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Diabetes, Weight Change, and Pancreatic Cancer Risk
Open accessAbstract
Importance: Pancreatic cancer is the third-leading cause of cancer death in the United States; however, few high-risk groups have been identified to facilitate early diagnosis strategies. Objective: To evaluate the association of diabetes duration and recent weight change with subsequent risk of pancreatic cancer in the general population. Design, Setting, and Participants: This cohort study obtained data from female participants in the Nurses' Health Study and male participants in the Health Professionals Follow-Up Study, with repeated exposure assessments over 30 years. Incident cases of pancreatic cancer were identified from self-report or during follow-up of participant deaths. Deaths were ascertained through reports from the next of kin, the US Postal Service, or the National Death Index. Data collection was conducted from October 1, 2018, to December 31, 2018. Data analysis was performed from January 1, 2019, to June 30, 2019. Exposures: Duration of physician-diagnosed diabetes and recent weight change. Main Outcome and Measures: Hazard ratios (HRs) for subsequent development of pancreatic cancer. Results: Of the 112 818 women (with a mean [SD] age of 59.4 [11.7] years) and 46 207 men (with a mean [SD] age of 64.7 [10.8] years) included in the analysis, 1116 incident cases of pancreatic cancers were identified. Compared with participants with no diabetes, those with recent-onset diabetes had an age-adjusted HR for pancreatic cancer of 2.97 (95% CI, 2.31-3.82) and those with long-standing diabetes had an age-adjusted HR of 2.16 (95% CI, 1.78-2.60). Compared with those with no weight loss, participants who reported a 1- to 4-lb weight loss had an age-adjusted HR for pancreatic cancer of 1.25 (95% CI, 1.03-1.52), those with a 5- to 8-lb weight loss had an age-adjusted HR of 1.33 (95% CI, 1.06-1.66), and those with more than an 8-lb weight loss had an age-adjusted HR of 1.92 (95% CI, 1.58-2.32). Participants with recent-onset diabetes accompanied by weight loss of 1 to 8 lb (91 incident cases per 100 000 person-years [95% CI, 55-151]; HR, 3.61 [95% CI, 2.14-6.10]) or more than 8 lb (164 incident cases per 100 000 person-years [95% CI, 114-238]; HR, 6.75 [95% CI, 4.55-10.00]) had a substantially increased risk for pancreatic cancer compared with those with neither exposure (16 incident cases per 100 000 person-years; 95% CI, 14-17). Incidence rates were even higher among participants with recent-onset diabetes and weight loss with a body mass index of less than 25 before weight loss (400 incident cases per 100 000 person-years) or whose weight loss was not intentional judging from increased physical activity or healthier dietary choices (334 incident cases per 100 000 person-years). Conclusions and Relevance: This study demonstrates that recent-onset diabetes accompanied by weight loss is associated with a substantially increased risk for developing pancreatic cancer. Older age, previous healthy weight, and no intentional weight loss further elevate this risk.
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“One such cohort is subjects with new-onset diabetes and a high score (≥3) on the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) model.4”
From Radiomics-based Machine-learning Models Can Detect Pancreatic Cancer on Prediagnostic Computed Tomography Scans at a Substantial Lead Time Before Clinical Diagnosis (2022) · cites this paper as [4]
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“Early detection offers survival benefit beyond lead time, as tumors are smaller in volume and more likely to be resectable when detected earlier.2-4”
From Radiomics-based Machine-learning Models Can Detect Pancreatic Cancer on Prediagnostic Computed Tomography Scans at a Substantial Lead Time Before Clinical Diagnosis (2022) · cites this paper as [4]
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“Although this association ’ s directionality and mechanisms are incompletely understood [4, 5], people with new-onset diabetes represent an important opportunity for identifying high-risk sub-populations suitable for further testing — new-onset ‘ T2DM ’ may in fact in some cases be type 3c…”
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Proteomics in pancreatic cancer
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Machine Learning Predicts Patients With New-onset Diabetes at Risk of Pancreatic Cancer
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“31,32 Such a feature is vital to END-PAC and Boursi ’ s models.”
