GBD 2021 provides a comprehensive overview of disabilities and deaths caused by high BMI leading to CRC from 1990 to 2021 across different countries, ages, and genders. It estimated the incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and DALYs due to 369 diseases and injuries in 204 countries and regions. DALYs are a measure that combines years of YLLs and YLDs (15). We obtained the number of deaths and DALY data caused by high BMI leading to CRC in 204 countries and regions from the Global Health Data Exchange (GHDx) website,¹ age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) (16, 17). The 204 countries and regions were further divided into 21 regions based on their geographical location. Moreover, data analysis adopted a stratified approach, dividing age into 16 different groups, with 15 being 5-year age intervals (20–94 years, in 5-year intervals) and one being individuals aged 95 years and above.

We separately obtained SDI data for 1990–2021 from the GHDx. SDI is a good indicator of socioeconomic development related to health. It is a composite indicator of lag-distributed income per capita, the average educational attainment of the population aged 15 years and above, and the total fertility rate under the age of 25, ranging from 0 to 1. According to the SDI quintiles, 204 countries or regions were divided into five quintiles: low SDI (< 0.45), low-middle SDI (≥ 0.45 and < 0.61), middle SDI (≥ 0.61 and < 0.69), high-middle SDI (≥ 0.69 and < 0.80), and high SDI (≥ 0.80) (18, 19).

In this study, we analyzed the global, national burden of CRC caused by high BMI using the ASMR and ASDR (per 100,000 population) to reflect the actual situation of deaths and DALYs (20). To assess trends, we used the linear regression equation (y = α + βx + ε), where y represents the age-standardized rate (ASR), which refers to ASIR, ASMR, or ASDR and x represents the calendar year. The estimated annual percentage change (EAPC) was calculated as 100 × (exp(β) − 1), with its 95% confidence interval (CI) determined using the linear regression model. If the EAPC value and its 95% CI lower limit are both greater than 0, the ASR is considered to exhibit an increasing trend annually. If the EAPC value and its 95% CI upper limit are both less than 0, the ASR is considered to exhibit a decreasing trend annually. If the EAPC is close to 0, the ASR is considered stable (21). This method is widely used to quantify and summarize temporal changes in ASR (22, 23). Statistical analyses were performed using R software (version 4.4.1), with p-values <0.05 considered statistically significant.

To analyze the factors influencing the EAPC of the CRC burden related to high BMI, we used Pearson correlation analysis to examine the relationship between EAPC and ASR in 1990 and the relationship between EAPC and SDI scores in 2021, with data analysis performed using R software (version 4.4.1), two-tailed p < 0.05 was considered statistically significant.

To forecast the global disease burden of high BMI-related CRC from 2022 to 2035, we used an autoregressive integrated moving average (ARIMA) model. It forecasts future values based on past properties (limitations and prediction errors). The ARIMA model is defined by three parameters: p, d, and q, where p is the order of autoregression, q is the order of moving average, and d is the degree of difference. The ARIMA equation is Y t = α + ϕ 1 Y t − 1 + ϕ 2 Y t − 2 + … + ϕ p Y t − p + ε t + ϕ 1 ε t − 1 + … + ϕ q ε t − q '

where ϕ and θ are the autoregressive and moving average parameters, respectively. Y_t represents the differenced time series, and ε_t is the value of the random shock at time t. α is a constant (24, 25). After multiple tests, we identified the optimal model using the ARIMA (1,1,2) model to predict ASMR and ASDR for males and the ARIMA (2,0,0) model to predict ASMR and ASDR for females.

From 1990 to 2021, globally, the incidence of CRC revealed an increasing trend, with the number of cases increasing from 916,584 (95% UI 866,238–951,895) in 1990 to 2,194,143 (95% UI: 2,001,272–2,359,390) in 2021, with an EAPC of 0.15 (95% CI: 0.12–0.19) (Table 1). In 2021, among the quintiles of SDI, areas with high SDI had the highest ASIR, but its annual growth rate decreased (EAPC = −0.25; 95% CI: −0.35 to −0.16), while the region with the highest annual growth rate was the middle SDI (EAPC = 1.38; 95% CI: 1.3–1.46) (Table 1). At the regional level of GBD, the region with the fastest growth in ASIR was Central Latin America (EAPC = 2.05; 95% CI: 1.99–2.11), and the region with the largest annual decline in ASIR was High-income North America (EAPC = −0.8; 95% CI: −0.92 to −0.67) (Table 1).

