S2681 Rising Mortality Due to Chronic Liver Disease and Diabetes in American Indians/Alaska Natives: A 1999-2020 Nationwide Analysis

Introduction: Chronic liver disease (CLD) is a major global health burden, and its overlap with diabetes is drawing growing attention due to shared pathophysiology. The rising prevalence of type 2 diabetes parallels increases in obesity and metabolic syndrome-key contributors to metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH). However, there is a lack of population-level data on the mortality burden associated with concurrent CLD and diabetes. In this study, we describe temporal and demographic patterns in CLD and diabetes deaths in the United States from 1999 to 2020. Methods: The CDC WONDER database was queried for records listing diabetes mellitus and CLD as underlying or contributing causes of death. Adults aged 25 years and above were included, and data were grouped by year, gender, race, and region. Age-adjusted mortality rates (AAMR) were calculated per 100,000 individuals. Joinpoint regression was used to calculate annual percent change (APC) and average annual percent change (AAPC) in AAMRs from 1999 to 2020. Results: Between 1999 and 2020, there were 75,883 deaths due to CLD and diabetes in the U.S. The AAMR increased from 0.71 in 1999 to 2.44 in 2020 (AAPC: 6.02, 95% CI: 5.51 to 6.53). A parallel trend was observed in men (AAPC: 5.91, 95% CI: 5.37 to 6.45) and women (5.68, 95% CI: 4.62 to 5.36), with men experiencing consistently higher AAMRs throughout the study period (overall AAMR men: 2.22; women: 0.92). Non-Hispanic American Indians/Alaska Natives had the highest AAMRs (overall AAMR: 5.39) and experienced the steepest overall increase in mortality until 2020 (AAPC: 6.78, 95% CI: 5.63 to 7.94), compared with other races. Urban regions had higher AAMRs (overall AAMR urban: 0.25; rural: 0.12) but experienced a significant decline in mortality from 1999 to 2020 (AAPC: -3.51, 95% CI: -4.56 to -2.45). Conclusion: From 1999 to 2020, CLD and diabetes mortality rose across most U.S. groups, with the sharpest increase and highest AAMRs in non-Hispanic American Indians/Alaska Natives individuals. Prior studies show higher diabetes and liver disease mortality in this population, likely due to systemic healthcare barriers. Broad behavioral and policy efforts are needed to reduce these disparities.