Journal of the American College of Cardiology

Can Type 2 Diabetes Change the Risk of Developing and Worsening Heart Failure with Normal Pumping Function?

Updated

Abstract

Type 2 diabetes is associated with an increased risk of heart failure with preserved ejection fraction (HFpEF), primarily due to excess adiposity.

  • Hyperglycemia may not be a direct cause of HFpEF, as treatments aimed at lowering blood glucose have not reduced heart failure risk.
  • The link between type 2 diabetes and HFpEF is mainly mediated by central obesity and increased visceral fat mass.
  • Excess adiposity can lead to systemic insulin resistance and contribute to cardiac dysfunction through the release of inflammatory substances.
  • The diabetic heart is primarily impacted by lipid overload rather than impaired glucose uptake.
  • Medications like glucagon-like peptide receptor agonists may improve heart function by mimicking caloric deprivation rather than directly lowering blood sugar.

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Funding

Competing interests

Funding Support and Author Disclosures Dr Packer has received consulting fees from Abbvie, Actavis, Alnylam, Altimmune, Ardelyx, Amgen, ARMGO, AstraZeneca, Attralus, Biopeutics, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Daiichi Sankyo, Eli Lilly and Company, Imara, Medtronic, Moderna, Novartis, Pharmacosmos, Regeneron, and Salamandra. Dr Lam has received support from Novo Nordisk and Roche Diagnostics; has served as consultant or on the advisory board/steering committee/executive committee for Alnylam Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Corteria, CPC Clinical Research, Cytokinetics, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research and Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Quidel Corporation, Radcliffe Group Ltd, Roche, and Us2.ai 3; and is the cofounder and non-executive director of Us2.ai. Dr Butler has served as a consultant for Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Bearing, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Levator, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron, Renibus, Roche, Salamandra, Salubris, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. Dr Zannad has served as a consultant for Alnylam, Bayer, Biopeutics, Boehringer, Cellprothera, Cereno, Centrix, Corteria, CVRx, CVCT, Lilly, Lupin, Merck, Novo Nordisk, Opalia Recordati, Owkin, Polygon, Ribocure, Riche, and Viatri; is on steering committees and DSMB and advisory boards for Alnylam, Bayer, Biopeutics, Boehringer, Cellprothera, Cereno, Corteria, CVRx, Merck, Owkin, Ribocure, and Roche; owns equities and stock options for Polygon, Cereno pharmaceutical, and CVCT; and is on the Speakers Bureau for Bayer, Boehringer, Centrix, CVRx, Lupin, Opalia Recordati, Merck, Novo Nordisk, and Viatris. Dr Vaduganathan has received research grant support, served on advisory boards, or had speaker engagements with Alnylam Pharmaceuticals, American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Cytokinetics, Esperion, Fresenius Medical Care, Idorsia Pharmaceuticals, Lexicon Pharmaceuticals, Merck, Milestone Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Recordati, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and participates on clinical trial committees for studies sponsored by Amgen, AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, Pharmacosmos, and Impulse Dynamics. Dr Borlaug receives research support from the National Institutes of Health and the U.S. Department of Defense; receives research grant funding from AstraZeneca, Axon, Corvia, Novo Nordisk, and Tenax Therapeutics; has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations; and is named inventor (US Patent number 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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