Temporal patterns in mortality from type 2 diabetes and digestive system cancers-an epidemiological analysis of the US population from 1999 to 2023

Abstract

Objective

Type 2 Diabetes Mellitus (T2DM) is closely associated with digestive organ malignancies; however, population-level data remains scarce regarding mortality trends where both conditions coexist. This study aims to assess the national trends and disparities in mortality rates for deaths in which both T2DM and digestive organ malignancies were listed on the death certificate among middle-aged and elderly individuals in the United States from 1999 to 2023.

Materials and methods

Using the CDC WONDER database, this study analyzed deaths among U.S. individuals aged ≥ 45 years from 1999 to 2023. Deaths were included if both T2DM (ICD-10: E11) and digestive organ malignancies (ICD-10: C15-C26) were listed on the death certificate as either underlying or contributing causes. The crude mortality rate (CDR) and age-adjusted mortality rate (AAMR) per 100,000 people were calculated. Joinpoint regression analysis was used to estimate the average annual percent change (AAPC) and identify significant trend shifts.

Results

A total of 94,676 deaths involving both T2DM and digestive organ malignancies were identified. The overall AAMR increased significantly from 1.82 (95%CI 1.74–1.91) to 4.93 (95%CI 4.82–5.04) per 100,000, with an AAPC of + 4.13% (95%CI 3.83–4.56, P < 0.05). Sensitivity analysis confirmed the robustness of this upward trend, with a significant acceleration after 2013 (APC + 7.07%, 95%CI 5.91–8.60, P < 0.05). Significant disparities were observed across all subgroups: males had consistently higher AAMR than females (AAMR 6.80 vs 3.47; AAPC + 4.39% vs + 3.91%, all P < 0.05); the Hispanic/Latino population had the fastest growth (AAPC + 5.56%, P < 0.05); the West region showed the most pronounced increase (AAPC + 6.58%, P < 0.05); and rural areas had persistently higher AAMR than urban metropolitan areas (AAMR 5.79 vs 3.90, P < 0.05). While crude mortality was highest in adults aged ≥ 85 years, the 45–54 age group exhibited the steepest annual increase (AAPC + 7.4%, P < 0.05).

Conclusions

Between 1999 and 2023, mortality involving both T2DM and digestive malignancies in the U.S. rose sharply, with significant acceleration in the last decade. The pronounced disparities across gender, race, and geography—particularly the heavy burden in rural and Hispanic populations—necessitate targeted public health interventions and integrated metabolic-oncological screening protocols to mitigate these increasing burdens.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12889-026-27253-z.

Introduction

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and relative insulin secretion deficiency [1, 2]. Its global prevalence is continuously increasing, posing significant public health concerns [3]. As the prevalence of T2DM rises globally, the association between T2DM and various cancers, especially gastrointestinal (GI) cancers such as pancreatic, colorectal, liver, and gastric cancers, has garnered increasing attention [4–6]. Epidemiological studies have shown that T2DM is not just a metabolic disorder, but also an independent risk factor for several malignant tumors [7, 8]. The link between T2DM and GI cancers is well-established, with mechanisms involving hyperinsulinemia, chronic inflammation, obesity, and dysregulated lipid metabolism contributing to the increased cancer risk. However, despite the clear association, there is limited research on the changes in mortality rates for both T2DM and digestive cancers simultaneously.

In the United States, T2DM is associated with significantly increased mortality rates, not only due to its direct effects on cardiovascular and renal health but also due to its role in the development of various cancers. According to recent data from the Centers for Disease Control and Prevention (CDC), the prevalence of T2DM in the U.S. has been steadily rising, with over 34 million adults diagnosed, and nearly 1 in 3 adults at risk due to prediabetes [9]. This increased prevalence has been linked to higher incidences of GI cancers, particularly colorectal and pancreatic cancers. For instance, the incidence of colorectal cancer in diabetic patients is significantly higher, with studies suggesting a 20–30% increased risk compared to non-diabetic individuals [10]. Despite advances in the management of T2DM, mortality from both diabetes and GI cancers remains high, especially among certain demographic groups, including older adults, racial minorities, and those with low socioeconomic status.

