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Original Investigation
August 13, 2020

Diabetes, Weight Change, and Pancreatic Cancer Risk

Author Affiliations
  • 1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
  • 2Department of Internal Medicine, Baylor College of Medicine, Houston, Texas
  • 3Gastroenterology and Hepatology, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas
  • 4Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • 5Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
  • 6Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
  • 7Yale Cancer Center, Smilow Cancer Hospital, New Haven, Connecticut
  • 8Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
  • 9Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
  • 10Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • 11Department of Cell Biology, Harvard Medical School, Boston, Massachusetts
  • 12cBio Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
  • 13Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
JAMA Oncol. 2020;6(10):e202948. doi:10.1001/jamaoncol.2020.2948
Key Points

Question  Is there an association of diabetes duration and recent weight loss with subsequent risk of pancreatic cancer?

Findings  In this cohort study of 112 818 women and 46 207 men enrolled in 2 US cohort studies, participants with recent-onset diabetes accompanied by weight loss of 1 to 8 lb or more than 8 lb had a substantially increased risk for pancreatic cancer compared with participants with no such exposure.

Meaning  The findings from this study suggest that individuals with recent-onset diabetes accompanied by weight loss have a high risk for developing pancreatic cancer and may be a group for whom early detection strategies would be advantageous.

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.

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