Background CT biomarkers both inside and outside the pancreas can potentially be used to diagnose type 2 diabetes mellitus. Previous studies on this topic have shown significant results but were limited by manual methods and small study samples. Purpose To investigate abdominal CT biomarkers for type 2 diabetes mellitus in a large clinical data set using fully automated deep learning. Materials and Methods For external validation, noncontrast abdominal CT images were retrospectively collected from consecutive patients who underwent routine colorectal cancer screening with CT colonography from 2004 to 2016. The pancreas was segmented using a deep learning method that outputs measurements of interest, including CT attenuation, volume, fat content, and pancreas fractal dimension. Additional biomarkers assessed included visceral fat, atherosclerotic plaque, liver and muscle CT attenuation, and muscle volume. Univariable and multivariable analyses were performed, separating patients into groups based on time between type 2 diabetes diagnosis and CT date and including clinical factors such as sex, age, body mass index (BMI), BMI greater than 30 kg/m2, and height. The best set of predictors for type 2 diabetes were determined using multinomial logistic regression. Results A total of 8992 patients (mean age, 57 years ± 8 [SD]; 5009 women) were evaluated in the test set, of whom 572 had type 2 diabetes mellitus. The deep learning model had a mean Dice similarity coefficient for the pancreas of 0.69 ± 0.17, similar to the interobserver Dice similarity coefficient of 0.69 ± 0.09 (P = .92). The univariable analysis showed that patients with diabetes had, on average, lower pancreatic CT attenuation (mean, 18.74 HU ± 16.54 vs 29.99 HU ± 13.41; P < .0001) and greater visceral fat volume (mean, 235.0 mL ± 108.6 vs 130.9 mL ± 96.3; P < .0001) than those without diabetes. Patients with diabetes also showed a progressive decrease in pancreatic attenuation with greater duration of disease. The final multivariable model showed pairwise areas under the receiver operating characteristic curve (AUCs) of 0.81 and 0.85 between patients without and patients with diabetes who were diagnosed 0-2499 days before and after undergoing CT, respectively. In the multivariable analysis, adding clinical data did not improve upon CT-based AUC performance (AUC = 0.67 for the CT-only model vs 0.68 for the CT and clinical model). The best predictors of type 2 diabetes mellitus included intrapancreatic fat percentage, pancreatic fractal dimension, plaque severity between the L1 and L4 vertebra levels, average liver CT attenuation, and BMI. Conclusion The diagnosis of type 2 diabetes mellitus was associated with abdominal CT biomarkers, especially measures of pancreatic CT attenuation and visceral fat. © RSNA, 2022 Online supplemental material is available for this article.