S2468 Rising Tide in America: US Burden and Mortality Trends of Primary Liver Cancer Attributable to Fasting Plasma Glucose (Type 2 Diabetes): 1990-2021

Introduction: Primary liver cancer (PLC) is a major cause of cancer mortality in the United States, with its burden increasingly driven by metabolic risk factors such as type 2 diabetes mellitus (T2DM). Elevated fasting plasma glucose (FPG) has emerged as a significant and modifiable contributor to hepatocarcinogenesis. However, the long-term trends of PLC burden attributable to high fasting glucose in the U.S. remain under-characterized. to analyze U.S. trends in disability-adjusted life years (DALYs), mortality, and incidence rates of primary liver cancer attributable to high fasting plasma glucose from 1990 to 2021 using the Global Burden of Disease (GBD) database. Methods: Data were extracted from the GBD database focusing on U.S. estimates of PLC attributable to high fasting plasma glucose from 1990 to 2021. Metrics included DALYs (number and rate per 100,000), deaths (absolute number, percent, and rate per 100,000), and age-standardized incidence and mortality rates. Trends were evaluated using visual analysis and average annual percent change (AAPC). Age-standardized rates were prioritized for cross-year comparability. Results: In the U.S., DALYs attributable to high fasting plasma glucose rose from approximately 5,000 in 1990 to over 35,000 in 2021, with the steepest increases occurring after 2005. The DALY rate per 100,000 increased from around 2 to over 13. Deaths from PLC attributable to high FPG climbed from roughly 200 in 1990 to over 1,600 in 2021. The age-standardized death rate increased from approximately 0.1 to nearly 0.6 per 100,000 population. The proportion of PLC deaths attributable to high FPG nearly doubled, from ∼4% in 1990 to ∼8.5% in 2021. Both age-adjusted mortality and incidence trends showed consistent upward trajectories, indicating a growing metabolic contribution to liver cancer burden in the U.S. Conclusion: The burden of primary liver cancer attributable to high fasting plasma glucose has risen significantly in the United States over the past 3 decades. These findings highlight the urgent need for national public health strategies focused on diabetes prevention and glycemic control to mitigate liver cancer risk.