While existing studies have shown that T2DM increases the risk of developing GI cancers and contributes to higher mortality, the impact of T2DM on cancer-related mortality in a contemporary setting, especially in light of recent improvements in diabetes management and oncological care, is less well understood. This study aims to fill this gap by analyzing temporal trends in mortality associated with both T2DM and GI cancers across various demographic and geographic groups. Using the CDC WONDER database from 1999 to 2023, this study will clarify trends in mortality and quantify disparities across gender, race, urbanization levels, and geographic regions. Identifying these high-risk clusters is essential for developing targeted screening protocols, optimizing clinical interventions, and formulating equitable public health policies that address the evolving needs of T2DM patients at risk for GI cancers.

Our study will contribute to the existing body of literature by providing updated and comprehensive data on mortality trends in T2DM and GI cancers, highlighting regional and demographic disparities, and offering insights into potential interventions to reduce these mortality rates.

Materials and methods

This descriptive study analyzed mortality trends using data extracted from death certificates available through the CDC WONDER database. The objective was to assess mortality rates related to T2DM and malignant neoplasms of the digestive organs in adults aged ≥ 45 years from 1999 to 2023. This specific age threshold was selected as both T2DM and digestive malignancies exhibit a significantly higher prevalence and clinical impact in the middle-aged and elderly populations. Data were obtained from the Multiple Cause of Death (MCD) public use dataset, which provides nationwide mortality information encompassing all 50 U.S. states and the District of Columbia. Mortality attributed to primary T2DM was identified using the ICD-10 code E11, and deaths associated with malignant neoplasms of digestive organs were classified using ICD-10 codes C15–C26. Cases that listed both conditions on the death certificate were included in the analysis. A sensitivity analysis was conducted including deaths in which malignant neoplasms of digestive organs were listed as the underlying cause of death and T2DM as a contributing cause, using the Multiple Cause of Death (MCD) public-access dataset. Since the analysis relied exclusively on de-identified, publicly accessible federal data, it was exempt from institutional review board (IRB) evaluation. Methodological transparency and rigor were maintained by complying with the STROBE guidelines for observational research.

Mortality rates were categorized according to key demographic and geographic variables, including sex, race, census region, and urbanization level. Race and ethnicity were classified as Hispanic/Latino, non-Hispanic (NH) white, and NH Black/African American, consistent with the categorization conventions employed in previous analyses of the CDC WONDER database [11]. Urban–rural designations adhere to the National Center for Health Statistics (NCHS) classification system, which is based on the 2013 U.S. Census data. Under this system, urban areas include large metropolitan areas (population ≥ 1 million) and medium/small metropolitan areas (population between 50,000 and 999,999), whereas rural areas consist of counties with populations under 50,000. Geographic regions were delineated into the Northeast, Midwest, South, and West, in accordance with the U.S. Census Bureau’s regional divisions.

To evaluate national mortality trends related to T2DM and malignant neoplasms of digestive organs, the age-adjusted mortality rate (AAMR) per 100,000 population was computed using the year 2000 US standard population as the reference. Temporal changes in mortality were examined with Joinpoint Regression Software (version 5.1.0; National Cancer Institute). Mortality rates were log-transformed, and log-linear models were applied to estimate the annual percent change (APC) along with its 95% confidence interval (CI). Trends were categorized as increasing or decreasing based on whether the APC significantly differed from zero, using a two-tailed t-test with exact P-values calculated for each trend segment. A significance threshold of P < 0.05 was applied across all demographic and geographic variables. Furthermore, a parallelism test (Permutation Test) was conducted to compare trends between subgroups (e.g., Male vs. Female, NH-Black vs. NH-White), with the resulting P-values used to determine if the divergence in average annual percent change (AAPC) was statistically significant. All statistical analyses were performed using Joinpoint (version 5.1.0, National Cancer Institute, USA) and R (version 4.2.2).

