Trends and Disparities in Mortality due to Diabetes Mellitus and Sepsis in the US Adults: 1999–2023

Background Diabetes mellitus (DM) increases susceptibility to infection and worsens outcomes in sepsis, a leading cause of preventable death. However, population‐level trends in sepsis‐related mortality among diabetic individuals in the United States (US) remain poorly characterised, especially in the context of the COVID‐19 pandemic. This study evaluates national patterns, temporal shifts, and demographic disparities in sepsis‐related mortality in diabetic patients from 1999 to 2023. Methods We conducted a retrospective analysis using the Centers for Disease Control and Prevention Wide‐ranging Online Data for Epidemiologic Research (CDC WONDER) Multiple Cause of Death database. Sepsis‐related deaths with co‐listed DM were extracted for US adults between 1999 and 2023. Age‐adjusted mortality rates (AAMRs) were calculated and Joinpoint regression was used to estimate annual percentage changes (APCs) and identify significant trends. Results A total of 483,207 sepsis‐related deaths occurred in individuals with DM during the study period. AAMRs declined significantly from 1999 to 2018 (APC: −1.22; p < 0.001), reversed sharply from 2018 to 2021 (APC: +18.14; p = 0.01), and declined again through 2023 (APC: −12.25; p < 0.001). Mortality was highest among older adults (AAMR: 32.63), males (9.72 vs. 7.80 in females), and non‐Hispanic Black and American Indian/Alaska Native populations (AAMRs: 17.94 and 17.92, respectively). Hispanic populations showed the steepest pandemic‐era increase (APC: +22.49) and subsequent decline (APC: −20.43). Rural areas consistently had higher AAMRs than urban areas (8.77 vs. 8.27), with sharper increases during the pandemic. State‐level disparities widened dramatically from 2021 to 2023, and regionally, the South and Midwest exhibited the highest and most persistent mortality burdens. Conclusion Sepsis‐related mortality in diabetic individuals in the US has undergone dynamic shifts over the past 25 years, punctuated by COVID‐19 era surges and shaped by deep‐rooted demographic, geographic, and structural inequities. These findings warrant integrated diabetes‐infection care models, early sepsis recognition, and equity‐driven interventions to reduce mortality.