Abstract
BACKGROUND: The global burden of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) continues to rise, with these conditions significantly increasing risks of cardiovascular disease, disability, and mortality. Traditional Chinese Medicine (TCM) syndrome differentiation, a cornerstone of TCM practice, guides diagnosis and treatment by identifying patterns of disharmony. However, large-scale studies investigating TCM syndrome patterns in T2DM comorbid with MetS remain scarce. OBJECTIVE: This cross-sectional study aims to characterize TCM syndrome profiles in a population diagnosed with T2DM and MetS and evaluate their diagnostic relevance. METHODS: This cross-sectional study will enroll a cohort of 470 participants diagnosed with T2DM and MetS. All participants will undergo comprehensive assessments, including the Syndrome Differentiation Questionnaire for T2DM and MetS, demographic and anthropometric measurements, biochemical profiling (eg, fasting glucose, glycosylated hemoglobin, and lipid panel), dietary measurement (Food Frequency Questionnaire), physical activity measurement (International Physical Activity Questionnaire Short Form), sleep quality evaluation (Pittsburgh Sleep Quality Index), quality-of-life assessment (Audit of Diabetes-Dependent Quality of Life), stroke risk estimation (Framingham Stroke Risk Score), and retinal imaging. Latent class analysis will be used to identify the TCM syndrome patterns. Factor analysis will be employed to identify core TCM syndrome factors. Hierarchical cluster analysis will be performed to classify TCM syndrome elements, and logistic regression will examine associations between syndrome differentiation, metabolic parameters, lifestyle factors, and disease progression. RESULTS: This trial was registered on November 17, 2024. Participant recruitment for this study was initiated in November 2024. As of October 2025, more than 450 eligible participants have been enrolled and have completed data collection. Recruitment is scheduled to conclude on December 31, 2025. CONCLUSIONS: As the first large-scale clinical study to systematically characterize TCM syndrome differentiation in T2DM-MetS comorbidity, this research will establish syndrome profiles associated with metabolic parameters, lifestyle factors, and disease progression. The findings are expected to provide a framework for integrating TCM syndrome differentiation into chronic disease management, ultimately contributing to personalized treatment strategies and improved patient outcomes in integrative medicine. TRIAL REGISTRATION: ClinicalTrials.gov NCT06703684; https://clinicaltrials.gov/study/NCT06703684. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/86217.