Metabolic risk factors accounted for 16.6% of the global CRC deaths burden in 2021, of which high BMI and high fasting glucose were the main contributors, accounting for 9.5 and 7.9%, respectively. This represents a significant increase compared to 1990, indicating that metabolic risk factors, specifically high BMI, have become important contributors to CRC risk (Supplementary Figure S1A). The CRC DALYs burden attributable to metabolic risk factors mirrored the same pattern of the burden of deaths (Supplementary Figure S1B). In 2021, the CRC burden of deaths and DALYs attributable to metabolic risk factors was higher in high SDI, at 18.9 and 19.1%, with the most prominent contribution from high BMI, at 10.9 and 11.6% (Supplementary Figures S1A,B). Within the GBD region, high-income North America had the highest burden, with high BMI also playing a significant role (Supplementary Figures S1A,B). These findings clearly indicate that high BMI is the most important risk factor among the metabolic risks associated with CRC.

Over the past 32 years, the number of deaths due to CRC associated with high BMI has rapidly increased from 41,536 (95% UI: 17,666–67,379) in 1990 to 99,268 (95% UI: 42,956–157,949) in 2021, an increase of 139%. Meanwhile, ASMR has also increased, but the change is non-significant, rising from 1.14 per 100,000 population (95% UI: 0.48–1.86) in 1990 to 1.17 per 100,000 population (95% UI: 0.51–1.87) in 2021. The EAPC of ASMR was 0 (95% UI: −0.04 to 0.04), revealing a relatively stable trend (Table 2). From 1990 to 2021, the number of deaths from high BMI-related CRC increased significantly in men and women. The number of deaths among women was higher than that of men from 1990 to 2008; however, after 2008, the number of deaths among men surpassed that of women. Moreover, the ASMR in men has always been higher than that in women (Figure 1C). Although the number of deaths for men and women increased over the past 32 years, the ASMR for women revealed a significant downward trend (EAPC = −0.37, 95% CI: −0.42 to −0.31), while the ASMR for men depicted an upward trend (EAPC = 0.39, 95% CI: 0.36–0.42) (Table 2; Figure 1C).

Significant differences in the burden of CRC were caused by high BMI in regions with different SDI levels. In 2021, the high SDI regions had the highest number of deaths from high BMI-related CRC, with 36,530 (95% UI: 15,670–58,139), accounting for more than 35% of global cases (Table 2). Although the ASMR in high SDI regions decreased from 1.96 per 100,000 population (95% UI: 0.83–3.19) in 1990 to 1.68 per 100,000 population (95% UI: 0.73–2.66) in 2021, it was still significantly higher than that in other SDI regions. Over the past 32 years, the ASMR in low, low-middle, middle, and high-middle SDI regions revealed an upward trend, with the most significant increase in low-middle SDI regions (EAPC = 2.72, 95% CI: 2.65–2.79). Conversely, the ASMR in the high SDI regions significantly decreased (EAPC = −0.64, 95% CI: −0.69 to −0.59) (Table 2; Figure 1A).

At the GBD regional level, in 2021, East Asia had the highest number of deaths from high BMI-related CRC, with 20,371 (95% UI: 8,475–33,799), followed by Western Europe, with 18,026 (95% UI: 7,623–29,686). Central Europe had the highest ASMR, at 3.03 per 100,000 population (95% UI: 1.35–4.85). From 1990 to 2021, Southeast Asia had the most significant increase in ASMR (EAPC = 3.04, 95% CI: 2.93–3.15). Furthermore, Australasia experienced the largest decrease in ASMR (EAPC = −0.78, 95% CI: −0.86 to −0.71) (Table 2).

At the national level, in 2021, China had the highest number of deaths from CRC due to high BMI, with 19,418 (95% UI: 8,053–32,452), followed by the United States, with 11,402 (95% UI: 5,070–17,661). Kuwait had the largest increase in the number of deaths, with a 974.3% rise over 32 years. Among the 204 countries, only Austria saw a decrease in the number of deaths (Supplementary Table S1; Figure 2C). Hungary had the highest ASMR, at 3.79 per 100,000 population (95% UI: 1.72–6.19), followed by Slovakia and Uruguay, with ASMRs of 3.53 per 100,000 population (95% UI: 1.61–5.66) and 3.45 per 100,000 population (95% UI: 1.54–5.72), respectively (Supplementary Table S1; Figure 2A). Moreover, since 1990, Vietnam has experienced the most significant increase in ASMR (EAPC = 4.65, 95% CI: 4.49–4.81). Meanwhile, 30 countries revealed a downward trend in ASMR, with Austria experiencing the most significant decrease (EAPC = −1.86, 95% CI: −1.92 to −1.8) (Supplementary Table S1; Figure 2E).

