Strategies of Unloading the Failing Heart from Metabolic Stress

Efstratios Koutroumpakis, Bartosz Jozwik, David Aguilar, Heinrich Taegtmeyer

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

We propose a unifying perspective of heart failure in patients with type 2 diabetes mellitus. The reasoning is as follows: cellular responses to fuel overload include dysregulated insulin signaling, impaired mitochondrial respiration, reactive oxygen species formation, and the accumulation of certain metabolites, collectively termed glucolipotoxicity. As a consequence, cardiac function is impaired, with intracellular calcium cycling and diastolic dysfunction as an early manifestation. In this setting, increasing glucose uptake by insulin or insulin sensitizing agents only worsens the disrupted fuel homeostasis of the heart. Conversely, restricting fuel supply by means of caloric restriction, surgical intervention, or certain pharmacologic agents will improve cardiac function by restoring metabolic homeostasis. The concept is borne out by clinical interventions, all of which unload the heart from metabolic stress.

Original languageEnglish
Pages (from-to)290-296
Number of pages7
JournalAmerican Journal of Medicine
Volume133
Issue number3
DOIs
StatePublished - Mar 2020

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • Fuel homeostasis
  • Fuel toxicity
  • Heart failure
  • Metabolic unloading

ASJC Scopus subject areas

  • General Medicine

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