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“Cumulative risk effects for developing PC may arise from diabetes accompanied by weight loss (40).”
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“…race, diabetes, family history of PC, genetic factors, chronic infection, non-O blood type, and chronic pancreatitis are main risk factors in PC [2]. extremely poor prognosis in PC is primarily due to the early onset of metastasis, and therefore, surgical resection is thought to be the mainstay…”
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“Notably, new-onset diabetes in older adults significantly increases PDAC risk, with a 7–8-fold rise, and up to 80% of patients exhibit hyper-glycemia or diabetes at diagnosis [101–103].”
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Prävention des Pankreaskarzinoms
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“BMI: Body-Mass-Index (angegeben in kg/m2) (nach Daten aus [27]).”
Weight loss during neoadjuvant therapy for pancreatic cancer does not predict poor outcomes
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Self-citationWeight Tracking as a Novel Prognostic Marker After Pancreatectomy
Hue, J. J., Ocuin, L. M., Kyasaram, R. K., Shanahan, J., Rao, G., Rothermel, L. D., Ammori, J. B., Hardacre, J. M., Winter, J. M., & Markt, S. C. (2022) · Annals of Surgical Oncology · doi:10.1245/s10434-022-11325-6 · Cited by 7
“This finding is similar to past reports on weight loss preceding a patient’s initial PDAC diagnosis, including a study by our group.(20,25) This insight may potentially improve time to diagnosis of recurrence.”
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“Although DM was not a significant factor in the prediction model for malignancy, we should remind that it is associated with a substantially increased risk of developing PDAC [23].”
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Li, L., Yu, X.-J., Gao, L., Cheng, L., Sun, B., & Wang, G. (2022) · Antioxidants and Redox Signaling · doi:10.1089/ars.2022.0101 · Cited by 7
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“25,32 As an example, Nicholson et al identified men over 50 years old and people who smoked (currently or in the past) to be the populations at highest risk of cancer with PPVs over the required threshold for investigation of 3%.”
Current paradigm and futuristic vision on new-onset diabetes and pancreatic cancer research
Moreland, R., Arredondo, A., Dhasmana, A., Dhasmana, S., Shabir, S., Siddiqua, A., Banerjee, B., Yallapu, M. M., Behrman, S. W., Chauhan, S. C., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1543112 · Cited by 6
Nishikawa, M., Yamamoto, J., Einama, T., Hoshikawa, M., Iwasaki, T., Nakazawa, A., Takihara, Y., Tsunenari, T., & Kishi, Y. (2022) · Pancreas · doi:10.1097/mpa.0000000000002186 · Cited by 6
The Influence of Metabolic Syndrome on the Development of Gastrointestinal Malignant Tumors—A Review
Brzački, V., Rančić, A., Tešić-Rajković, S., Nagorni, I., Stamenković, M., Stanković, E., Milutinović, N., & Vukadinović, A. (2025) · Medicina · doi:10.3390/medicina61061025 · Cited by 6
Typ-2-Diabetes-mellitus und Krebsrisiko
Scherübl, H. (2021) · DMW - Deutsche Medizinische Wochenschrift · doi:10.1055/a-1529-4521 · Cited by 6
“5-Fache, im Falle eines zusätzlichen Gewichtsverlustes sogar auf das 10–25-Fache an [20] (▶ Abb.”
BackgroundRajagopalan, A., Aroori, S., Russell, T. B., Labib, P. L. Z., Ausania, F., Pando, E., Roberts, K. J., Kausar, A., Mavroeidis, V. K., Marangoni, G., et al. (2024) · HPB · doi:10.1016/j.hpb.2024.04.010 · Cited by 10
He, R., Shen, Z., Chen, Q., Hu, H., Ding, X., Zheng, Z., Feng, Q., & Li, B. (2025) · BMC Cancer · doi:10.1186/s12885-025-13863-0 · Cited by 5
Liao, C.-Y., Schapiro, D., Mojdami, D., Sheffield, K. M., Hoog, M. M., Keni, R., Gathirua‐Mwangi, W. G., & Kan, H. J. (2025) · Endocrinology Diabetes & Metabolism · doi:10.1002/edm2.70104 · Cited by 5
Prediction of Pancreatic Cancer Risk in Patients with New-Onset Diabetes
Khan, S. (2025) · Visceral Medicine · doi:10.1159/000543479 · Cited by 5
“Long-standing diabetes doubles the risk of pancreatic cancer, new-onset diabetes triples the risk relative to the general population, and diabetes diagnosed within 1 year increases the risk sevenfold [10, 11].”
