Diabetes and glycemic control as predictors of cardiovascular disease risk biomarkers among people with the metabolic syndrome: a longitudinal analysis

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among individuals with diabetes, where risk remains elevated even with good glycemic control. Cardiac biomarkers such as N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), high sensitivity C Reactive Protein (hsCRP), Procollagen Type I Carboxy-Terminal Propeptide (PICP), and 3-Nytrotirosine (3-NT) may capture subclinical cardiac stress and injury beyond traditional risk measures. Methods: We analyzed 562 participants from the PREDIMED-Plus trial with data on diabetes status, glycosylated hemoglobin (HbA1c), and cardiovascular biomarkers. At baseline, participants were categorized as having normoglycemia (HbA1c <5.7%; n=50), prediabetes (HbA1c ≥5.7 to <6.5%; n=353), diabetes with well-controlled glycemia (HbA1c <7%; n=127), or diabetes with poorly controlled glycemia (HbA1c ≥7%; n=32). Cardiac biomarkers assessed at baseline, 3 years, and 5 years included NT-proBNP, hsTnT, hsCRP, PICP, and 3-NT. Mixed models, adjusted for demographic, clinical, and lifestyle covariates, were used to examine cross-sectional and longitudinal associations. Results: Cross-sectionally, higher HbA1c was inversely associated with NT-proBNP (β = -0.16, 95% CI: -0.29, -0.04) and directly associated with hsTnT (β = 0.08, 95% CI: 0.02, 0.14), particularly among those with poorly controlled diabetes. No consistent associations were observed for hsCRP, PICP, or 3-NT. Longitudinally, baseline differences in diabetes status were not significantly related to biomarker changes. However, compared to normoglycemic participants, those with well-controlled diabetes showed higher increases in hsTnT (β = 0.10, 95% CI: 0.02, 0.19) and PICP (β = 0.14, 95% CI: 0.01, 0.28). Conclusion: Even with adequate glycemic control, individuals with diabetes may experience progression of subclinical cardiac damage and fibrosis. Incorporating cardiac biomarkers into risk assessment may improve early identification of CVD risk in high-risk populations.