Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct 1;6(10):e202948.
doi: 10.1001/jamaoncol.2020.2948. Epub 2020 Oct 8.

Diabetes, Weight Change, and Pancreatic Cancer Risk

Chen Yuan  1 , Ana Babic  1 , Natalia Khalaf  2   3 , Jonathan A Nowak  4   5 , Lauren K Brais  1 , Douglas A Rubinson  1 , Kimmie Ng  1 , Andrew J Aguirre  1 , Pari V Pandharipande  6 , Charles S Fuchs  7 , Edward L Giovannucci  8   9   10 , Meir J Stampfer  8   9   10 , Michael H Rosenthal  1 , Chris Sander  11   12 , Peter Kraft  8   13 , Brian M Wolpin  1
Affiliations

Diabetes, Weight Change, and Pancreatic Cancer Risk

Chen Yuan et al. JAMA Oncol. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Yuan reported receiving grants from the Helen Gurley Brown Presidential Initiative during the conduct of the study. Dr Ng reported receiving grants from the Broman Fund for Pancreatic Cancer Research and the Helen Gurley Brown Presidential Initiative during the conduct of the study. Dr Aguirre reported receiving grants from Lustgarten Foundation and National Cancer Institute (NCI) during the conduct of the study; personal fees from Merck, Oncorus, and Arrakis Therapeutics outside the submitted work; and research funding from Mirati Therapeutics and Deerfield Inc outside the submitted work. Dr Pandharipande reported receiving grants from Medical Imaging and Technology Alliance outside the submitted work. Dr Fuchs reported receiving personal fees from Agios, Amylin Pharmaceuticals, Bain Capital, CytomX Therapeutics, Daiichi-Sankyo, Eli Lilly, Entrinsic Health, EvolveImmune Therapeutics, Genentech, Merck, Taiho, and Unum Therapeutics outside the submitted work; serving as a director for CytomX Therapeutics; owning unexercised stock options for CytomX and Entrinsic Health; and being a cofounder of and having equity in EvolveImmune Therapeutics. Dr Stampfer reported receiving grants from Brigham and Women’s Hospital and Harvard School of Public Health during the conduct of the study. Dr Rosenthal reported receiving grants from National Institutes of Health (NIH), Stand Up To Cancer Foundation, and Lustgarten Foundation during the conduct of the study. Dr Kraft reported receiving grants from NIH during the conduct of the study. Dr Wolpin reported receiving grants from NIH/NCI, Lustgarten Foundation, Eli Lilly, and Stand Up to Cancer during the conduct of the study; grants and personal fees from Celgene; and personal fees from BioLineRx and GRAIL outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Pancreatic Cancer Incidence by Combined Status of Diabetes and Recent Weight Change
Incidence rates are presented as cases per 100 000 person-years for participants in 4 groups of exposure: no diabetes and no weight loss, no diabetes and weight loss greater than 8 lb (to convert weight to kg, multiply by 0.45), recent-onset diabetes (≤4 years) and no weight loss, and recent-onset diabetes (≤4 years) and weight loss greater than 8 lb. Incidence rates were calculated by dividing the number of cases by the number of person-years in each group of exposure, with 95% CIs estimated by a Poisson distribution (only lower limits are shown). BMI indicates body mass index (calculated as weight in kilograms divided by height in meters squared).
Figure 2.
Figure 2.. Twenty-Year Trend in Body Mass Index (BMI) Before Diagnosis in Patients With Pancreatic Cancer and in Control Participants Without Pancreatic Cancer
Each incident case was matched to 5 control participants who were free of pancreatic cancer at the time of the case diagnosis, based on age (within 12 months), sex/cohort, race/ethnicity (White, Black, other, or unknown), and diabetes duration (no diabetes, ≤4 years, or >4 years).
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30. doi:10.3322/caac.21590 - DOI - PubMed
    1. Canto MI, Almario JA, Schulick RD, et al. . Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance. Gastroenterology. 2018;155(3):740-751.e2. doi:10.1053/j.gastro.2018.05.035 - DOI - PMC - PubMed
    1. Vasen H, Ibrahim I, Ponce CG, et al. . Benefit of surveillance for pancreatic cancer in high-risk individuals: outcome of long-term prospective follow-up studies from three European expert centers. J Clin Oncol. 2016;34(17):2010-2019. doi:10.1200/JCO.2015.64.0730 - DOI - PubMed
    1. Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreatic cancer. Lancet. 2016;388(10039):73-85. doi:10.1016/S0140-6736(16)00141-0 - DOI - PubMed
    1. Owens DK, Davidson KW, Krist AH, et al. ; US Preventive Services Task Force . Screening for pancreatic cancer: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2019;322(5):438-444. doi:10.1001/jama.2019.10232 - DOI - PubMed