National trends and demographic disparities in mortality among adults with hepatocellular carcinoma and diabetes mellitus in the United States (1999–2020).

e16168 Background: Hepatocellular carcinoma (HCC) is a growing public health concern in the United States, particularly among individuals with diabetes mellitus (DM). The coexistence of DM can accelerate hepatic dysfunction, worsen clinical outcomes, and elevate HCC-related mortality risk. However, national trends in HCC and DM-related mortality, along with the demographic disparities remain insufficiently explored. Methods: We utilized CDC WONDER data from 1999 to 2020 to examine U.S. adults aged ≥25 years whose death certificates included both HCC (ICD-10 C22) and DM (ICD-10 E10–E14) as either underlying or contributing causes of death. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated overall and stratified by sex, age group, race/ethnicity, and state. Temporal trends were assessed using Joinpoint regression to estimate annual percent change (APC), with statistical significance defined as p≤0.05. Results: Overall, HCC among DM patients accounted for 33,955 deaths in the adult U.S. population from 1999 to 2020. The overall AAMR rose from 0.46 to 0.98, corresponding to a significant APC of 3.19% (95% CI: 2.96–3.50%, p < 0.001). Males experienced an increase in AAMR from 0.66 to 1.50 (APC 3.30%; 95% CI: 3.06–3.62), while females had rates rising from 0.32 to 0.55 (APC 2.41%; 95% CI: 1.97–2.96). Older adults accounted for the highest mortality burden (AAMR: 2.67), whereas middle-aged adults demonstrated an AAMR of 0.51. AAMRs were highest among American Indian or Alaska Native and White individuals. The American Indian or Alaska Native population exhibited the fastest rising trend (APC: 6.90%; 95% CI: 3.82–9.83). Significant increases were also observed among White (APC: 3.59%; 95% CI: 3.05–3.98), Hispanic or Latino (APC: 2.03%; 95% CI: 1.60–2.64), Black or African American (APC: 1.95%; 95% CI: 1.11–3.05), and Asian or Pacific Islander (APC: 1.40%; 95% CI: 0.48–2.76) populations. Non-metropolitan areas showed a more pronounced increase in mortality compared to metropolitan areas. Regionally, the West and South experienced the largest increases in deaths, while Texas, California, and Hawaii had the highest state-level rates. Conclusions: HCC mortality among DM patients in the United States nearly doubled from 1999–2020, with substantial disparities across sex, age, race/ethnicity, geographic region, and urban–rural status. These findings underscore the need for targeted prevention, early detection, and intervention strategies in high-risk populations to mitigate the growing burden of HCC in patients with diabetes.