Rassy, E., Delaloge, S., Slaouti, Y., Pudlarz, T., Lekens, B., Boilève, A., Michiels, S., & Karimi, M. (2025) · British Journal of Cancer · doi:10.1038/s41416-025-03172-5 · Cited by 5
“The independent association between dyslipidemia and PDAC adds to the growing body of literature linking metabolic disorders and PDAC [19].”
Severe insulin resistance in a patient with diabetes after treatment with brentuximab vedotin
Peeters, G., & Verhaegen, A. A. (2024) · BMJ Case Reports · doi:10.1136/bcr-2022-251867 · Cited by 5
The critical need for guidance in managing glycaemic control in patients with cancer
Giovannucci, E. L. (2021) · Diabetic Medicine · doi:10.1111/dme.14624 · Cited by 5
Self-citationTime to Neoadjuvant Chemotherapy Initiation Is not Associated With Survival in Pancreatic Cancer
Hue, J. J., Sugumar, K., Elshami, M., Rothermel, L. D., Ammori, J. B., Hardacre, J. M., Winter, J. M., & Ocuin, L. M. (2022) · Journal of Surgical Research · doi:10.1016/j.jss.2022.03.013 · Cited by 5
Wang, X., Wang, H., Zhang, M., Li, H., Liu, Y., Huang, H., Pei, J., Huang, J., Zang, F., Zhang, Y., et al. (2025) · Cancer Discovery · doi:10.1158/2159-8290.cd-25-0323 · Cited by 4
Xiao, X., Yi, X., Soe, N. N., Latt, P. M., Lin, L., Chen, X., Song, H., Sun, B., Zhao, H., & Xu, X. (2024) · Annals of Epidemiology · doi:10.1016/j.annepidem.2024.12.003 · Cited by 4
Current Approaches of Pancreatic Cancer Surveillance in High-Risk Individuals
Heller, M., Mann, D. A., & Katona, B. W. (2025) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-025-01184-1 · Cited by 5
“Diabetes For individuals with long-standing type 2 diabetes mellitus (DM), the risk for PC is roughly 2-fold higher than the general population [43–45].”
Typ-2-Diabetes mellitus und gastrointestinale Krebsvorsorge
Scherübl, H. (2022) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1821-9108 · Cited by 5
“5-fache, im Falle eines zusätzlichen Gewichtsverlustes sogar auf das 10bis 25-fache an [43] (▶ Abb.”
Cai, J., Chen, H., Lu, M., Zhang, Y., Lu, B., Luo, C., Feng, X., You, L., Dai, M., & Zhao, Y. (2022) · Cancers · doi:10.3390/cancers14143403 · Cited by 4
“Much attention has been paid to the risks of PC in patients with diabetes in many studies [20,21], and our research suggests that glycemic changes in people without diabetes, both increases and decreases in FBG, are also worth monitoring to identify PC risk.”
BackgroundAfghani, E., Lau, B. M., Becker, L. K., Goggins, M., & Klein, A. P. (2025) · BMJ Open · doi:10.1136/bmjopen-2025-099488 · Cited by 4
“31 Based on our study, the younger individuals with a new diabetes diagnosis had a higher HR compared with older individuals.”
