A Human Cohort Data Validated Mechanistic Model Linking Psychosocial Stress to Type 2 Diabetes Risk

Abstract Psychosocial stress is associated with type 2 diabetes (T2D) related glycemic dysregulation, but quantitatively linking chronic stress to fasting glucose remains challenging. We developed a coupled endocrine metabolic model of stress hormone regulation and glycemic control. Depressive symptoms were quantified using the Center for Epidemiologic Studies Depression Scale (CESD) score, which served as a proxy for sustained stress drive. Using clinical data from the Multi Ethnic Study of Atherosclerosis (MESA) dataset, we identified a single physiologically plausible joint parameter range for glycemic regulation, stress coupling strength, and caloric intake drive. The model performed better for non diabetic individuals, whereas the proportion in the diabetes category was overestimated, most prominently in the depressed group. The findings were consistent on a reserved evaluation subset without refitting.