{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T06:57:25Z","timestamp":1781938645532,"version":"3.54.5"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100014584","name":"Universit\u00e4tsmedizin der Johannes Gutenberg-Universit\u00e4t Mainz","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014584","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Diabetol"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Cardiac autonomic dysfunction plays a pivotal role in the heart failure syndrome. Metabolic dysregulation affects both autonomic function and heart failure, but these relationships remain incompletely understood. This study aimed at investigating the role of glucose and insulin metabolism for parasympathetic reactivation.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Data from the MyoVasc study (NCT04064450), a prospective heart failure cohort study, were analyzed. Participants underwent a highly standardized 5-hour examination, including venous blood sampling. To assess the impact of glucose and insulin metabolism (HbA\n 1c<\/jats:sub>\n , HOMA-IR, and C-peptide) on parasympathetic reactivation as reflected by heart rate recovery 60\u00a0s (HRR\n 60<\/jats:sub>\n ) after cardiopulmonary exercise testing, multivariable linear regression models with adjustment for sex, age, clinical profile (cardiovascular risk factors and comorbidities) and medication were calculated in cross-sectional and longitudinal settings. Additional adjustment for complementary glucose or insulin status was performed to assess the dependency of each other. Analyses were carried out in symptomatic heart failure and across the spectrum of glucose metabolism dysfunction.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The analysis sample included 1,588 individuals (median age 64.0 years [IQR 55.0;72.0]; 33% women) in a fasting state. Symptomatic heart failure was present in 43.7% of the subjects. Median HRR\n 60<\/jats:sub>\n was 21.0 beats per minute (IQR 14.0;28.0). In multivariable regression analysis with adjustment for age, sex, clinical profile, and medication, both HbA\n 1c<\/jats:sub>\n (\n \n $$\\:\\widehat{{\\upbeta\\:}}$$<\/jats:tex-math>\n <\/jats:inline-formula>\n per SD<\/jats:sub>\n \u22120.074, 95% CI [\u2212\u20090.122;\u22120.026],\n P<\/jats:italic>\n \u2009=\u20090.003) and HOMA-IR (\n \n $$\\:\\widehat{{\\upbeta\\:}}$$<\/jats:tex-math>\n <\/jats:inline-formula>\n per SD<\/jats:sub>\n \u22120.113 [\u2212\u20090.165;\u22120.062],\n P<\/jats:italic>\n \u2009<\u20090.0001) predicted HRR\n 60<\/jats:sub>\n . Additional adjustment for both glucose and insulin status, respectively, demonstrated that HOMA-IR (\n \n $$\\:\\widehat{{\\upbeta\\:}}$$<\/jats:tex-math>\n <\/jats:inline-formula>\n per SD<\/jats:sub>\n \u22120.097 [\u2212\u20090.155;\u22120.040],\n P<\/jats:italic>\n \u2009<\u20090.0001), but not HbA\n 1c<\/jats:sub>\n (\n \n $$\\:\\widehat{{\\upbeta\\:}}$$<\/jats:tex-math>\n <\/jats:inline-formula>\n per SD<\/jats:sub>\n \u22120.030 [\u2212\u20090.084;0.025],\n P<\/jats:italic>\n \u2009=\u20090.28), was independently related to HRR\n 60<\/jats:sub>\n . This finding was confirmed in subgroups with heart failure and type 2 diabetes. In all analyses, C-peptide was related to HRR\n 60<\/jats:sub>\n independently of HbA\n 1c<\/jats:sub>\n with higher effect estimates than HOMA-IR (\n \n $$\\:\\widehat{{\\upbeta\\:}}$$<\/jats:tex-math>\n <\/jats:inline-formula>\n per SD<\/jats:sub>\n \u22120.171 [\u2212\u20090.225;\u22120.117],\n P<\/jats:italic>\n \u2009<\u20090.0001). Finally, higher HbA\n 1c<\/jats:sub>\n (\n \n $$\\:\\widehat{{\\upbeta\\:}}$$<\/jats:tex-math>\n <\/jats:inline-formula>\n per SD<\/jats:sub>\n \u22120.094, [\u2212\u20090.171;\u22120.017],\n P<\/jats:italic>\n \u2009=\u20090.017) and C-peptide (\n \n $$\\:\\widehat{{\\upbeta\\:}}$$<\/jats:tex-math>\n <\/jats:inline-formula>\n per SD<\/jats:sub>\n \u22120.076, [\u2212\u20090.159;0.007],\n P<\/jats:italic>\n \u2009=\u20090.075) were more strongly associated with a lower HRR\n 60<\/jats:sub>\n after two years of follow-up.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This study demonstrates the relevance of insulin status for vagal activity of cardiac autonomic function, particularly in heart failure. The pathophysiological implications underlying the relationship between insulin status and parasympathetic activity merit further mechanistic exploration.