Verhoeff, K. K., & Shapiro, A. M. J. (2025) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2025.101414 · Cited by 3
Pancreatic Cancer and Diabetes: Insights, Hypotheses, and Next Steps
Hill, J. L. E., Hill, T. G., Parslow, D., & Hill, D. J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262110245 · Cited by 4
Clinical and Imaging Predictors of Pancreatic Cancer in Patients Hospitalized for Acute Pancreatitis
Luong, T. Q., Chen, Q., Tran, T. M., Zhou, Y., Lustigova, E., Chen, W., & Wu, B. U. (2022) · Gastro Hep Advances · doi:10.1016/j.gastha.2022.07.009 · Cited by 3
“18 Although weight loss coupled with new-onset diabetes in patients older than 50 years has been linked to increased short-term risk of pancreatic cancer in previous studies, 19,20 we did not identify such an association with recent-onset diabetes among patients with AP.”
BackgroundSun, Y., Wan, H., Xiong, J., Cao, K., Yang, D., & Huang, J. X. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1559909 · Cited by 3
“The strong association between chronic subclinical in fl ammation triggered by metabolic syndrome and pancreatic cancer has been widely acknowledged (28).”
Tao, L. V., Karasinska, J. M., Souza, V. G. P., Loree, J. M., Johnson, J. D., Renouf, D. J., & Schaeffer, D. F. (2026) · Frontiers in Gastroenterology · doi:10.3389/fgstr.2025.1645459 · Cited by 3
“…loss at PDAC diagnosis compared to weight prior to diabetes onset had a higher adjusted odds ratio in PDAC-associated diabetes individuals compared to T2D (93), while age-adjusted hazard risk for PDAC-associated diabetes increased with increasing weight loss in NOD individuals compared to T2D (26).”
Yang, J., Cao, B., Yuemaierabola, A., Gong, Y., Guo, Y., Zhong, H., Zhang, K., Wang, S., Huang, Q., Li, J., et al. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-07767-1 · Cited by 3
“Among individuals with NODM, the 3-year cumulative incidence of PC after NODM was 0.51%, corresponding to a 4.6-fold higher risk based on the standardized incidence ratio [17, 18].”
InfluentialBogdanski, A. M., Onnekink, A. M., Inderson, A., Boekestijn, B., Bonsing, B. A., Vasen, H. F. A., van Hooft, J. E., Boonstra, J. J., Mieog, J. S. D., Wasser, M. N. J. M., et al. (2024) · Pancreas · doi:10.1097/mpa.0000000000002335 · Cited by 2
Shan, Y., Teng, Y., Guan, C., Zhenbiao, M., Lu, C., Ding, W., & Zhang, J. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e34028 · Cited by 2
“In addition to realizing early diagnosis based on clinical examination or biomarkers, it is very important to identify relevant risk factors and populations for those who are at high risk of PC [20,21].”
BackgroundYang, M., Luo, J., Zheng, Y., & Chen, Q. (2025) · International Journal of Endocrinology · doi:10.1155/ije/7734237 · Cited by 2
“Type 2 diabetes mellitus (T2DM) is recognized globally as a chronic ailment [3].”
The Diabetes-Pancreatic Cancer Risk Relationship over Time: A Systematic Review and Meta-Analysis
Fuentes, A., Montserrat-Capdevila, J., Florensa, D., Godoy, S., Serrano, J., & Godoy, P. (2025) · Diabetology · doi:10.3390/diabetology6110131 · Cited by 2
Diabetogenic liver metastasis from pancreatic cancer: a case report
Kiritani, S., Ono, Y., Takamatsu, M., Oba, A., Sato, T., Ito, H., Inoue, Y., & Takahashi, Y. (2022) · Surgical Case Reports · doi:10.1186/s40792-022-01582-8 · Cited by 2
The Role of Diabetes Mellitus in the Malignant Pancreatic Cyst Neoplasm Diagnosis and Prognosis
Deng, J., Guo, Y., Gu, J., Du, J., Kong, L., Tao, B., Li, J., & Fu, D. (2022) · Cancer Management and Research · doi:10.2147/cmar.s355365 · Cited by 2
“According to the data from previous studies, the definition of new-onset diabetes mellitus (NODM) is DM diagnosed within four years from PCN diagnosis.(17,18) DM patients who had DM for more than four years were taken into the long-standing diabetes mellitus (LSDM) group.”
