Hypoglycemia and glycemic variability in acute myocardial infarction: the lesser-known aspects of glycemic control.

Glucose abnormalities are common in patients with acute myocardial infarction (AMI) and significantly influence prognosis. While acute hyperglycemia on admission has long been recognized as a predictor of adverse outcomes, growing evidence suggests that hypoglycemia and glycemic variability (GV) are equally, if not more, prognostically relevant. These glycemic excursions, whether spontaneous or iatrogenic, are associated with increased risks of mortality, reinfarction, heart failure, and arrhythmias. The underlying mechanisms include sympathetic overactivation, endothelial dysfunction, inflammation, oxidative stress, thrombogenesis, and electrophysiological instability. Despite their clinical significance, hypoglycemia and GV remain insufficiently addressed in current AMI management protocols. Glycemic variability is often assessed through heterogeneous metrics-such as standard deviation, coefficient of variation, and mean amplitude of glycemic excursions, limiting comparability across studies. Additionally, reliance on intermittent glucose monitoring hinders accurate detection of hypoglycemic episodes, particularly those that are asymptomatic or nocturnal. The interaction between acute glycemic fluctuations and myocardial ischemia is also poorly understood, and the efficacy of interventions specifically targeting these disturbances remains to be established. Moreover, while observational studies have linked both hypoglycemia and GV with poor outcomes in AMI, interventional trials specifically targeting these abnormalities are lacking. This review aims to synthesize current evidence on the clinical and prognostic significance of hypoglycemia and GV in patients with AMI, offering an integrative overview of their prevalence, underlying mechanisms, and impact on outcomes, while highlighting key knowledge gaps and directions for future research.