S90 New-Onset Diabetes Mellitus and the Risk of Pancreatic Adenocarcinoma: A Propensity Matched Population-Level Study Using Hemoglobin A1c
Bibliographic record
Abstract
Introduction: Seminal studies have linked diabetes mellitus (DM) with pancreatic adenocarcinoma (PDAC) mostly using fasting blood glucose levels. We sought to validate the risk of PDAC in patients with new-onset DM using hemoglobin A1c levels given the difficulty in ascertaining if glucose levels used in prior studies were truly fasting. Methods: We performed a retrospective cohort study using data from TriNetX, a multi-institutional database of over 79 million patients across 49 healthcare organizations. Patients ≥18 years old with a diagnosis of DM determined by the ICD-10 codes and hemoglobin A1c ≥6.5 from 2006-2022 were included in the analysis cohort. Patients with a history of pancreatic neuroendocrine tumors, pancreas surgery, and/or PDAC before a diagnosis of DM were excluded. We assessed PDAC risk within 2 years of new-onset DM compared to a non-DM cohort after 1:1 propensity score matching for age, gender, race, tobacco, alcohol, chronic pancreatitis, exocrine pancreatic insufficiency, BMI, and family history of GI or pancreatic malignancy. PDAC risk was expressed as adjusted odds ratios (aOR) with 95% confidence intervals. Results: Of 1,152,375 patients with DM, 0.42% (n=4,883) developed PDAC (mean age 67.5 +/- 10.8 years, 56% male, 70% White). The PDAC group was older (mean age 67.5 ± 10.8 vs 58.6 ± 14.0, P< 0.0001), and had higher A1c levels (8.37% ± 2.01 vs 8.23% ± 2.01, P< 0.001), but lower BMI (29 ± 6.44 vs 32.6 ± 7.09). After propensity score matching, using hemoglobin A1c levels, patients with new-onset DM had an increased risk of PDAC compared to the non-DM cohort (aOR 2.6, 95% CI 2.45-2.76, P< 0.0001). Furthermore, patients with PDAC diagnosed after DM onset were more likely to undergo pancreatic surgery compared to those without DM (aOR 1.54, 95% CI 1.32-1.80, P< 0.0001). However, there was no difference in all-cause mortality between the DM and non-DM cohorts (aOR 0.95, 95% CI 0.89-1.007, P= 0.15). Patients with older age, male sex, history of acute pancreatitis, chronic pancreatitis, nicotine dependence, and insulin therapy at diagnosis who develop new-onset DM were at an increased risk of PDAC (Table 1). Conclusion: New-onset DM diagnosed via hemoglobin A1c is associated with an increased risk of PDAC, especially in older male patients with a history of pancreatitis, nicotine dependence, and insulin therapy for DM. Hemoglobin A1c may be more reliable than fasting blood glucose for predictive models of PDAC risk in patients with diabetes. Table 1. - Risk of PDAC in Patients with New-Onset DM Based on Demographic Parameters and Co-Morbid Conditions Variables Adjusted odds ratio 95% confidence interval P value Age groups (compared to age ≥75) 18-39 0.05 0.03-0.07 < 0.0001 40-64 0.27 0.25-0.30 < 0.0001 65-74 0.67 0.62-0.72 < 0.0001 Male sex (compared to female sex) 1.13 1.06-1.20 < 0.0001 Race (compared to White) Blacks/African American 0.92 0.83-1.01 0.11 Hispanic or Latino 0.71 0.60-0.84 < 0.0001 Asian 0.88 0.69-1.12 0.3 American Indian or Alaska Native 0.78 0.44-1.37 0.39 Comorbidities, Yes vs No Acute pancreatitis 1.4 1.10-1.79 0.005 Chronic pancreatitis 3.92 2.77-5.55 < 0.0001 Alcohol-related disorders 0.77 0.58-1.02 0.07 Nicotine dependence 1.44 1.21-1.70 < 0.0001 Exocrine pancreatic insufficiency 0.95 0.41-2.22 0.92 Insulin therapy at diagnosis of DM 2.21 1.88-2.61 < 0.0001
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".