Microstructural analysis of the human ventricular myocardium in subjects with Type-II Diabetes

Prolonged onset of Type-II Diabetes is known to induce structural and mechanical remodeling in the ventricular myocardium or heart wall. This study aimed to compare the microarchitecture, fiber organization, and stiffness of left ventricular heart tissues from diabetic vs non-diabetic donor myocardium tissues. Myocardial tissue samples were obtained from six human donors (three diabetic, three non-diabetic) and processed using cryotome sectioning, tissue clearing, and staining protocols. Light sheet fluorescence microscopy was employed to visualize vascular and extracellular matrix components using lectin, propidium iodide, and fast-green staining. Scanning electron microscopy (SEM) was used to assess fibril morphology, and rheological testing was conducted to determine tissue stiffness. Light sheet microscopy revealed disrupted and reduced vascular networks in diabetic tissue samples, accompanied by decreased cellularity and increased fiber content. SEM analysis showed that fibrils in diabetic myocardium were generally longer and more variable in length, suggesting altered extracellular matrix remodeling. Rheological testing demonstrated that diabetic tissues had higher elastic modulus, and complex viscosity, implying increased stiffness and reduced compliance. Collectively, these substantial changes in myocardial architecture include excessive fiber deposition, disrupted vasculature, and enhanced tissue stiffness. These alterations are consistent with features of cardiac disease pathologies and underscore the potential of imaging and mechanical profiling as diagnostic tools for early detection and therapeutic targeting of diabetic cardiac remodeling. This pilot study is limited by its small sample size (n = 3 per group) and is intended as a feasibility assessment, providing a roadmap for high-throughput screening of larger sample sets. Findings represent preliminary trends rather than definitive conclusions, and larger-scale studies will be required to validate these observations.