From 1990 to 2021, the number of DALYs due to high BMI-related CRC increased from 1,015,042 (95% UI: 429,787–1,631,974) in 1990 to 2,364,664 (95% UI: 1,021,594–3,752,340) in 2021 globally, an increase of 133%. The ASDR also rose from 25.54 per 100,000 population (95% UI: 10.83–41.2) in 1990 to 27.33 per 100,000 population (95% UI: 11.8–43.37) in 2021, with an EAPC of 0.12 (95% CI: 0.08–0.16) (Table 3). The trend of DALYs due to high BMI-related CRC in both men and women was similar to the trend in mortality. In 1990, the number of DALYs in women was higher than in men, but by 1999, the number of DALYs in men surpassed that in women, and the gap continued to widen (Figure 1D). Additionally, the ASDR for men increased from 26.42 per 100,000 population (95% UI: 10.97–42.88) in 1990 to 31.09 per 100,000 population (95% UI: 13.36–49.47) in 2021, revealing a significant upward trend (EAPC = 0.48, 95% CI: 0.45–0.51). In contrast, the ASDR for women decreased from 24.73 per 100,000 population (95% UI: 10.59–39.99) in 1990 to 23.96 per 100,000 population (95% UI: 10.36–37.75) in 2021, exhibiting a significant downward trend (EAPC = −0.26, 95% CI: −0.31 to −0.2) (Table 3; Figure 1D).

In terms of SDI, from 1990 to 2021, the number of DALYs and ASDR due to high BMI-related CRC in high SDI regions has always been the highest. However, the ASDR in high SDI regions decreased from 44.94 per 100,000 population (95% UI: 19.27–72.19) in 1990 to 40 per 100,000 population (95% UI: 17.48–62.93) in 2021, with an EAPC of −0.48 (95% CI: −0.52 to −0.43). This is the only SDI region where the ASDR exhibited a downward trend. The ASDR in other SDI regions revealed an upward trend, with the most significant increase in low-middle SDI regions (EAPC = 2.69, 95% CI: 2.63–2.76) (Table 3; Figure 1B).

For the GBD regions, in 2021, East Asia recorded the largest number of DALYs owing to high BMI-related CRC, with 529,352 cases (95% UI: 219,133–886,681). Central Europe had the most significant ASDR at 68.94 per 100,000 population (95% UI: 30.82–110.6). Over the past 32 years, 17 out of 21 GBD regions revealed an upward trend in ASDR, with Southeast Asia experiencing the most notable increase (EAPC = 2.84, 95% UI: 2.72–2.97). Conversely, Western Europe, high-income North America, Central Asia, and Australasia exhibited a downward trend in ASDR, with Australasia having the most pronounced decrease (EAPC = −0.94, 95% CI: −1.02 to −0.85) (Table 3).

From a national perspective, in 2021, China had the highest number of DALYs due to high BMI-related CRC, with 507,316 (95% UI: 209,264–853,770). From 1990 to 2021, among 204 countries, the number of DALYs increased rapidly in most countries, while only Austria, Germany, and the Czech Republic observed a decrease in DALYs, with reductions of 13.9, 5.6 and 4.8%, respectively (Supplementary Table S2; Figure 2D). Hungary exhibited the highest ASDR, at 92.03 per 100,000 population (95% UI: 41.88–149.98), followed by Slovakia, at 82.15 per 100,000 population (95% UI: 37.4–131.78) (Supplementary Table S2; Figure 2B). Notably, more than half of the countries have seen an increase in the ASDR EAPC. Vietnam (EAPC = 4.74, 95% CI: 4.54–4.94), Lesotho (EAPC = 4.7, 95% CI: 4.15–5.25), and Zimbabwe (EAPC = 4.11, 95% CI: 3.45–4.78) had the largest increases, which may indicate severe health challenges in these countries. Conversely, the ASDR in a few countries, such as the Czech Republic (EAPC = −1.81, 95% CI: −1.99 to −1.63) and Germany (EAPC = −1.65, 95% CI: −1.77 to −1.54), exhibited the most significant decrease (Supplementary Table S2; Figure 2F).

