Glucose Disposal Rate: A Novel Measure of Insulin Resistance Associated With Myocardial Fibrosis and Incident Heart Failure

BACKGROUND: Heart failure (HF) is increasingly driven by cardiometabolic risk factors such as obesity and insulin resistance. The estimated glucose disposal rate (eGDR) is a validated surrogate marker of insulin resistance. Reduced eGDR, reflecting higher insulin resistance, has been linked to cardiovascular disease, but its associations with myocardial fibrosis and HF remain unclear. METHODS: The study included 6025 participants in MESA (Multi-Ethnic Study of Atherosclerosis) free of HF at exam 2 (2002-2004). eGDR was calculated using body mass index, hypertension, and hemoglobin A1c. Cardiac magnetic resonance imaging (2010-2012) assessed left ventricular ejection fraction and myocardial fibrosis by late gadolinium enhancement. Associations of baseline eGDR with incident HF were evaluated using Cox models, stratified by diabetes. RESULTS: Over a mean follow-up of 14±5 years, 404 participants developed HF. eGDR was inversely associated with incident HF (adjusted hazard ratio [HR] per unit decrease, 1.28 [95% CI, 1.22-1.35]), a relationship that persisted regardless of diabetes status and was more pronounced for HF with preserved ejection fraction (n=200; adjusted HR per unit decrease, 1.36 [95% CI, 1.27-1.45]) than HF with reduced ejection fraction (n=168; HR, 1.19 [95% CI, 1.11-1.27]). Lower eGDR was also associated with higher left ventricular ejection fraction (n=2899; β=0.16, [95% CI, 0.03-0.28]) and higher odds of myocardial fibrosis (n=1780; adjusted odds ratio, 1.27 [95% CI, 1.16-1.41]). CONCLUSIONS: Lower eGDR is independently associated with subclinical myocardial damage and incident HF, highlighting insulin resistance as a key driver of adverse remodeling and a potential marker for early HF risk stratification and prevention.