Results

Overall population

From 1999 to 2023, there were 94,676 deaths related to T2DM and malignant neoplasms of digestive organs in the United States. Overall AAMR increased during this period from 1.82 (95% CI:1.74–1.91) in 1999 to 4.93 (95% CI:4.82–5.04) in 2023, with an average annual percentage change (AAPC) of + 4.13% (95% CI: 3.83 to 4.56) (Table 1, Fig. 1, Supplementary Table 1). A sensitivity analysis, which restricted malignant neoplasms of digestive organs as the underlying cause of death while considering T2DM as a contributing factor, revealed the same trends: the AAMR exhibited a significant increase from 1999 to 2007 (APC: 4.70%; 95% CI: 2.8 to 11.75; p < 0.05), followed by a stable phase from 2007 to 2013 (APC: 0.31%; 95% CI: –5.21 to 6.69; p = 0.95). Subsequently, a significant increase occurred between 2013 and 2023 (APC: 7.07%; 95% CI: 5.91 to 8.60; p < 0.05) (Supplementary Figure S1).

Table 1.

Death and age-adjusted mortality rates per 100,000 in older adults with T2DM and malignant neoplasms of digestive organs concomitantly stratified in adults aged 45 years and older by gender, race, census region and urbanization

	Deaths	Population	AAMR 1999 (95% CI)	AAMR 2023 (95% CI)	AAPC (95% CI)
Overall	94,676	3,043,725,672	1.82 (1.74–1.91)	4.93(4.82–5.04)	4.13(3.83–4.56)
Gender
Male	56,290	1,427,661,266	2.4(2.24–2.55)	6.8(6.6–7.00)	4.39(4.01–4.99)
Female	38,386	1,616,064,406	1.43(1.33–1.53)	3.47(3.34–3.6)	3.91(3.42–5.00)
Race
Hispanic	11,078	308,938,513	1.91 (1.51–2.37)	6.71 (6.29–7.12)	5.56 (5.10–6.30)
NH White	68,340	2,245,334,172	1.75 (1.66–1.84)	4.64 (4.51–4.77)	4.00 (3.72–4.35)
NH Black or African American	9947	322,117,448	2.27 (1.94–2.61)	5.20 (4.82–5.57)	3.90 (3.36–4.85)
Census region of United States
Northeast	12,978	574,121,780	1.70 (1.51–1.88)	3.12 (2.91–3.33)	2.63 (2.16–3.30)
Midwest	23,495	668,417,547	2.45 (2.24–2.65)	4.87 (4.62–5.11)	3.29 (2.78–4.11)
South	30,305	1,127,663,361	1.50 (1.37–1.63)	4.61 (4.43–4.78)	4.71 (4.21–5.51)
West	27,898	673,522,984	1.72 (1.53–1.90)	7.08 (6.80–7.37)	6.58 (6.19–7.21)
Urbanization			AAMR 1999 (95% CI)	AAMR 2020 (95% CI)	AAPC (95% CI)
Large	32,572	1,393,581,246	1.47 (1.36–1.58)	3.90 (3.76–4.04)	4.71 (4.44–5.24)
Medium/small	23,585	794,661,897	1.97 (1.81–2.13)	4.78 (4.58–4.98)	3.95 (3.53–4.59)
Rural/counties	16,334	434,230,530	2.48 (2.25–2.71)	5.79 (5.48–6.09)	4.02 (3.43–4.85)

Fig. 1.

Trends in T2DM and malignant neoplasms of digestive organs related age adjusted mortality rates by Sex from 1999 to 2023. AAMR: Age-adjusted mortality rates; APC: Annual Percent Change

Sex-based differences

From 1999 to 2023, there were 56,290 deaths related to T2DM and malignant neoplasms of digestive organs in males, and 38,386 deaths in females. During this period, the AAMR in males increased fro m 2.4(95% CI:2.24–2.55) in 1999 to 6.8 (95% CI:6.6–7.00) in 2023, with an AAPC of + 4.39% (95% CI:4.01 to 4.99). The APC for males varied across time periods: 1999–2006: APC = + 4.97% (95% CI: 3.15 to 11.12); 2006–2014: APC = + 0.71% (95% CI: −3.95 to 2.20); 2014–2021: APC = + 9.14% (95% CI: 7.86 to 13.07); 2021–2023: APC = + 1.17% (95% CI: −2.85 to 6.17).

