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Cardiovascular toxicity refers to a broad spectrum of harmful effects from various agents on the heart and blood vessels, including structural damage, functional disturbances, and electrophysiological abnormalities. In diabetes mellitus (DM), these effects are further exacerbated by the complex interaction of chronic hyperglycemia and associated metabolic disorders. Key mechanisms underlying cardiovascular toxicity in DM include disruption of cardiac energy metabolism, chronic inflammation, oxidative stress, accumulation of advanced glycation end products (AGEs), mitochondrial dysfunction, endoplasmic reticulum stress, apoptosis of cardiomyocytes, and endothelial dysfunction. Novel biomarkers, such as high-sensitivity troponin (hs-cTn), homocysteine, natriuretic peptides (B-type natriuretic peptide—BNP and inactive component of its precursor—NT-proBNP), and heart-type fatty acid-binding protein (h-FABP), enable early detection and intervention in cardiovascular toxicity. Cardiovascular diseases remain the leading cause of morbidity and mortality in DM, despite intensive glycemic control. Novel antihyperglycemic agents, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 (DPP-4) inhibitors, along with well-known drugs like metformin, demonstrate promising cardioprotective effects that extend beyond their primary antihyperglycemic action. However, cardiovascular impact varies among different drug classes, even within the same class. Statins, in addition to their basic hypolipidemic effect, exhibit numerous pleiotropic effects that significantly contribute to reducing cardiovascular risk in both DM patients and the general population. When combined with statins, agents like ezetimibe, fibrates, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors further enhance cardiovascular risk reduction. Additionally, research has indicated potential cardioprotective effects of certain vitamins and trace elements in the context of DM. Understanding the mechanisms of cardiovascular toxicity in DM and the cardioprotective effects of various therapeutic modalities opens new perspectives in the prevention and treatment of cardiovascular complications associated with this condition.

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Cardiovascular Toxicity in Diabetes Mellitus: Focus on Diabetogenic and Anti-diabetogenic Agents

  • 章节

  • 发表日期：

    2025年

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  • Nina M. Radisavljevic,
  • Slavica S. Mutavdzin Krneta,
  • Dragan M. Djuric

摘要

Cardiovascular toxicity refers to a broad spectrum of harmful effects from various agents on the heart and blood vessels, including structural damage, functional disturbances, and electrophysiological abnormalities. In diabetes mellitus (DM), these effects are further exacerbated by the complex interaction of chronic hyperglycemia and associated metabolic disorders. Key mechanisms underlying cardiovascular toxicity in DM include disruption of cardiac energy metabolism, chronic inflammation, oxidative stress, accumulation of advanced glycation end products (AGEs), mitochondrial dysfunction, endoplasmic reticulum stress, apoptosis of cardiomyocytes, and endothelial dysfunction. Novel biomarkers, such as high-sensitivity troponin (hs-cTn), homocysteine, natriuretic peptides (B-type natriuretic peptide—BNP and inactive component of its precursor—NT-proBNP), and heart-type fatty acid-binding protein (h-FABP), enable early detection and intervention in cardiovascular toxicity. Cardiovascular diseases remain the leading cause of morbidity and mortality in DM, despite intensive glycemic control. Novel antihyperglycemic agents, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 (DPP-4) inhibitors, along with well-known drugs like metformin, demonstrate promising cardioprotective effects that extend beyond their primary antihyperglycemic action. However, cardiovascular impact varies among different drug classes, even within the same class. Statins, in addition to their basic hypolipidemic effect, exhibit numerous pleiotropic effects that significantly contribute to reducing cardiovascular risk in both DM patients and the general population. When combined with statins, agents like ezetimibe, fibrates, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors further enhance cardiovascular risk reduction. Additionally, research has indicated potential cardioprotective effects of certain vitamins and trace elements in the context of DM. Understanding the mechanisms of cardiovascular toxicity in DM and the cardioprotective effects of various therapeutic modalities opens new perspectives in the prevention and treatment of cardiovascular complications associated with this condition.