ObjectiveThis study examined the association between the prevalence of cardiometabolic disease and fat-enlarged lymph nodes (LNs), identified on digital screening mammography.MethodsA cross-sectional study on 834 women presenting for full-field digital screening mammography was conducted. The status of fat-enlarged LNs was assessed based on the size and morphology of axillary LNs from the mammograms. The prevalence of cardiometabolic disease, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, high blood glucose, cardiovascular disease, stroke, and non-alcoholic fatty liver disease, were retrieved from the electronic medical records.ResultsFat-enlarged axillary LNs were associated with a high prevalence of T2DM among all women (adjusted odds ratio: 3.92, 95% CI: [2.40, 6.60], p-value < 0.001), and in subgroups of women with and without obesity. Utilizing the status of fatty LNs improved the classification of T2DM status in addition to age and BMI (1.4% improvement in the area under the receiver operating characteristic curve).ConclusionFat-enlarge axillary LNs visualized on screening mammograms were associated with the prevalence of T2DM. If further validated with larger datasets from external institutions, fat-enlarged axillary LNs may become a novel imaging biomarker in clinical practice to improve the risk assessment of T2DM for women with screening mammography.