Background and aims <p> The hemoglobin glycation index (HGI) has been linked to cardiovascular disease in diabetic patients. However, it remains unclear whether an elevated HGI similarly affects the cardiovascular system in individuals with normal glucose tolerance or prediabetes. In this cross-sectional study, we aimed to determine whether increased HGI levels are associated with a reduction in myocardial mechano-energetic efficiency (MEE), a key predictor of cardiovascular events and heart failure, in non-diabetic subjects.</p> Methods <p>Myocardial MEE per gram of left ventricular mass (MEEi) was assessed via echocardiography in a cohort of 1,074 adults with different glucose tolerance statuses, enrolled in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study. HGI was defined as the difference between the measured HbA1c and the predicted HbA1c, the latter calculated from the linear association between HbA1c and fasting plasma glucose levels.</p> Results <p>Subjects in the highest HGI quartile exhibited significantly elevated myocardial oxygen consumption and a marked reduction in MEEi compared to those in the lowest quartile. A significant inverse correlation was observed between HGI and MEEi (<i>r</i> = − 0.210, <i>P</i> &lt; 0.001). A multivariate linear regression analysis confirmed the strong relationship between higher HGI levels and lower MEEi, even after adjusting for several potential confounders, including sex, age, body mass index, waist circumference, smoking status, triglycerides, HDL cholesterol, 2-hour post-load glucose, glucose tolerance status, fasting insulin, HOMA-IR, hs-CRP, antihypertensive therapy, and lipid-lowering therapy.</p> Conclusions <p>These findings support the hypothesis that higher HGI values may affect myocardial mechano-energetic efficiency in non-diabetic individuals.</p> Graphical abstract <p></p>