Research progress of correlation between pancreatic cancer and diabetes mellitus_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Jie ,  CHEN Qilong

Department of Pancreatic Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, P. R. China;

Corresponding author：

CHEN Qilong, Email: chenqilong651003@sohu.com

Keywords：

pancreatic cancer; diabetes mellitus; insulin resistance; risk factor; review

DOI：

10.7507/1007-9424.201905043

Video：

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Objective To summarize the research progress of correlation between pancreatic cancer and diabetes mellitus.Methods Recent studies on the association between pancreatic cancer and diabetes mellitus were extensively reviewed, and relevant research results on the association between pancreatic cancer and diabetes mellitus were reviewed.Results Pancreatic cancer had a particular association with diabetes. Patients with pancreatic cancer may develop new diabetes or worsen existing diabetes mellitus. About 50% of patients with pancreatic cancer had diabetes mellitus before diagnosis, suggesting a “dual causal relationship” between pancreatic cancer and diabetes mellitus. Long-term type 2 diabetes mellitus (T2DM) was one of the high risk factors for the occurrence and development of pancreatic cancer. T2DM may also increase the risk of pancreatic cancer due to hyperinsulinemia, adipokine, and other factors. Pancreatic cancer was one of the cause of diabetes mellitus at the same time, but its mechanism was not yet known, also needed to get a lot of information to understand the impact of long-term diabetes mellitus on the development of pancreatic cancer, as well as the reason of pancreatic cancer related to diabetes mellitus mechanism.Conclusion The clear relationship between pancreatic cancer and diabetes mellitus has not been proved, and further research is needed to clarify the relationship between them.

Citation： WANG Jie, CHEN Qilong. Research progress of correlation between pancreatic cancer and diabetes mellitus. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(2): 245-251. doi: 10.7507/1007-9424.201905043 Copy

