Diabetes-Specific Serum Calcium Thresholds for Mortality Risk: A NHANES Nutritional Epidemiology Study

This retrospective cohort study aimed to characterize diabetes-stratified associations between serum calcium levels and all-cause, cardiovascular (CVD), and cancer mortality, addressing a critical gap in nutritional epidemiology. Leveraging the National Health and Nutrition Examination Survey (NHANES) database, we conducted Cox proportional hazards regression with restricted cubic splines to model non-linear calcium-mortality relationships. Mediation analysis was conducted in diabetes. The T2DM group presented a J-shaped relationship, with relatively stable and low mortality risk at lower calcium concentrations, followed by a significant increase at higher concentrations. In contrast, the group without diabetes exhibited a U-shaped relationship, indicating that both low and high serum calcium levels are associated with increased mortality risk, with an optimal range in the middle where the risk is minimized. Mediation analysis indicated that, in individuals with T2DM, the relationship between serum calcium levels and mortality was partially mediated by markers of renal function and total cholesterol. Our findings support personalized calcium monitoring as a cost-effective strategy in diabetic care. Serum calcium thresholds for mortality risk differ fundamentally by diabetes status, underscoring the need for precision nutrition strategies. Integration of calcium monitoring into routine diabetic care-particularly targeting high-risk subgroups-may mitigate mortality.