Early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed before age 50, has been increasing in many regions worldwide. Women of childbearing age (WCBA, 15–49 years) substantially overlap with the EOPC population and have distinct metabolic vulnerabilities related to reproductive-age physiology. Metabolic dysregulation—particularly hyperglycemia and obesity—are established contributors to pancreatic carcinogenesis through mechanisms such as insulin/IGF signaling and inflammation mediated by adipose-derived cytokines. Given rising global prevalence of diabetes and obesity, the authors frame EOPC burden specifically within WCBA to highlight reproductive-age metabolic risks and inform targeted prevention.
The study used a two-stage design. First, the authors analyzed publicly available Global Burden of Disease (GBD) 2023 estimates to assess EOPC deaths and disability-adjusted life years (DALYs) among women aged 15–49 from 1990 to 2023. Pancreatic cancer was defined by ICD-10 code C25 and EOPC as diagnosis before age 50. Key metrics included absolute counts and age-standardized rates (ASRs) per 100,000 with 95% uncertainty intervals. Countries and regions were stratified using the Sociodemographic Index (SDI), categorized as high, high-middle, middle, low-middle, and low.
Temporal trends were quantified with estimated annual percentage change (EAPC) from log-linear regression and joinpoint regression to identify inflection points. A demographic-epidemiological decomposition method partitioned changes in absolute burden into contributions from population growth, population aging, and epidemiological change. Population-attributable fractions (PAFs) for high fasting blood glucose (FBG) and high BMI were estimated using standard GBD comparative risk assessment methods.
Second, a retrospective case-control study was conducted to provide clinical correlation for the GBD-identified metabolic risk factors. The clinical analysis was explicitly described as supportive and hypothesis-generating rather than definitive. De-identified clinical data underlying the case-control analysis are provided as supporting information in the manuscript.
Between 1990 and 2023, the absolute number of EOPC deaths and DALYs among WCBA more than doubled globally. The rise in absolute burden was largely attributed to demographic forces—population growth and population aging—rather than uniform increases in age-standardized rates at the global level. The manuscript reports that demographic factors accounted for the majority of the absolute increase.
Despite the increase in absolute numbers, global age-standardized mortality and DALY rates for EOPC among WCBA remained broadly stable across the study period. However, stratification by SDI revealed heterogeneity: age-standardized rates increased in low and middle SDI regions, indicating disproportionate epidemiological shifts in those settings. High SDI regions did not show comparable rises in ASRs.
The GBD-derived comparative risk assessment identified high fasting blood glucose (FBG) as the largest population-attributable risk factor for EOPC in WCBA, with a global PAF reported at approximately 64%. The PAF for high FBG displayed an inverse SDI gradient, meaning its relative contribution was greater in lower SDI settings. The PAF for high BMI followed an inverted U-shaped distribution across SDI categories. These patterns suggest complex interactions between socio-demographic context and metabolic risk exposures.
In the supporting retrospective case-control study, elevated fasting blood glucose remained independently associated with EOPC after multivariable adjustment (adjusted odds ratio 4.64; 95% CI: 2.88–7.49). High BMI did not remain statistically significant after adjustment, suggesting that hyperglycemia may dominate in the observed metabolic risk signal or that BMI and hyperglycemia share overlapping causal pathways. The authors note that reverse causation could partly account for strong hyperglycemia associations in EOPC and caution that the clinical data are hypothesis-generating.
The study synthesizes population-level GBD evidence with clinical case-control data to argue that the growing absolute burden of EOPC in WCBA is principally driven by demographic change, while metabolic risks—especially elevated fasting glucose—contribute substantially to population-level attributable risk. Geographic and socio-demographic heterogeneity was evident: age-standardized rates rose in low and middle SDI regions and high FBG PAFs were higher in lower SDI strata. The loss of independent significance for BMI in adjusted clinical models suggests interplay between obesity and hyperglycemia rather than distinct independent effects in the examined dataset.
The authors emphasize interpretive caveats: GBD comparative risk estimates depend on exposure and outcome modeling assumptions, and the retrospective clinical analysis is not confirmatory. They also highlight the possibility of reverse causation—where preclinical pancreatic cancer perturbs glucose metabolism—contributing to observed associations.
Absolute EOPC deaths and DALYs among WCBA have increased substantially since 1990, mainly due to population growth and aging. High fasting blood glucose emerges as the leading modifiable population-level risk factor in WCBA, with implications for targeted metabolic and glycemic interventions. The authors call for prioritized prevention and metabolic health management in WCBA—especially in low and middle SDI regions—and for further research to disentangle causality from reverse causation.
The study used publicly available GBD 2023 data from the Institute for Health Metrics and Evaluation. De-identified clinical supporting data are provided as supporting information (S2 Data). Funding sources were disclosed (several projects supported by Bishan Hospital of Chongqing Medical University), and the authors declared no competing interests. The manuscript notes that funders did not influence study design, data collection, analysis, or publication decisions.