Potential Role of Metal Chelation to Prevent the Cardiovascular Complications of Diabetes

J Clin Endocrinol Metab. 2019 Jul 1;104(7):2931-2941. doi: 10.1210/jc.2018-01484.


Context: For decades, there has been epidemiologic evidence linking chronic toxic metal exposure with cardiovascular disease, suggesting a therapeutic role for metal chelation. Given the lack of compelling scientific evidence, however, the indications for metal chelation were never clearly defined. To determine the safety and efficacy of chelation therapy, the National Institutes of Health funded the Trial to Assess Chelation Therapy (TACT). TACT was the first double-blind, randomized, controlled trial to demonstrate an improvement in cardiovascular outcomes with edetate disodium therapy in patients with prior myocardial infarction. The therapeutic benefit was striking among the prespecified subgroup of patients with diabetes.

Design: We review the published literature focusing on the atherogenic nature of diabetes, as well as available evidence from clinical trials, complete and in progress, of metal chelation with edetate disodium therapy in patients with diabetes.

Results: The TACT results support the concept that ubiquitous toxic metals such as lead and cadmium may be modifiable risk factors for cardiovascular disease, particularly in patients with diabetes.

Conclusions: The purpose of this review is to discuss the potential mechanisms unifying the pathogenesis of atherogenic factors in diabetes with toxic metal exposure, and the potential role of metal chelation.

Publication types

  • Review

MeSH terms

  • Antioxidants / therapeutic use
  • Arsenic / metabolism
  • Ascorbic Acid / therapeutic use
  • Atherosclerosis / metabolism
  • Cadmium / metabolism
  • Calcium Chelating Agents / therapeutic use*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Chelating Agents / therapeutic use
  • Chelation Therapy
  • Copper / metabolism
  • Diabetes Complications / metabolism
  • Diabetes Complications / prevention & control*
  • Diabetes Mellitus / metabolism*
  • Edetic Acid / therapeutic use*
  • Glycation End Products, Advanced / metabolism
  • Hospitalization / statistics & numerical data
  • Humans
  • Iron / metabolism
  • Lead / metabolism
  • Lipid Metabolism
  • Mercury / metabolism
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / prevention & control
  • Myocardial Revascularization / statistics & numerical data
  • Oxidative Stress
  • Randomized Controlled Trials as Topic
  • Stroke / epidemiology
  • Stroke / prevention & control


  • Antioxidants
  • Calcium Chelating Agents
  • Chelating Agents
  • Glycation End Products, Advanced
  • Cadmium
  • Lead
  • Copper
  • Edetic Acid
  • Iron
  • Mercury
  • Arsenic
  • Ascorbic Acid