However, from 1999 to 2023, the AAMR in females increased from 1.43(95% CI:1.33–1.53) in 1999 to 3.47 (95% CI: 3.34–3.6) in 2023, with an AAPC of + 3.91 (3.42 to 5.00) (Table 1). The APC by time period for females was: 1999–2006: APC = + 4.25% (95% CI: + 1.55 to 14.49); 2006–2014: APC = −0.35% (95% CI: −8.33 to 8.23); 2014–2023: APC = + 7.59% (95% CI: 5.44 to 11.34) (Fig. 1, Table 1, Supplementary Table 1).

Race-based differences

From 1999 to 2023, there were 11,078 deaths related to T2DM and malignant neoplasms of digestive organs in Hispanic of the United States. During this period, the AAMR in Hispanic increased from 1.91 (95% CI: 1.51–2.37) in 1999 to 6.71 (95% CI:6.29–7.12) in 2023, with an AAPC of + 5.56% (95% CI:5.10 to 6.30) (Table 1, Fig. 2, Supplementary Table 2).

Fig. 2.

Trends in T2DM and malignant neoplasms of digestive organs related age adjusted mortality rates by Race from 1999 to 2023. AAMR: Age-adjusted mortality rates; APC: Annual Percent Change

From 1999 to 2023, there were 9,947 deaths related to T2DM and digestive organ malignancies in NH black or African American of the United States. During this period, the AAMR in NH black or African American increased from 2.27 (1.94–2.61) in 1999 to 5.20 (95% CI:4.82–5.57) in 2023, with an AAPC of + 3.90% (95% CI: 3.36 to 4.85). APC by time period for NH black or African American patients: 1999–2005: APC = + 7.66% (95% CI: 4.21 to 17.01); 2005–2013: APC = −1.20% (95% CI: −8.65 to 0.97);2013–2023: APC = + 5.89% (95% CI: 4.64 to 7.96) (Table 1, Fig. 2, Supplementary Table 2).

Among NH White, there were 68,340 deaths related to T2DM and digestive organ malignancies from 1999 to 2023. The AAMR of NH White increased from 1.75 (95% CI:1.66–1.84) in 1999 to 4.64 (95% CI: 4.51–4.77) in 2023. The AAPC was + 4.00% (95% CI: 3.72 to 4.35). APC by time period for NH White patients: 1999–2007: APC = + 4.40% (95% CI: 3.30 to 5.92); 2007–2014: APC = −1.24% (95% CI: −3.81 to −0.04); 2014–2021: APC = + 9.64% (95% CI: 8.80 to 12.14); 2021–2023: APC = + 2.05% (95% CI: −1.46 to 6.13) (Table 1, Fig. 2, Supplementary Table 2).

States-based differences

Significant geographical disparities in AAMRs were observed across the United States. Data from 2023 revealed substantial variations among states: South Carolina recorded an AAMR of 1.20 (95% CI: 0.82 to 1.70), whereas Oregon reported a markedly higher rate of 10.63 (95% CI: 9.22 to 12.05). The top 10% of states—including Minnesota, Wyoming, Kentucky, and California—exhibited AAMRs nearly ten times higher than those in the bottom 10% in 2023 (Fig. 3, Supplementary File).

Fig. 3.

State-wise distribution of T2DM and malignant neoplasms of digestive organs related age adjusted mortality rates from 1999 to 2023. AAMR: Age-adjusted mortality rates

Census region-based differences

In different states of the United States, the AAMR has also shown a gradually increasing trend over time (Table 1, Fig. 4, Supplementary Table 3). All census regions had an increase in AAMR over time, particularly in the West, which saw an increase in AAMR from 1.72 (95% CI: 1.53–1.90) in 1999 to 7.08 (95% CI: 6.80–7.37) in 2023, with an AAPC of + 6.58% (95% CI: 6.19 to 7.21).

Fig. 4.