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12933-025-03040-9","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T15:34:00Z","timestamp":1767886440000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cardiac vagal activity is associated with insulin metabolism in heart failure: Results from the Myovasc study"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9267-8788","authenticated-orcid":false,"given":"No\u00e9mie","family":"B\u00e9langer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silav","family":"Zeid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3714-312X","authenticated-orcid":false,"given":"David","family":"Velmeden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1394-680X","authenticated-orcid":false,"given":"Andreas","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-8917","authenticated-orcid":false,"given":"Thomas","family":"Koeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7328-1056","authenticated-orcid":false,"given":"Felix","family":"Rausch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Foo\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8245-8243","authenticated-orcid":false,"given":"Fawad","family":"Kazemi-Asrar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1985-7931","authenticated-orcid":false,"given":"Karl J.","family":"Lackner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2917-6707","authenticated-orcid":false,"given":"Tommaso","family":"Gori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-4150","authenticated-orcid":false,"given":"Tommaso","family":"M\u00fcnzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5078-9992","authenticated-orcid":false,"given":"J\u00fcrgen H.","family":"Prochaska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7996-4034","authenticated-orcid":false,"given":"Perikles","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4413-9752","authenticated-orcid":false,"given":"Philipp S.","family":"Wild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"issue":"11","key":"3040_CR1","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1161\/CIRCRESAHA.114.302589","volume":"114","author":"VG Florea","year":"2014","unstructured":"Florea VG, Cohn JN. 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Outside the submitted work, P.S. Wild reports grants from Bayer AG, non-financial grants from Philips Medical Systems, grants and consulting fees from Boehringer Ingelheim, grants and consulting fees from Novartis Pharma, grants and consulting fees from Sanofi-Aventis, grants, consulting and lecturing fees from Bayer Health Care, grants and consulting fees from Daiichi Sankyo Europe, lecturing fees from Pfizer Pharma, lecturing fees from Bristol Myers Squibb, consulting fees from Astra Zeneca, consulting fees and non-financial support from Diasorin and non-financial support from IEM. PSW is funded by the European Regional Development Fund and the Ministry of Science and Health of the State of Rhineland-Palatinate (EFRE\/REACT-EU, Grant No. 84007232 and No. 84009735), the Federal Ministry of Education and Research (BMBF 01EO1503, 81Z0210103, 81Z0210102, 03ZU1202AA, 03ZU1202CD, 03ZU1202DB, 03ZU1202JC, 03ZU1202KB, 03ZU1202LB, 03ZU1202MB, 03ZU1202OA), Ministry of Science and Health of the State of Rhineland Palatinate (MWG RLP 724-0010#2021\/0030-1501), the ReALity Initiative of the Life Sciences of the Johannes Gutenberg University Mainz for the establishment of a cell bank, the National Research Network University Medicine on Covid-19 (\u201dNaFoUniMedCovid19\u201d, Grant No. 01KX2021) B-FAST, and the Federal Institute for Occupational Safety and Health (BAuA, F2447 \/ 537727) outside the present work. PSW is principal investigator of the German Center for Cardiovascular Research (DZHK), principal investigator of the DIASyM research core (BMBF DIASyM research core (BMBF 161L0217A, 031L0217A, 16LW0241K), of the future cluster curATime (BMBF 03ZU1202AA, 03ZU1202CD, 03ZU1202DB, 03ZU1202JC, 03ZU1202KB, 03ZU1202LB, 03ZU1202MB, and 03ZU1202OA) principal investigator of EPIC-AI (BMBF 01EQ2401A) and principal investigator of Multi-dimensionAI (CZS-Project number: P2022-08-010), funded by the Carl-Zeiss-Stiftung.J.H. Prochaska has received honoraria for lectures from Bayer AG, Boehringer Ingelheim, Daiichi Sankyo GmbH, and Sanofi-Aventis GmbH as well as research grants from the Federal Ministry of Education and Research (BMBF 01EO1503) and the German Center for Cardiovascular Research (DZHK) outside the topic of the present study. J.H. Prochaska is currently an employee of Boehringer Ingelheim and the University Medical Center Mainz.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26"}}