Introduction Diabetes mellitus (DM) encompasses metabolic disorders characterized by elevated blood sugar. This study aimed to evaluate the prevalence and associated metrics of DM in the Rio Grande Valley (RGV), a low-income and medically underserved region in the United States, and compare these metrics to the national averages from 2012 to 2022. Methods A retrospective cross-sectional analysis was conducted using publicly accessible data from the Centers for Medicare and Medicaid Services (CMS). Metrics analyzed included DM prevalence, average principal cost, rates of emergency department visits, hospitalizations, screenings, and prevalence of obesity. Data from the RGV counties were compared to national averages using Mann-Whitney U tests, with a p-value of <0.05 considered significant. Results From 2012 to 2022, DM affected patients in the RGV (43.95%) at significantly higher rates than the national average (26.73%) (p < 0.001). Obesity prevalence in the RGV was at higher rates than the national average (24.41% vs. 15.55%, p < 0.01). The screening rates of DM exceeded the national average (10.64% vs. 5.09%, p < 0.001). The average principal cost for patients in the RGV ($1,920.45) to treat DM was significantly greater than the national average principal cost ($859.64) (p < 0.001). The RGV also reported higher rates of ED visits (16.82 vs. 8.82 per 1,000 beneficiaries, p < 0.001) and hospitalizations (7.75 vs. 3.82 per 1,000 beneficiaries, p < 0.001). Conclusion The RGV exhibits significantly higher rates of DM and DM-associated metrics compared to the national averages, highlighting substantial public health disparities., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Gaddis et al.)