Trends in T2DM and malignant neoplasms of digestive organs related age adjusted mortality rates by Census Region from 1999 to 2023. AAMR: Age-adjusted mortality rates; APC: Annual Percent Change

The Northeast APC by time period are as follows: 1999–2005: APC = + 3.90% (95% CI: 1.19 to 10.39);2005–2014: APC = −2.42% (95% CI: −8.15 to −1.00);2014–2023: APC = + 7.06% (95% CI: 5.67 to 8.93); In the South, APCs by time period were: 1999–2006: APC = + 4.46% (95% CI: 1.78 to 14.55); 2006–2014: APC = −0.20% (95% CI: −6.46 to 8.34); 2014–2023: APC = + 9.48% (95% CI: 7.91 to 11.33). Midwest APCs by time period: 1999–2006: APC = + 4.98% (95% CI: 2.39 to 11.99);2006–2014: APC = −2.07% (95% CI: −9.51 to 0.04);2014–2023: APC = + 6.94% (95% CI: 5.32 to 9.38) (Table 1, Fig. 4, Supplementary Table 3).

Urbanization-based differences

AAMRs were consistently higher in rural areas compared to small/medium, and large metropolitan regions throughout the study period. In rural zones, AAMR increased from 2.48 (95% CI: 2.25–2.71) in 1999 to 5.79 (95% CI: 5.48–6.09) in 2020, with an AAPC of + 4.02% (95% CI: 3.43 to 4.85) (Table 1, Fig. 5, Supplementary Table 4).

Fig. 5.

Trends in T2DM and malignant neoplasms of digestive organs related age adjusted mortality rates by Urbanization Level from 1999 to 2020. AAMR: Age-adjusted mortality rates; APC: Annual Percent Change

APC by time period for rural patients: 1999–2002: APC = + 11.30% (95% CI: 4.43 to 24.28); 2002–2014: APC = −0.43% (95% CI: −2.19 to 0.42); 2014–2020: APC = + 9.76% (95% CI: 7.60 to 12.85). In medium/small Metropolitan, AAMR increased from 1.97 (95% CI: 1.81–2.13) in 1999 to 4.78 (95% CI:4.58–4.98) in 2020, with an AAPC of + 3.95% (95% CI: 3.53 to 4.59) (Table 1, Fig. 5, Supplementary Table 4).

APC by time period for medium/small Metropolitan patients: 1999–2007: APC = + 4.57% (95% CI: 3.01 to 7.90);2007–2014: APC = −1.65% (95% CI: −6.77 to 0.19); 2014–2020: APC = + 10.02% (95% CI: 8.07 to 12.90). In large Metropolitan, AAMR increased from 1.47 (95% CI: 1.36–1.58) in 1999 to 3.90 (95% CI: 3.76–4.04) in 2020, with an AAPC of + 4.71% (95% CI: 4.44 to 5.24) (Table 1, Fig. 5, Supplementary Table 4).

APC by time period for large Metropolitan patients: 1999–2008: APC = + 5.08% (95% CI: 4.16 to 7.89); 2008–2012: APC = −0.33% (95% CI: −3.65 to 2.74);2012–2020: APC = + 6.92% (95% CI: 6.06 to 8.52) (Table 1, Fig. 5, Supplementary Table 4).

Age group stratified

Age groups were defined as 45–54, 55–64, 65–74, 75–84, and 85 + years of age. The population aged 85 + years had the highest overall crude mortality rate. The population aged 45–54 years had the lowest overall crude mortality rate.

APC by time period for patients aged 85 + years: 1999–2002: APC = + 8.03% (95% CI: 1.59 to 20.61); 2002–2015: APC = + 0.74% (95% CI: −2.85 to 5.16); 2015–2023: APC = + 7.78% (95% CI: 6.37 to 9.73); APC by time period for patients aged 75–84 years: 1999–2007: APC = + 4.84% (95% CI: 3.16 to 9.84); 2007–2013: APC = −1.00% (95% CI: −6.64 to 1.52); 2013–2023: APC = + 6.72% (95% CI: 5.72 to 8.21). APC by time period for patients aged 65–74 years: 1999–2005: APC = + 5.15% (95% CI: 2.47 to 16.40); 2005–2014: APC = + 0.43% (95% CI: −6.27 to 1.95); 2014–2020: APC = + 10.66% (95% CI: 8.56 to 16.70); 2020–2023: APC = + 2.32% (95% CI: −3.08 to 5.82); APC by time period for patients aged 55–64 years: 1999–2009: APC = + 4.98% (95% CI: 3.59 to 12.25); 2009–2014: APC = + 0.33% (95% CI: −5.08 to 4.76); 2014–2021: APC = + 10.01% (95% CI: 8.57 to 15.64); 2021–2023: APC = −0.04% (95% CI: −5.43 to 6.31). APC by time period for patients aged 45–54 years: 1999–2007: APC = + 9.96% (95% CI: 7.32 to 16.64); 2007–2012: APC = −2.28% (95% CI: −10.44 to 2.68); 2012–2023: APC = + 10.26% (95% CI: 8.95 to 12.39) (Fig. 6).