MethodBasaldúa-Maciel, V., Martínez–Esquivias, F., & Guzmán‐Flores, J. M. (2025) · Current Medicinal Chemistry · doi:10.2174/0109298673352470250312082922 · Cited by 1
Zhao, L., Tu, J., Zuo, H., Yin, F., Gao, T., Lu, M., Xie, L., & Zhang, C. (2025) · Gut Medicine · doi:10.1002/gtm2.70001 · Cited by 1
Post-surgery weight changes in pancreatic cancer: a prospective study on factors and survival impact
Cui, L., Zhang, L., Yu, H., Sun, Q., Jiang, K., Wei, J., & Fang, X. (2026) · World Journal of Surgical Oncology · doi:10.1186/s12957-026-04202-z · Cited by 1
“Additionally, weight was primarily self-reported, which may introduce differential measurement error—especially if severely affected patients under-report—a common concern in observational studies [37].”
Martínez-Gutiérrez, J., Somasundaram, K., Bernardes, C. M., Rafiq, M., Schrader, S., Jordan, S. J., Chima, S., Mendonca, L. D., Huckvale, K., Hunter, B., et al. (2026) · JMIR Formative Research · doi:10.2196/79209 · Cited by 1
Advancing precision medicine in pancreatic cancer using novel biomarkers and clinical targets
Murthy, D., Seyhan, A. A., den Hollander, P., Lu, S., Kuburich, N. A., Gould, C., Karam, A., Sun, K., Schupp, P. G., Safran, H., et al. (2026) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2026.101476 · Cited by 2
Huang, K., Huang, Z., He, Y., Zhao, P., & Hu, X. (2026) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.70205 · Cited by 1
Li, M., Gu, A., Li, J.-T., Tang, N.-N., Matin, M., Zhang, G., & Atanasov, A. G. (2026) · Food & medicine homology. · doi:10.26599/fmh.2027.9420153 · Cited by 1
Unintentional Weight Loss as a Marker of Malignancy Across Body Weight Categories
Hue, J. J., Ufholz, K. E., Winter, J. M., & Markt, S. C. (2021) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-021-00674-8 · Cited by 2
Krebsrisiko bei Prädiabetes und Typ-2-Diabetes mellitus
Scherübl, H. (2022) · Diabetologie und Stoffwechsel · doi:10.1055/a-1837-2035 · Cited by 1
Metadata
- Authors
- Yuan, C., Babic, A., Khalaf, N., Nowak, J. A., Brais, L. K., Rubinson, D. A., Ng, K., Aguirre, A. J., Pandharipande, P. V., Fuchs, C. S., Giovannucci, E. L., Stampfer, M. J., Rosenthal, M. H., Sander, C., Kraft, P., & Wolpin, B. M.
- Affiliations
- Harvard University (US)
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
- Michael E. DeBakey VA Medical Center (US)
- Brigham and Women's Hospital (US)
- Yale Cancer Center (US)
- Corresponding author
- Yuan, Chen
- ORCID
- Venue
- JAMA Oncology
- Publisher
- American Medical Association (AMA)
- Published
- 2020-10-08
- Volume
- 6
- Issue
- 10
- Pages
- e202948
- ISSN
- 2374-2437 (ISSN-L)
- PMC
- PMC7426876
- OpenAlex
- W3048739465
- Cited by
- 150
- References
- 40
- Citations by year
- 2026: 28 · 2025: 31 · 2024: 17 · 2023: 24 · 2022: 28 · 2021: 22
- FWCI
- 6.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (K08CA218420, R01CA205406)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- pancreatic cancer risk, diabetes duration, weight loss, recent-onset diabetes, long-standing diabetes, diabetes and cancer association, cancer risk factors, prospective cohort, Nurses' Health Study, Health Professionals Follow-up Study, early cancer detection, obesity and cancer risk, cancer screening guidelines, cancer survivorship, cancer survivorship support services, survivorship care
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms, Cohort Studies, Weight Loss, Body Mass Index, Incidence, Diabetes Complications
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