Intersecting Endocrine Pathways in Cardiomyopathy: The Role of Metabolic Burden in Structural Heart Disease

Background: Dilated cardiomyopathy (DCM) is a major contributor to heart failure-related morbidity and mortality. While type 2 diabetes mellitus (T2DM), obesity, and thyroid dysfunction are individually linked to cardiovascular disease, their combined effects on DCM remain poorly understood. Objective: To evaluate the independent and synergistic associations of diabetes (stratified by treatment), thyroid dysfunction, and obesity with the prevalence of DCM and 30-day hospital readmission. We further examined the utility of a composite Metabolic Burden Score for risk stratification. Methods: In this retrospective cohort study, electronic health record data from 1079 adult patients at a tertiary care center were analyzed. Multivariable logistic regression, including ridge regularization, was used to identify predictors of DCM. Endocrine phenotypes were stratified by diabetes and thyroid status. A Metabolic Burden Score (range: 0-3) based on diabetes, obesity, and thyroid dysfunction was developed and correlated with clinical outcomes. Results: DCM was diagnosed in 46% of the cohort. Non-insulin-treated diabetes (OR: 6.93; 95% CI: 3.78-12.73), hypothyroidism (OR: 1.78; 95% CI: 1.02-3.11), and male sex (OR: 2.33; 95% CI: 1.36-4.00) were independently associated with increased DCM risk. Obesity was not independently predictive but contributed to DCM prevalence when assessed within the Metabolic Burden Score. DCM prevalence increased across burden strata, reaching 50% in the high-risk group. Notably, the moderate-risk group had the highest 30-day readmission rate (42.8%). Conclusions: Non-insulin-treated diabetes and hypothyroidism are key metabolic drivers of DCM. A simple composite burden score offers a clinically useful tool for stratifying risk of DCM and early readmission. These findings support integrated endocrine-cardiac screening strategies to improve early identification and prevention of structural heart disease.