Among 562 metabolic syndrome patients from the PREDIMED-Plus trial tracked over five years, diabetes status independently predicted worsening subclinical cardiac biomarkers regardless of glycemic control quality. Cross-sectionally, higher HbA1c correlated inversely with NT-proBNP (β=−0.16) and directly with high-sensitivity troponin T (hsTnT, β=0.08). Critically, longitudinal analysis showed that well-controlled diabetics (HbA1c <7%) experienced significantly greater rises in both hsTnT (β=0.10) and the cardiac fibrosis marker PICP (β=0.14) compared to normoglycemic participants, while inflammatory markers hsCRP and oxidative-stress marker 3-nitrotyrosine showed no consistent signal.
The finding that adequate glycemic control does not fully arrest subclinical myocardial injury and fibrosis progression challenges the clinical assumption that keeping HbA1c below 7% sufficiently neutralizes cardiovascular risk in diabetics. It aligns with emerging evidence that non-glycemic mechanisms — including low-grade inflammation, autonomic dysfunction, and metabolic cardiomyopathy — independently drive cardiac remodeling in type 2 diabetes. The PICP elevation is particularly notable: rising procollagen I synthesis signals extracellular matrix turnover and early fibrosis, a process largely invisible to standard lipid or glucose panels.
Limitations are meaningful: the cohort is older, Spanish, and metabolic-syndrome-defined, limiting generalizability; the normoglycemic reference group is small (n=50); and effect sizes are modest. As a preprint not yet peer-reviewed, these results could shift under editorial scrutiny. Still, the study makes a pragmatic case for routine cardiac biomarker monitoring in diabetic patients even when glucose targets are met — an incremental but clinically actionable contribution.