In 2021, the total number of deaths due to high BMI-related CRC increased for both men and women, with male deaths reaching 50,976 and female deaths reaching 48,292 (Table 2). The number of deaths for men and women exhibited a synchronous pattern, first increasing and then decreasing with age, peaking at 70–74 years. However, male deaths were not always higher than female deaths. Before the age of 80–84 years, male deaths were significantly higher than female deaths, but this trend reversed after the age of 80–84 years (Figure 3A). The trend in mortality rates was similar, with age-specific mortality rates in men and women increasing with age. Female mortality rates significantly exceeded male rates at ages 95+, whereas male mortality rates were higher than female rates before this age range (Figure 4A). The age-specific trend for DALYs was similar to that for mortality, but the peak number of DALYs occurred in the 65–69 age group (Table 3; Figure 3B). The age-specific DALY rates for men and women increased significantly with age, but the DALY rate for men began to decline after 90–94 years of age (Figure 4B). Globally, from 1990 to 2021, age-specific mortality rates for men and women in the 20–49 and 95+ age groups increased, with the 25–29 age group experiencing the fastest growth in mortality rates. Among men, from 1990 to 2021, mortality rates increased across almost all age groups, with the 25–29 age group exhibiting the most significant increase. In contrast, among women, mortality rates decreased in the 50–94 years age group, with the 65–69 years age group revealing the most significant decrease (Figure 4C).

In 2021, across the five SDI regions, age-specific mortality rates due to high BMI-related CRC generally increased with age. Age-specific mortality rates in high and middle-high SDI regions were significantly higher than in other regions (Figure 3C)The age-specific DALYs rate was similar to the mortality rate, with the difference that the DALYs rates in the high, middle, low-middle, and low SDI regions depicted a declining trend at ages 80–84 (Figure 3D). The peak age-specific mortality and DALY rates in most regions occurred after the age of 90. Similarly, from 1990 to 2021, the age-specific mortality rates in the low, low-middle, and middle SDI regions increased significantly across all age groups. Among the five SDI regions, the low-middle SDI regions had the largest increase in mortality rates, followed by the middle SDI regions (Figure 4D). In high SDI regions, age-specific mortality rates in the 50–94 age group decreased annually, with the 70–74 age group experiencing the largest decline. In high-middle SDI regions, only the 50–54 age group’s age-specific mortality rate decreased, while mortality rates in relatively younger and older age groups increased (Figure 4D).

Across the 21 GBD regions globally, from 1990 to 2021, the ASMR of high BMI-related CRC exhibited an inverted V-shaped nonlinear relationship with the SDI (ρ = 0.739, p < 0.001), peaking at an SDI of approximately 0.75. When SDI < 0.75, the ASMR increased gradually, whereas when SDI > 0.75, the ASMR declined rapidly (Figure 5A). A comparable relationship was also observed between the ASDR and SDI (Figure 5B). Among 204 countries worldwide, the ASMR of high BMI-related CRC in 1990 was significantly negatively correlated with EAPC from 1990 to 2021 (ρ = −0.693, p < 0.001) (Figure 6A), The ASDR in 1990 exhibited the same trend as the EAPC from 1990 to 2021 (ρ = −0.672, p < 0.001) (Figure 6B). The relationship between the EAPC of high BMI-related CRC and the SDI in 2021 exhibited an inverted “U” shape. When the SDI was below 0.5, a positive correlation was observed. When the SDI ≥ 0.5, both the EAPC of ASMR (ρ = −0.487, p < 0.001) and the EAPC of ASDR (ρ = −0.485, p < 0.001) were negatively correlated with the SDI (Figures 7A,B). The SDI for 204 countries from 1990 to 2021 are listed in Supplementary Table S3.

According to the ARIMA model, from 2022 to 2035, the burden of high BMI-related CRC in males will continue to rise, with the ASMR increasing from 1.33 per 100,000 population (95% UI: 0.57–2.13) in 2021 to 1.4 per 100,000 population (95% UI: 1.33–1.47) in 2035, and the ASDR increasing from 31.09 per 100,000 population (95% UI: 13.36–49.47) in 2021 to 33.07 per 100,000 population (95% UI: 31.35–34.79) in 2035 (Table 4; Figures 8A,B). In females, both the ASMR and ASDR of high BMI-related CRC exhibited a slightly increasing trend and gradually stabilized (Table 4; Figures 8C,D).