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Med."],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate the association between cardiovascular autonomic neuropathy and bone metabolism in people with Type 1 diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed cardiovascular autonomic neuropathy in 329 people with Type 1 diabetes according to heart rate response to deep breathing, to standing and to the Valsalva manoeuvre, and 2\u2010min resting heart rate. More than one pathological non\u2010resting test was defined as cardiovascular autonomic neuropathy. Bone mineral density of the femoral neck (<jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content>fn) was assessed by dual energy X\u2010ray absorptiometry. Serum parathyroid hormone levels and other bone markers were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean (<jats:sc>sd<\/jats:sc>) age of the participants was 55.6 (9.4) years, 52% were men, and the mean (<jats:sc>sd<\/jats:sc>) diabetes duration was 40 (8.9) years, HbA<jats:sub>1c<\/jats:sub> 62 (9) mmol\/mol and estimated <jats:styled-content style=\"fixed-case\">GFR<\/jats:styled-content> 78 (26) ml\/min\/1.73m<jats:sup>2<\/jats:sup>. In all, 36% had cardiovascular autonomic neuropathy. Participants with cardiovascular autonomic neuropathy had 4.2% (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> \u20138.0 to \u20130.2; <jats:italic>P<\/jats:italic>=0.038) lower <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content>fn and 33.6% (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 14.3 to 53.8; <jats:italic>P<\/jats:italic>=0.0002) higher parathyroid hormone levels compared with participants without cardiovascular autonomic neuropathy in adjusted models. Higher resting heart rate remained associated with higher parathyroid hormone level and lower <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content>fn after additional adjustment for <jats:styled-content style=\"fixed-case\">eGFR<\/jats:styled-content> (<jats:italic>P<\/jats:italic>&lt;0.0001 and <jats:italic>P =<\/jats:italic> 0.042, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The presence of cardiovascular autonomic neuropathy was associated with reduced <jats:styled-content style=\"fixed-case\">BMD<\/jats:styled-content>fn and increased levels of parathyroid hormone. Kidney function may either confound or mediate these findings. Cardiovascular autonomic neuropathy could be associated with increased risk of osteoporosis in Type 1 diabetes. Whether cardiovascular autonomic neuropathy directly affects bone metabolism detrimentally or if this association is mediated via decreased kidney function should be investigated further.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.13777","type":"journal-article","created":{"date-parts":[[2018,7,12]],"date-time":"2018-07-12T13:07:30Z","timestamp":1531400850000},"page":"1596-1604","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Cardiovascular autonomic neuropathy and bone metabolism in Type 1 diabetes"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5782-3476","authenticated-orcid":false,"given":"C. S.","family":"Hansen","sequence":"first","affiliation":[{"name":"Steno Diabetes Centre Copenhagen Gentofte Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Theilade","sequence":"additional","affiliation":[{"name":"Steno Diabetes Centre Copenhagen Gentofte Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Lajer","sequence":"additional","affiliation":[{"name":"Steno Diabetes Centre Copenhagen Gentofte Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. W.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Centre Copenhagen Gentofte Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Rossing","sequence":"additional","affiliation":[{"name":"Steno Diabetes Centre Copenhagen Gentofte Denmark"},{"name":"Department of Clinical Medicine Faculty of Health Aarhus Denmark"},{"name":"Department of Public Health Aarhus University Aarhus Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwm106"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4269-4"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-6632(90)90012-T"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001980050082"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-006-0253-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-6009(08)80105-5"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(99)00211-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.0301214"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000203845.26690.cb"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.11.1326"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2015.12.012"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(03)00095-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.1992.tb01898.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.12.2942"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-1615"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8227(02)00128-6"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2009.02.012"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0986"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2010.07.005"},{"key":"e_1_2_9_21_1","first-page":"151","article-title":"C. 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