Fig. 6.

Trends in T2DM and malignant neoplasms of digestive organs related age adjusted mortality rates by Age from 1999 to 2023. CDR: Crude Death Rate; APC: Annual Percent Change

Discussion

The relationship between T2DM and digestive organ malignancies has become an important area of medical research in recent years. A large amount of epidemiological evidence indicates that the risk of developing liver, pancreas, colorectum, stomach, and biliary tract malignancies in T2DM patients is significantly higher than that in non-diabetic populations [12, 13]. This association may result from the interaction of multiple pathophysiological mechanisms, including hyperinsulinemia, activation of the insulin-like growth factor-1 (IGF-1) signaling pathway, chronic inflammatory state, hyperglycemic toxicity, and intestinal flora imbalance, etc. [14].

Multiple studies have shown that long-term T2DM is an independent risk factor for pancreatic cancer [4, 15]. A meta-analysis of multiple studies indicates that type 2 diabetes mellitus (T2DM) is closely associated with the risk of gastric cancer [16]. The relationship between colorectal cancer incidence and T2DM has also been confirmed in several studies [17]. A prospective study has demonstrated a high risk of liver malignancies in patients with T2DM [18]. These pieces of evidence all indicate that T2DM is associated with various malignant tumors of the digestive organs. However, there are currently no studies exploring the changes in mortality rates associated with T2DM and digestive organ malignancies.

This study aims to clarify the temporal trends of mortality related to type 2 diabetes mellitus (T2DM) and digestive organ malignancies in the United States from 1999 to 2023 by using the extensive Epide biological research online data database (CDC WONDER) of the US Centers for Disease Control and Prevention. At the same time, we attempt to identify the differences among gender, race, urbanization and geographical regions through this study, in order to provide targeted intervention measures, optimize clinical practices and formulate public health policies for this patient group. Our research indicates that from 1999 to 2023, the mortality rates associated with T2DM and digestive organ malignancies have been showing a gradually increasing trend. Males consistently have a higher AAMR than females. The observed upward trend in mortality may also be attributed to shifts in clinical practice and diagnostic frameworks over the past two decades. The transition to more stringent diagnostic criteria for T2DM—notably the standardized use of HbA1c since 2010—has led to increased detection of chronic metabolic dysfunction, potentially capturing a larger pool of high-risk individuals in mortality data [19]. Simultaneously, advancements in diagnostic imaging and the implementation of proactive screening protocols (such as expanded colonoscopy and high-resolution CT) have improved the detection of digestive malignancies. While these advancements facilitate earlier diagnosis, they also contribute to a higher recorded incidence and subsequent mortality linkage in national databases. Furthermore, changes in treatment modalities may play a dual role. While the widespread use of metformin has been associated with potential protective effects against certain cancers, the increasing reliance on exogenous insulin in advanced T2DM—which possesses mitogenic properties—and the rising complexity of managing multi-morbid elderly patients may contribute to the persistent elevation in mortality rates [20]. Sex differences in the prevalence and burden of these conditions may reflect variations in behavioral risk factors, including smoking, alcohol consumption, and specific dietary patterns (such as high intake of sugar, fats, and spicy foods), as reported in previous epidemiological studies. These behaviors are established risk factors not only for T2DM but also for malignant tumors of the digestive organs, potentially contributing to the observed gender disparity [21, 22]. Compared with urban areas, rural areas have also consistently had the highest AAMR. This is closely related to the level of economic development. Furthermore, rural–urban disparities observed in this study may reflect differences in healthcare access, socioeconomic factors, and preventive screening availability, as documented in prior studies. These systemic barriers often limit the early detection and effective management of chronic conditions in rural populations [23, 24]. The crude mortality rate for people aged 85 and above is higher than that of people in other age groups. The physical condition of the elderly is generally poor. Once they fall ill, they are more likely to suffer from severe complications and cannot receive effective treatment, thus increasing their risk of death [25].

