Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options.
Increasing evidence points to insulin resistance as a primary etiologic factor in the development of nonischemic heart failure (HF). The myocardium normally responds to injury by altering substrate metabolism to increase energy efficiency. Insulin resistance prevents this adaptive response and can lead to further injury by contributing to lipotoxicity, sympathetic up-regulation, inflammation, oxidative stress, and fibrosis. Animal models have repeatedly demonstrated the existence of an insulin-resistant cardiomyopathy, one that is characterized by inefficient energy metabolism and is reversible by improving energy use. Clinical studies in humans strongly support the link between insulin resistance and nonischemic HF. Insulin resistance is highly prevalent in the nonischemic HF population, predates the development of HF, independently defines a worse prognosis, and predicts response to antiadrenergic therapy. Potential options for treatment include metabolic-modulating agents and antidiabetic drugs. This article reviews the basic science evidence, animal experiments, and human clinical data supporting the existence of an "insulin-resistant cardiomyopathy" and proposes specific potential therapeutic approaches.
Witteles
Ronald M
RM
Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. witteles@stanford.edu
Fowler
Michael B
MB
D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones