Diabetes Mellitus and Obesity As Risk Factors for Pancreatic Cancer

Overview

Journal J Acad Nutr Diet

Publisher Elsevier

Specialty Nutritional Sciences

Date 2017 Sep 19

PMID 28919082

Citations 65

Authors

Guido Eibl

Zobeida Cruz-Monserrate

Murray Korc

Maxim S Petrov

Mark O Goodarzi

William E Fisher

Aida Habtezion

Aurelia Lugea

Stephen J Pandol

Phil A Hart

Dana K Andersen

Affiliations

Soon will be listed here.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer. The worldwide estimates of its incidence and mortality in the general population are eight cases per 100,000 person-years and seven deaths per 100,000 person-years, and they are significantly higher in the United States than in the rest of the world. The incidence of this disease in the United States is more than 50,000 new cases in 2017. Indeed, total deaths due to PDAC are projected to increase dramatically to become the second leading cause of cancer-related deaths before 2030. Considering the failure to date to efficiently treat existing PDAC, increased effort should be undertaken to prevent this disease. A better understanding of the risk factors leading to PDAC development is of utmost importance to identify and formulate preventive strategies. Large epidemiologic and cohort studies have identified risk factors for the development of PDAC, including obesity and type 2 diabetes mellitus. This review highlights the current knowledge of obesity and type 2 diabetes as risk factors for PDAC development and progression, their interplay and underlying mechanisms, and the relation to diet. Research gaps and opportunities to address this deadly disease are also outlined.

Citing Articles

Screening of common genomic biomarkers to explore common drugs for the treatment of pancreatic and kidney cancers with type-2 diabetes through bioinformatics analysis.

Ajadee A, Mahmud S, Sarkar A, Noor T, Ahmmed R, Haque Mollah M Sci Rep. 2025; 15(1):7363.

PMID: 40025145 PMC: 11873208. DOI: 10.1038/s41598-025-91875-3.

Informatics strategies for early detection and risk mitigation in pancreatic cancer patients.

Jin D, Khan N, Gu W, Lei H, Goel A, Chen T Neoplasia. 2025; 60:101129.

PMID: 39842383 PMC: 11763847. DOI: 10.1016/j.neo.2025.101129.

Select Endocrine Disorders and Exosomes in Early PDAC Diagnosis.

Wlodarczyk B, Durko L, Walczak K, Talar-Wojnarowska R, Malecka-Wojciesko E Int J Mol Sci. 2024; 25(22).

PMID: 39596226 PMC: 11594802. DOI: 10.3390/ijms252212159.

Mapping Obesity Trends in Saudi Arabia: A Four-Year Description Study.

Althumiri N, Bindhim N, Al-Rayes S, Alumran A Healthcare (Basel). 2024; 12(20).

PMID: 39451507 PMC: 11507986. DOI: 10.3390/healthcare12202092.

Platelet-Derived Growth Factor C Facilitates Malignant Behavior of Pancreatic Ductal Adenocarcinoma by Regulating SREBP1 Mediated Lipid Metabolism.

Shi Y, Liu Z, Ma M, Zhao G, Zhu Y, Wang J Adv Sci (Weinh). 2024; 11(40):e2407069.

PMID: 39225567 PMC: 11516052. DOI: 10.1002/advs.202407069.

References

Conroy M, Dunne M, Donohoe C, Reynolds J . Obesity-associated cancer: an immunological perspective. Proc Nutr Soc. 2015; 75(2):125-38. DOI: 10.1017/S0029665115004176. View

Simopoulos A . An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity. Nutrients. 2016; 8(3):128. PMC: 4808858. DOI: 10.3390/nu8030128. View

Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L . A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2016; 23(1):107-113. DOI: 10.1038/nm.4236. View

Ulven T, Christiansen E . Dietary Fatty Acids and Their Potential for Controlling Metabolic Diseases Through Activation of FFA4/GPR120. Annu Rev Nutr. 2015; 35:239-63. DOI: 10.1146/annurev-nutr-071714-034410. View

Hursting S . Obesity, energy balance, and cancer: a mechanistic perspective. Cancer Treat Res. 2013; 159:21-33. DOI: 10.1007/978-3-642-38007-5_2. View

