NT-proBNP–echocardiographic discordance in type 2 diabetes: links with adiposity and left atrioventricular coupling
TL;DR
In hospitalized adults with T2DM, NT-proBNP below 125 pg/mL did not fully exclude prespecified structural or diastolic echocardiographic abnormalities, and these findings support complementary echocardiographic phenotyping when NT-proBNP concentrations appear reassuring.
Abstract
Background NT-proBNP is widely used to support the exclusion of heart failure, but its concentration may be lower in individuals with excess adiposity and insulin resistance. Whether NT-proBNP below 125 pg/mL excludes early echocardiographic abnormalities in patients with type 2 diabetes mellitus (T2DM) remains uncertain. Methods This retrospective cross-sectional study included 191 adults with T2DM hospitalized between May 2024 and November 2025. NT-proBNP measurement and echocardiography were performed within 48 hours. NT-proBNP was categorized at 125 pg/mL and compared with two prespecified echocardiographic outcomes: Layer 1, an operational definition of diastolic dysfunction informed by the 2025 American Society of Echocardiography recommendations and based on consistently available variables; and Layer 2, a composite structural and/or diastolic abnormality. Associations of body mass index (BMI) and the triglyceride-glucose index (TyG) with left atrial and atrioventricular coupling phenotypes were assessed among participants with NT-proBNP <125 pg/mL. Results Among the 191 participants, 153 had NT-proBNP <125 pg/mL. Layer 1 abnormality was present in 17 of these participants (11.1%), whereas Layer 2 abnormality was present in 38 (24.8%). Agreement between NT-proBNP classification and Layer 1 and Layer 2 outcomes was 79.6% (Cohen κ=0.326) and 73.3% (Cohen κ=0.328), respectively. In the NT-proBNP <125 pg/mL subgroup, participants with BMI ≥24 kg/m² had higher average E/e′, left atrial volume index, left atrioventricular coupling index, and left atrial stiffness index, and lower left atrial reservoir strain, than those with BMI <24 kg/m². After multivariable adjustment, overweight/obesity was associated with Layer 1 abnormality (odds ratio 3.16, 95% confidence interval 1.03–9.74; P = 0.045) and Layer 2 abnormality (odds ratio 4.15, 95% confidence interval 1.66–10.39; P = 0.002). In mutually adjusted linear models, BMI and TyG were independently associated with higher left atrioventricular coupling index, while TyG was associated with lower left atrial reservoir strain and higher left atrial stiffness index. Conclusions In hospitalized adults with T2DM, NT-proBNP below 125 pg/mL did not fully exclude prespecified structural or diastolic echocardiographic abnormalities. Higher BMI was associated with adverse left atrioventricular coupling, whereas a higher TyG index showed more consistent associations with left atrial functional phenotypes. These findings support complementary echocardiographic phenotyping when NT-proBNP concentrations appear reassuring.