1.	Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol, 2019, 10(1): 10-27.
2.	Chen W, Sun K, Zheng R, et al. Cancer incidence and mortality in China, 2014. Chin J Cancer Res, 2018, 30(1): 1-12.
3.	Li D, Morris JS, Liu J, et al. Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA, 2009, 301(24): 2553-2562.
4.	Boursi B, Finkelman B, Giantonio BJ, et al. A Clinical prediction model to assess risk for pancreatic cancer among patients with new-onset diabetes. Gastroenterology, 2017, 152(4): 840-850.
5.	Balzano G, Dugnani E, Gandolfi A, et al. Effect of diabetes on survival after resection of pancreatic adenocarcinoma. a prospective, observational study. PLoS One, 2016, 11(11): e0166008.
6.	Pothuraju R, Rachagani S, Junker WM, et al. Pancreatic cancer associated with obesity and diabetes: an alternative approach for its targeting. J Exp Clin Cancer Res, 2018, 37(1): 319.
7.	Aggarwal G, Rabe KG, Petersen GM, et al. New-onset diabetes in pancreatic cancer: a study in the primary care setting. Pancreatology, 2012, 12(2): 156-161.
8.	Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia, 2003, 46(1): 3-19.
9.	Dooley J, Tian L, Schonefeldt S, et al. Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes. Nat Genet, 2016, 48(5): 519-527.
10.	Kleeff J, Costello E, Jackson R, et al. The impact of diabetes mellitus on survival following resection and adjuvant chemotherapy for pancreatic cancer. Br J Cancer, 2016, 115(7): 887-894.
11.	Jiang QL, Wang CF, Tian YT, et al. Body mass index does not affect the survival of pancreatic cancer patients. World J Gastroenterol, 2017, 23(34): 6287-6293.
12.	Leclerc E, Vetter SW. The role of S100 proteins and their receptor RAGE in pancreatic cancer. Biochim Biophys Acta, 2015, 1852(12): 2706-2711.
13.	Kang R, Hou W, Zhang Q, et al. RAGE is essential for oncogenic KRAS-mediated hypoxic signaling in pancreatic cancer. Cell Death Dis, 2014, 5: e1480.
14.	Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer, 2015, 15(8): 484-498.
15.	Park J, Morley TS, Kim M, et al. Obesity and cancer-mechanisms underlying tumour progression and recurrence. Nat Rev Endocrinol, 2014, 10(8): 455-465.
16.	Vongsuvanh R, George J, Qiao L, et al. Visceral adiposity in gastrointestinal and hepatic carcinogenesis. Cancer Lett, 2013, 330(1): 1-10.
17.	戚远, 余宏铸. 血管形成相关因子与胰腺癌浸润、转移关系的研究进展. 安徽医学, 2013, 34(2): 224-226.
18.	Pannala R, Leirness JB, Bamlet WR, et al. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology, 2008, 134(4): 981-987.
19.	Chari ST, Leibson CL, Rabe KG, et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology, 2008, 134(1): 95-101.
20.	He XY, Li JF, Yao WY, et al. Resolution of new-onset diabetes after radical pancreatic resection predicts long-term survival in patients with pancreatic ductal cell adenocarcinoma. Ann Surg Oncol, 2013, 20(12): 3809-3816.
21.	Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature, 2006, 444(7121): 840-846.
22.	Chari ST, Zapiach M, Yadav D, et al. Beta-cell function and insulin resistance evaluated by HOMA in pancreatic cancer subjects with varying degrees of glucose intolerance. Pancreatology, 2005, 5(2-3): 229-233.
23.	Basso D, Greco E, Fogar P, et al. Pancreatic cancer-derivedS-100A8 N-terminal peptide: a diabetes cause? Clin Chim Acta, 2006, 372(1-2): 120-128.
24.	Xia H, Gilbertsen A, Herrera J, et al. Calcium-binding protein S100A4 confers mesenchymal progenitor cell fibrogenicity in idiopathic pulmonary fibrosis. J Clin Invest, 2017, 127(7): 2586-2597.
25.	Aggarwal G, Ramachandran V, Javeed N, et al. Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice. Gastroenterology, 2012, 143(6): 1510-1517.e1.
26.	Hong Y, Hay DL, Quirion R, et al. The pharmacology of adrenomedullin 2/intermedin. Br J Pharmacol, 2012, 166(1): 110-120.
27.	Tan MH, Iyengar R, Mizokami-Stout K, et al. Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports. Clin Diabetes Endocrinol, 2019, 5: 1.
28.	Könner AC, Brüning JC. Selective insulin and leptin resistance in metabolic disorders. Cell Metab, 2012, 16(2): 144-152.
29.	Miller MS, Allen P, Brentnall TA, et al. Pancreatic cancer chemoprevention translational workshop: meeting report. Pancreas, 2016, 45(8): 1080-1091.
30.	Isaksson B, Strömmer L, Friess H, et al. Impaired insulin action on phosphatidylinositol 3-kinase activity and glucose transport in skeletal muscle of pancreatic cancer patients. Pancreas, 2003, 26(2): 173-177.
31.	Evans JM, Donnelly LA, Emslie-Smith AM, et al. Metformin and reduced risk of cancer in diabetic patients. BMJ, 2005, 330(7503): 1304-1305.
32.	Bowker SL, Majumdar SR, Veugelers P, et al. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care, 2006, 29(2): 254-258.
33.	Bosetti C, Rosato V, Li D, et al. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol, 2014, 25(10): 2065-2072.
34.	Sadeghi N, Abbruzzese JL, Yeung SC, et al. Metformin use is associated with better survival of diabetic patients with pancreatic cancer. Clin Cancer Res, 2012, 18(10): 2905-2912.
35.	Lee LS, Andersen DK, Ashida R, et al. EUS and related technologies for the diagnosis and treatment of pancreatic disease: research gaps and opportunities-summary of a National Institute of Diabetes and Digestive and Kidney Diseases workshop. Gastrointest Endosc, 2017, 86(5): 768-778.
36.	Singh S, Singh PP, Singh AG, et al. Anti-diabetic medications and risk of pancreatic cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Am J Gastroenterol, 2013, 108(4): 510-519.
37.	Fasih A, Elbaz HA, Hüttemann M, et al. Radiosensitization of pancreatic cancer cells by metformin through the AMPK pathway. Radiat Res, 2014, 182(1): 50-59.
38.	Zhang JG, Hong DF, Zhang CW, et al. Sirtuin 1 facilitates chemoresistance of pancreatic cancer cells by regulating adaptive response to chemotherapy-induced stress. Cancer Sci, 2014, 105(4): 445-454.

1. Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol, 2019, 10(1): 10-27.
2. Chen W, Sun K, Zheng R, et al. Cancer incidence and mortality in China, 2014. Chin J Cancer Res, 2018, 30(1): 1-12.
3. Li D, Morris JS, Liu J, et al. Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA, 2009, 301(24): 2553-2562.
4. Boursi B, Finkelman B, Giantonio BJ, et al. A Clinical prediction model to assess risk for pancreatic cancer among patients with new-onset diabetes. Gastroenterology, 2017, 152(4): 840-850.
5. Balzano G, Dugnani E, Gandolfi A, et al. Effect of diabetes on survival after resection of pancreatic adenocarcinoma. a prospective, observational study. PLoS One, 2016, 11(11): e0166008.
6. Pothuraju R, Rachagani S, Junker WM, et al. Pancreatic cancer associated with obesity and diabetes: an alternative approach for its targeting. J Exp Clin Cancer Res, 2018, 37(1): 319.
7. Aggarwal G, Rabe KG, Petersen GM, et al. New-onset diabetes in pancreatic cancer: a study in the primary care setting. Pancreatology, 2012, 12(2): 156-161.
8. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia, 2003, 46(1): 3-19.
9. Dooley J, Tian L, Schonefeldt S, et al. Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes. Nat Genet, 2016, 48(5): 519-527.
10. Kleeff J, Costello E, Jackson R, et al. The impact of diabetes mellitus on survival following resection and adjuvant chemotherapy for pancreatic cancer. Br J Cancer, 2016, 115(7): 887-894.
11. Jiang QL, Wang CF, Tian YT, et al. Body mass index does not affect the survival of pancreatic cancer patients. World J Gastroenterol, 2017, 23(34): 6287-6293.
12. Leclerc E, Vetter SW. The role of S100 proteins and their receptor RAGE in pancreatic cancer. Biochim Biophys Acta, 2015, 1852(12): 2706-2711.
13. Kang R, Hou W, Zhang Q, et al. RAGE is essential for oncogenic KRAS-mediated hypoxic signaling in pancreatic cancer. Cell Death Dis, 2014, 5: e1480.
14. Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer, 2015, 15(8): 484-498.
15. Park J, Morley TS, Kim M, et al. Obesity and cancer-mechanisms underlying tumour progression and recurrence. Nat Rev Endocrinol, 2014, 10(8): 455-465.
16. Vongsuvanh R, George J, Qiao L, et al. Visceral adiposity in gastrointestinal and hepatic carcinogenesis. Cancer Lett, 2013, 330(1): 1-10.
17. 戚远, 余宏铸. 血管形成相关因子与胰腺癌浸润、转移关系的研究进展. 安徽医学, 2013, 34(2): 224-226.
18. Pannala R, Leirness JB, Bamlet WR, et al. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology, 2008, 134(4): 981-987.
19. Chari ST, Leibson CL, Rabe KG, et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology, 2008, 134(1): 95-101.
20. He XY, Li JF, Yao WY, et al. Resolution of new-onset diabetes after radical pancreatic resection predicts long-term survival in patients with pancreatic ductal cell adenocarcinoma. Ann Surg Oncol, 2013, 20(12): 3809-3816.
21. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature, 2006, 444(7121): 840-846.
22. Chari ST, Zapiach M, Yadav D, et al. Beta-cell function and insulin resistance evaluated by HOMA in pancreatic cancer subjects with varying degrees of glucose intolerance. Pancreatology, 2005, 5(2-3): 229-233.
23. Basso D, Greco E, Fogar P, et al. Pancreatic cancer-derivedS-100A8 N-terminal peptide: a diabetes cause? Clin Chim Acta, 2006, 372(1-2): 120-128.
24. Xia H, Gilbertsen A, Herrera J, et al. Calcium-binding protein S100A4 confers mesenchymal progenitor cell fibrogenicity in idiopathic pulmonary fibrosis. J Clin Invest, 2017, 127(7): 2586-2597.
25. Aggarwal G, Ramachandran V, Javeed N, et al. Adrenomedullin is up-regulated in patients with pancreatic cancer and causes insulin resistance in β cells and mice. Gastroenterology, 2012, 143(6): 1510-1517.e1.
26. Hong Y, Hay DL, Quirion R, et al. The pharmacology of adrenomedullin 2/intermedin. Br J Pharmacol, 2012, 166(1): 110-120.
27. Tan MH, Iyengar R, Mizokami-Stout K, et al. Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports. Clin Diabetes Endocrinol, 2019, 5: 1.
28. Könner AC, Brüning JC. Selective insulin and leptin resistance in metabolic disorders. Cell Metab, 2012, 16(2): 144-152.
29. Miller MS, Allen P, Brentnall TA, et al. Pancreatic cancer chemoprevention translational workshop: meeting report. Pancreas, 2016, 45(8): 1080-1091.
30. Isaksson B, Strömmer L, Friess H, et al. Impaired insulin action on phosphatidylinositol 3-kinase activity and glucose transport in skeletal muscle of pancreatic cancer patients. Pancreas, 2003, 26(2): 173-177.
31. Evans JM, Donnelly LA, Emslie-Smith AM, et al. Metformin and reduced risk of cancer in diabetic patients. BMJ, 2005, 330(7503): 1304-1305.
32. Bowker SL, Majumdar SR, Veugelers P, et al. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care, 2006, 29(2): 254-258.
33. Bosetti C, Rosato V, Li D, et al. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol, 2014, 25(10): 2065-2072.
34. Sadeghi N, Abbruzzese JL, Yeung SC, et al. Metformin use is associated with better survival of diabetic patients with pancreatic cancer. Clin Cancer Res, 2012, 18(10): 2905-2912.
35. Lee LS, Andersen DK, Ashida R, et al. EUS and related technologies for the diagnosis and treatment of pancreatic disease: research gaps and opportunities-summary of a National Institute of Diabetes and Digestive and Kidney Diseases workshop. Gastrointest Endosc, 2017, 86(5): 768-778.
36. Singh S, Singh PP, Singh AG, et al. Anti-diabetic medications and risk of pancreatic cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Am J Gastroenterol, 2013, 108(4): 510-519.
37. Fasih A, Elbaz HA, Hüttemann M, et al. Radiosensitization of pancreatic cancer cells by metformin through the AMPK pathway. Radiat Res, 2014, 182(1): 50-59.
38. Zhang JG, Hong DF, Zhang CW, et al. Sirtuin 1 facilitates chemoresistance of pancreatic cancer cells by regulating adaptive response to chemotherapy-induced stress. Cancer Sci, 2014, 105(4): 445-454.

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