Background: SMD is a marker of myosteatosis that can be obtained from routine computed tomography (CT) imaging and could be used to screen patients for further frailty evaluation. But diabetes (DM) is linked with myosteatosis in men and SMD utility for patients with DM is unknown. We assessed SMD performance as a frailty screening tool in older adults with primarily gastrointestinal cancer and compared performance in patients stratified by sex and DM. Methods: We analyzed CARE Registry patients at baseline, a sample with mostly late-stage, gastrointestinal malignancies. Frailty and DM were captured in the CARE tool, a patient-reported geriatric assessment. SMD was calculated from CT scans at L3 vertebrae. Analyses were run for each sex and by DM status. We used linear regression to assess crude associations of SMD and frailty score. SMD performance in classifying frail status (vs. non-frail) was analyzed with 1) area under the receiver operating characteristic curves (AUC) and confidence intervals (CIs); and 2) sensitivity and specificity for sex-specific SMD quartile cut-offs (Q1, median, Q3). Cut-off performance was compared between patients with DM vs. without using differences in sensitivity and specificity and CIs. CIs were estimated with 2,000 bootstrap replicates. Results: The analytic sample (N=874; 27% DM, 32% frail) was 39% female with median age 68 years. For each sex-DM subset, regression results had negative slopes indicating that low SMD was associated with higher frailty score. AUCs for women with and without DM were 0.57 (95% CI 0.45-0.69) and 0.62 (0.54-0.70). AUCs for men with and without DM were 0.68 (0.59-0.77) and 0.58 (0.52-0.65). Sex-stratified sensitivity and specificity results are below. Median cut-offs had both sensitivity and specificity >0.50; Q3 cut-offs had higher sensitivity but low specificity. Conclusions: SMD could be used to pre-screen older adults with and without DM for further clinical frailty assessment. With high-sensitivity cut-offs (Q3), 13% to 26% of frail patients could be missed. Compared to other groups, SMD pre-screening for men with DM may miss the fewest frail patients but would produce many false-positives.