key":"2022031222424848100_B9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4093\/dmj.2018.0259","article-title":"Update on the impact, diagnosis and management of cardiovascular autonomic neuropathy in diabetes: what is defined, what is new, and what is unmet","volume":"43","author":"Spallone","year":"2019","journal-title":"Diabetes Metab J"},{"key":"2022031222424848100_B10","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1056\/NEJMoa021778","article-title":"Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes","volume":"348","author":"Gaede","year":"2003","journal-title":"N Engl J Med"},{"key":"2022031222424848100_B11","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/S2213-8587(19)30349-3","article-title":"Long-term effects of intensive multifactorial therapy in individuals with screen-detected type 2 diabetes in primary care: 10-year follow-up of the ADDITION-Europe cluster-randomised trial","volume":"7","author":"Griffin","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2022031222424848100_B12","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1001\/jama.2016.13985","article-title":"Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis","volume":"316","author":"Silverman","year":"2016","journal-title":"JAMA"},{"key":"2022031222424848100_B13","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0140-6736(15)00805-3","article-title":"Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis","volume":"387","author":"Xie","year":"2016","journal-title":"Lancet"},{"key":"2022031222424848100_B14","doi-asserted-by":"crossref","first-page":"21i","DOI":"10.1016\/j.amjcard.2007.03.003","article-title":"Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods","volume":"99","author":"Accord Study Group","year":"2007","journal-title":"Am J Cardiol"},{"key":"2022031222424848100_B15","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1056\/NEJMoa0802743","article-title":"Effects of intensive glucose lowering in type 2 diabetes","volume":"358","author":"Action to Control Cardiovascular Risk in Diabetes Study Group","year":"2008","journal-title":"N Engl J Med"},{"key":"2022031222424848100_B16","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.2337\/dc10-0125","article-title":"Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial","volume":"33","author":"Pop-Busui","year":"2010","journal-title":"Diabetes Care"},{"key":"2022031222424848100_B17","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.jelectrocard.2016.06.008","article-title":"Reference ranges for short-term heart rate variability measures in individuals free of cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"49","author":"O\u2019Neal","year":"2016","journal-title":"J Electrocardiol"},{"key":"2022031222424848100_B18","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1056\/NEJMoa0806470","article-title":"10-Year follow-up of intensive glucose control in type 2 diabetes","volume":"359","author":"Holman","year":"2008","journal-title":"N Engl J Med"},{"key":"2022031222424848100_B19","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s11892-010-0120-8","article-title":"DCCT and EDIC studies in type 1 diabetes: lessons for diabetic neuropathy regarding metabolic memory and natural history","volume":"10","author":"Pop-Busui","year":"2010","journal-title":"Curr Diab Rep"},{"key":"2022031222424848100_B20","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.2337\/db19-1046","article-title":"Risk factors for diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in the Diabetes Control and Complications Trial\/Epidemiology of Diabetes Interventions and Complications (DCCT\/EDIC) study","volume":"69","author":"Braffett","year":"2020","journal-title":"Diabetes"},{"key":"2022031222424848100_B21","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1056\/NEJMoa0808431","article-title":"Glucose control and vascular complications in veterans with type 2 diabetes","volume":"360","author":"Duckworth","year":"2009","journal-title":"N Engl J Med"},{"key":"2022031222424848100_B22","first-page":"1106","article-title":"Hypertension, blood pressure, and heart rate variability: the Atherosclerosis Risk in Communities (ARIC) study","volume-title":"Hypertension","author":"Schroeder","year":"2003"},{"key":"2022031222424848100_B23","first-page":"888","article-title":"Orthostatic hypotension in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial: prevalence, incidence, and prognostic significance","volume-title":"Hypertension","author":"Fleg","year":"2016"},{"key":"2022031222424848100_B24","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s11906-016-0625-x","article-title":"Major autonomic neuroregulatory pathways underlying short- and long-term control of cardiovascular function","volume":"18","author":"Salman","year":"2016","journal-title":"Curr Hypertens Rep"},{"key":"2022031222424848100_B25","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1111\/pedi.12633","article-title":"Cardiovascular autonomic neuropathy in adolescents and young adults with type 1 and type 2 diabetes: the SEARCH for Diabetes in Youth Cohort Study","volume":"19","author":"Jaiswal","year":"2018","journal-title":"Pediatr Diabetes"},{"key":"2022031222424848100_B26","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.2337\/dc18-1411","article-title":"Risk factors for the presence and progression of cardiovascular autonomic neuropathy in type 2 diabetes: ADDITION-Denmark","volume":"41","author":"Andersen","year":"2018","journal-title":"Diabetes Care"},{"key":"2022031222424848100_B27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s12264-018-0271-1","article-title":"Anti-hypertensive action of fenofibrate via UCP2 upregulation mediated by PPAR activation in baroreflex afferent pathway","volume":"35","author":"Guan","year":"2019","journal-title":"Neurosci Bull"},{"key":"2022031222424848100_B28","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ejphar.2011.03.056","article-title":"Fenofibrate increases neuronal vasoconstrictor response in mesenteric arteries from diabetic rats: role of noradrenaline, neuronal nitric oxide and calcitonin gene-related peptide","volume":"666","author":"del Campo","year":"2011","journal-title":"Eur J Pharmacol"},{"key":"2022031222424848100_B29","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.jacl.2015.03.011","article-title":"Fenofibrate lowers atypical sphingolipids in plasma of dyslipidemic patients: a novel approach for treating diabetic neuropathy","volume":"9","author":"Othman","year":"2015","journal-title":"J Clin Lipidol"},{"key":"2022031222424848100_B30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.atherosclerosis.2016.11.032","article-title":"Markers of sympathetic nervous system activity associate with complex plasma lipids in metabolic syndrome subjects","volume":"256","author":"Nestel","year":"2017","journal-title":"Atherosclerosis"},{"key":"2022031222424848100_B31","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0002-9149(03)00643-X","article-title":"Effect of atorvastatin and fenofibrate on autonomic tone in subjects with combined hyperlipidemia","volume":"92","author":"Melenovsky","year":"2003","journal-title":"Am J Cardiol"},{"key":"2022031222424848100_B32","doi-asserted-by":"crossref","first-page":"556","DOI":"10.2337\/dc07-1615","article-title":"Prediction of mortality using measures of cardiac autonomic dysfunction in the diabetic and nondiabetic population: the MONICA\/KORA Augsburg Cohort Study","volume":"31","author":"Ziegler","year":"2008","journal-title":"Diabetes Care"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/care.diabetesjournals.org\/syndication\/doi\/10.2337\/dc20-1842","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/44\/1\/164\/532217\/dc201842.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/44\/1\/164\/532217\/dc201842.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T00:59:07Z","timestamp":1647133147000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/44\/1\/164\/33243\/Intensive-Risk-Factor-Management-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,3]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,11,3]]},"published-print":{"date-parts":[[2021,1,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc20-1842","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,3]]}}}