Global, regional and national burden of colon and rectum cancer attributable to high fasting plasma glucose: a systematic analysis for the Global Burden of Disease Study 2021

Ke Lu¹Gang Xu^2*

• ¹Hangzhou Xixi Hospital,Hangzhou Sixth People's Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
• ²Zhejiang Hospital, Hangzhou, China

Background: Colon and rectum cancer (CRC), as the third most common malignant cancer globally, imposes a substantial public health burden. Emerging evidence highlights hyperglycemia as an independent risk factor for CRC. Estimates of the global burden of high fasting plasma glucose (FPG)-derived CRC are lacking. Methods: We used Global Burden of Disease (GBD) 2021 data to analyze deaths and disability-adjusted life years (DALYs) of CRC attributable to high FPG across 204 countries or territories. GBD standard population was used to calculate age-standardized rates. Joinpoint regression identified temporal trends (1990–2021), while Bayesian age-period-cohort modeling projected future burdens (2022–2036). Health inequalities were assessed by stratifying the analyses according to the sociodemographic index (SDI). Results: Globally, high FPG-related CRC deaths increased from 31,907 (1990) to 82,421 (2021), with DALYs loss rising from 715,716 to 1,750,923. Age-standardized mortality rates (ASMR) and DALY rates (ASDR) increased by an average of 0.31% overall during study period but declined post-2019. High SDI regions bore the highest burden (ASMR: 1.33 per 100,000 persons-year; ASDR: 27.65 per 100,000 persons-year), yet trends stabilized, whereas low-middle SDI regions saw the sharpest rise (ASMR average annual percentage change [AAPC]: 1.82%; ASDR AAPC: 1.77%). Males predominated in the burden of CRC attributable to high FPG than females. Health inequality analysis showed that absolute differences in DALYs slightly increased (slope index of inequality of DALYs increase: 20.251 to 20.292), while relative differences decreased (concentration index of DALYs improvement: -0.344 to -0.294). Projections indicated a 6.1% decline in ASMR and a 1.8% decrease in ASDR by 2036. Conclusion: The escalating burden of high FPG-driven CRC underscores its growing role in CRC epidemiology, particularly in aging populations and regions undergoing rapid urbanization. Persistent gender and socioeconomic disparities necessitate region-tailored interventions, integrating diabetes management with CRC screening and equitable access to novel therapies. These findings advocate for prioritized metabolic risk control in global CRC prevention frameworks to mitigate future burdens.