Sah R, Nagpal S, Mukhopadhyay D, Chari S . New insights into pancreatic cancer-induced paraneoplastic diabetes. Nat Rev Gastroenterol Hepatol. 2013; 10(7):423-33. PMC: 3932322. DOI: 10.1038/nrgastro.2013.49. View

Tschop M, Heiman M . Rodent obesity models: an overview. Exp Clin Endocrinol Diabetes. 2001; 109(6):307-19. DOI: 10.1055/s-2001-17297. View

Johansen D, Stocks T, Jonsson H, Lindkvist B, Bjorge T, Concin H . Metabolic factors and the risk of pancreatic cancer: a prospective analysis of almost 580,000 men and women in the Metabolic Syndrome and Cancer Project. Cancer Epidemiol Biomarkers Prev. 2010; 19(9):2307-17. DOI: 10.1158/1055-9965.EPI-10-0234. View

He K, Xun P, Brasky T, Gammon M, Stevens J, White E . Types of fish consumed and fish preparation methods in relation to pancreatic cancer incidence: the VITAL Cohort Study. Am J Epidemiol. 2012; 177(2):152-60. PMC: 3590032. DOI: 10.1093/aje/kws232. View

10.

Kim J, Chung K, Choi C, Beloor J, Ullah I, Kim N . Silencing CCR2 in Macrophages Alleviates Adipose Tissue Inflammation and the Associated Metabolic Syndrome in Dietary Obese Mice. Mol Ther Nucleic Acids. 2016; 5:e280. PMC: 5012549. DOI: 10.1038/mtna.2015.51. View

11.

Wu W, Wang C . Association between non-alcoholic fatty pancreatic disease (NAFPD) and the metabolic syndrome: case-control retrospective study. Cardiovasc Diabetol. 2013; 12:77. PMC: 3682938. DOI: 10.1186/1475-2840-12-77. View

12.

Pavlova N, Thompson C . The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 2016; 23(1):27-47. PMC: 4715268. DOI: 10.1016/j.cmet.2015.12.006. View

13.

Yang J, Waldron R, Su H, Moro A, Chang H, Eibl G . Insulin promotes proliferation and fibrosing responses in activated pancreatic stellate cells. Am J Physiol Gastrointest Liver Physiol. 2016; 311(4):G675-G687. PMC: 5142202. DOI: 10.1152/ajpgi.00251.2016. View

14.

Ozdemir B, Pentcheva-Hoang T, Carstens J, Zheng X, Wu C, Simpson T . Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell. 2014; 25(6):719-34. PMC: 4180632. DOI: 10.1016/j.ccr.2014.04.005. View

15.

Nobili V, Alisi A, Musso G, Scorletti E, Calder P, Byrne C . Omega-3 fatty acids: Mechanisms of benefit and therapeutic effects in pediatric and adult NAFLD. Crit Rev Clin Lab Sci. 2015; 53(2):106-20. DOI: 10.3109/10408363.2015.1092106. View

16.

Jiao L, Berrington de Gonzalez A, Hartge P, Pfeiffer R, Park Y, Freedman D . Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts. Cancer Causes Control. 2010; 21(8):1305-14. PMC: 2904431. DOI: 10.1007/s10552-010-9558-x. View

17.

Eguchi K, Nagai R . Islet inflammation in type 2 diabetes and physiology. J Clin Invest. 2017; 127(1):14-23. PMC: 5199688. DOI: 10.1172/JCI88877. View

18.

Yang Y, Rustgi A . Impact of Metformin on Advanced Pancreatic Cancer Survival: Too Little, Too Late?. Clin Cancer Res. 2015; 22(5):1031-3. PMC: 4775394. DOI: 10.1158/1078-0432.CCR-15-2494. View

19.

Preziosi G, Oben J, Fusai G . Obesity and pancreatic cancer. Surg Oncol. 2014; 23(2):61-71. DOI: 10.1016/j.suronc.2014.02.003. View

20.

Teucher B, Rohrmann S, Kaaks R . Obesity: focus on all-cause mortality and cancer. Maturitas. 2009; 65(2):112-6. DOI: 10.1016/j.maturitas.2009.11.018. View