There are also potential biological mechanisms that support the relationship between T2DM and malignant tumors of digestive organs. Firstly, patients with T2DM generally have insulin resistance, which leads to the compensatory excessive secretion of insulin by pancreatic β cells, resulting in hyperinsulinemia. Insulin can activate downstream RAS/MAPK and PI3K/Akt signaling pathways through certain receptors [26, 27]. These pathways are key regulators of cell proliferation, differentiation, and apoptosis, and their excessive activation can significantly inhibit cell apoptosis and promote cell cycle progression, thereby driving the occurrence and development of tumors [28]. Secondly, tumor cells mainly rely on the Warburg effect (rapid glycolysis even under aerobic conditions) to rapidly obtain energy. The high glucose environment provides sufficient substrates for tumor cells to meet their energy requirements for malignant proliferation [29, 30]. Moreover, T2DM is considered a chronic inflammatory disease. The chronic inflammatory environment can inhibit the functions of dendritic cells and T cells, disrupt normal immune surveillance, and make it difficult for the body to recognize and eliminate early cancer cells [31, 32].

Overall, T2DM is closely related to malignant tumors of the digestive organs. This study emphasizes the importance of conducting tumor screening and prevention for diabetic patients by describing the related deaths of T2DM and digestive organ malignancies. For instance, for long-term diabetic patients, enhanced monitoring such as colonoscopy and abdominal imaging is necessary. Meanwhile, blood sugar control (such as through lifestyle intervention or medication) may help reduce the risk of tumors. However, the potential association between certain hypoglycemic drugs (such as exogenous insulin) and the risk of tumors still requires further research to optimize treatment strategies [33, 34]. Moreover, highlighting healthy living habits for the prevention and control of the disease is the purpose of our current study.

Despite the significant findings, several limitations of this study must be acknowledged. First, the CDC WONDER database possesses inherent limitations, as it lacks granular clinical information such as specific tumor staging, histopathological subtypes, and detailed treatment modalities. The absence of these parameters may introduce residual confounding, as they are critical determinants of clinical outcomes for both T2DM and digestive malignancies. Second, potential misclassification errors in the recording of cause-of-death on death certificates might affect the precision of our mortality estimates, although the CDC implements rigorous quality control measures. Third, as this is a cross-sectional study, it can only identify associations and temporal trends rather than establish direct causal relationships. Fourth, the potential influence of the COVID-19 pandemic on mortality patterns between 2020 and 2022 cannot be ignored. The observed shifts during this period may be partially attributed to disruptions in routine healthcare services, delayed screenings for malignancies, and the increased physiological vulnerability of T2DM patients to viral infections. Finally, while the findings provide a comprehensive overview of the U.S. population, their generalizability to other regions or healthcare systems with different socioeconomic structures may be limited. However, despite these constraints, this study significantly enriches the existing literature by providing a detailed mapping of long-term mortality trends. Our findings emphasize the critical need for targeted public health interventions and policy optimizations tailored to the specific requirements of vulnerable demographic groups.

Conclusions

From 1999 to 2023, the United States experienced a significant escalation in mortality associated with the co-occurrence of T2DM and digestive organ malignancies. Our analysis identifies that this rising burden is concentrated within specific high-risk subgroups, notably males, Non-Hispanic Black populations, and residents of rural areas, likely driven by systemic disparities in healthcare access, lifestyle risk factors, and suboptimal cancer screening rates. These findings suggest that the synergy between diabetes and gastrointestinal carcinogenesis is intensified by socioeconomic inequities. Therefore, mitigating this trend requires targeted public health interventions, such as integrated metabolic-oncology screenings for high-burden racial minorities and expanded healthcare infrastructure in rural regions, to reduce preventable deaths and achieve health equity.

Authors’ contributions

Sidan Xu designed the study; Wei Xu wrote the manuscript.

Funding

This study was not supported by any funding.

Data availability

Data will be made available on https://wonder.cdc.gov/.

Declarations

Ethics approval and consent to participate

The analyses were based on publicly available data that had been approved by relevant review boards.

Competing interests

The authors declare no competing interests.