Impact of insulin resistance and microvascular ischemia on myocardial energy metabolism and cardiovascular function: pathophysiology and therapeutic approaches

Insulin resistance (IR) and microvascular ischemia together result in cardiovascular dysfunction by impairing the heart’s energy balance. IR in cardiomyocytes disrupts glucose metabolism, leading to energy deficits that can drive cardiac hypertrophy and heart failure. Microvascular ischemia exacerbates these effects by limiting oxygen and nutrient delivery, intensifying oxidative stress, mitochondrial dysfunction, and cell death. IR also reduces the effectiveness of vasodilators like nitroglycerin and sodium nitroprusside, exacerbating endothelial dysfunction and oxidative stress, thus impairing oxygen delivery during ischemia. This combination of IR and microvascular ischemia heightens the risk of left ventricular dysfunction and heart failure. Understanding these interactions is critical for developing targeted therapies to improve outcomes in patients with IR and ischemic heart disease. This study examines the relationship between IR, microvascular ischemia, and myocardial metabolism, with a focus on clinical management and therapeutic strategies.