Korean J Gastroenterol.  2013 Nov;62(5):263-266. 10.4166/kjg.2013.62.5.263.

New-onset Diabetes as an Early Sign of Pancreatic Cancer

Affiliations
  • 1Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. jongk.lee@samsung.com

Abstract

While long-standing diabetes is a risk factor of pancreatic cancer, new-onset diabetes could be a consequence of underlying pancreatic malignancy. About 30% to 50% of pancreatic cancer patients have new-onset diabetes. Because diabetes develops in preclinical or early stages of pancreatic cancer, it could serve as an excellent clue for early detection of pancreatic cancer. Insulin resistance associated with hyperglycemia and hyperinsulinemia by diabetogenic factors secreted from cancer cells have been suggested to be a possible mechanism of pancreatic cancer-induced diabetes. It is difficult to differentiate pancreatic cancer-induced diabetes from the more common type 2 diabetes. Although several clinical features and potential biomarkers have been investigated, optimal strategies and modalities to screen pancreatic cancer among the new-onset diabetes have not yet been fully determined.

Keyword

New-onset diabetes; Pancreatic cancer; Diabetogenic factor; Early detection

MeSH Terms

Adiponectin/metabolism
Age Factors
Body Mass Index
Cytokines/metabolism
Diabetes Mellitus, Type 2/*complications/*diagnosis/pathology
Humans
Pancreatic Neoplasms/*complications/*diagnosis/pathology
Tomography, X-Ray Computed
Adiponectin
Cytokines

Reference

References

1. Li D, Tang H, Hassan MM, Holly EA, Bracci PM, Silverman DT. Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies. Cancer Causes Control. 2011; 22:189–197.
Article
2. Li D. Diabetes and pancreatic cancer. Mol Carcinog. 2012; 51:64–74.
Article
3. Ben Q, Xu M, Ning X, et al. Diabetes mellitus and risk of pancreatic cancer: a metaanalysis of cohort studies. Eur J Cancer. 2011; 47:1928–1937.
Article
4. Aggarwal G, Kamada P, Chari ST. Prevalence of diabetes mellitus in pancreatic cancer compared to common cancers. Pancreas. 2013; 42:198–201.
Article
5. Huxley R, Ansary-Moghaddam A, Berrington de González A, Barzi F, Woodward M. Type-II diabetes and pancreatic cancer: a metaanalysis of 36 studies. Br J Cancer. 2005; 92:2076–2083.
Article
6. Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, Tsugane S. Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med. 2006; 166:1871–1877.
7. Everhart J, Wright D. Diabetes mellitus as a risk factor for pancreatic cancer. A metaanalysis. JAMA. 1995; 273:1605–1609.
Article
8. Bonelli L, Aste H, Bovo P, et al. Exocrine pancreatic cancer, cigarette smoking, and diabetes mellitus: a case-control study in northern Italy. Pancreas. 2003; 27:143–149.
Article
9. Maisonneuve P, Lowenfels AB, Bueno-de-Mesquita HB, et al. Past medical history and pancreatic cancer risk: results from a multicenter case-control study. Ann Epidemiol. 2010; 20:92–98.
Article
10. Ding XZ, Fehsenfeld DM, Murphy LO, Permert J, Adrian TE. Physiological concentrations of insulin augment pancreatic cancer cell proliferation and glucose utilization by activating MAP kinase, PI3 kinase and enhancing GLUT-1 expression. Pancreas. 2000; 21:310–320.
Article
11. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005; 330:1304–1305.
Article
12. Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009; 137:482–488.
Article
13. Rozengurt E, Sinnett-Smith J, Kisfalvi K. Crosstalk between insulin/insulin-like growth factor-1 receptors and G protein-cou-pled receptor signaling systems: a novel target for the anti-diabetic drug metformin in pancreatic cancer. Clin Cancer Res. 2010; 16:2505–2511.
14. Michaud DS, Liu S, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study. J Natl Cancer Inst. 2002; 94:1293–1300.
Article
15. Stolzenberg-Solomon RZ, Graubard BI, Chari S, et al. Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. JAMA. 2005; 294:2872–2878.
Article
16. Frasca F, Pandini G, Sciacca L, et al. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem. 2008; 114:23–37.
Article
17. Kornmann M, Maruyama H, Bergmann U, et al. Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer. Cancer Res. 1998; 58:4250–4254.
18. Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008; 8:915–928.
Article
19. Han L, Ma Q, Li J, et al. High glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and trans-activation of EGFR. PLoS One. 2011; 6:e27074.
Article
20. Cui Y, Andersen DK. Diabetes and pancreatic cancer. Endocr Relat Cancer. 2012; 19:F9–F26.
Article
21. Bao Y, Giovannucci EL, Kraft P, et al. A prospective study of plasma adiponectin and pancreatic cancer risk in five US cohorts. J Natl Cancer Inst. 2013; 105:95–103.
Article
22. Chari ST, Leibson CL, Rabe KG, et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology. 2008; 134:95–101.
Article
23. Pannala R, Leirness JB, Bamlet WR, Basu A, Petersen GM, Chari ST. Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology. 2008; 134:981–987.
Article
24. Permert J, Ihse I, Jorfeldt L, von Schenck H, Arnquist HJ, Larsson J. Improved glucose metabolism after subtotal pancreatectomy for pancreatic cancer. Br J Surg. 1993; 80:1047–1050.
Article
25. Tsuchiya R, Noda T, Harada N, et al. Collective review of small carcinomas of the pancreas. Ann Surg. 1986; 203:77–81.
Article
26. Ding X, Flatt PR, Permert J, Adrian TE. Pancreatic cancer cells selectively stimulate islet beta cells to secrete amylin. Gastroenterology. 1998; 114:130–138.
27. Basso D, Greco E, Fogar P, et al. Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause? Clin Chim Acta. 2006; 372:120–128.
Article
28. Chari ST, Klee GG, Miller LJ, Raimondo M, DiMagno EP. Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer. Gastroenterology. 2001; 121:640–645.
Article
29. Pfeffer F, Koczan D, Adam U, et al. Expression of connexin26 in islets of Langerhans is associated with impaired glucose tolerance in patients with pancreatic adenocarcinoma. Pancreas. 2004; 29:284–290.
Article
30. Huang H, Dong X, Kang MX, et al. Novel blood biomarkers of pancreatic cancer-associated diabetes mellitus identified by peripheral blood-based gene expression profiles. Am J Gastroenterol. 2010; 105:1661–1669.
Article
31. Cui Y, Andersen DK. Pancreatogenic diabetes: special considerations for management. Pancreatology. 2011; 11:279–294.
Article
32. Magruder JT, Elahi D, Andersen DK. Diabetes and pancreatic cancer: chicken or egg? Pancreas. 2011; 40:339–351.
33. Ogawa Y, Tanaka M, Inoue K, et al. A prospective pancreato-graphic study of the prevalence of pancreatic carcinoma in patients with diabetes mellitus. Cancer. 2002; 94:2344–2349.
Article
34. Damiano J, Bordier L, Le Berre JP, et al. Should pancreas imaging be recommanded in patients over 50 years when diabetes is discovered because of acute symptoms? Diabetes Metab. 2004; 30:203–207.
Article
35. Lee JH, Kim SA, Park HY, et al. New-onset diabetes patients need pancreatic cancer screening? J Clin Gastroenterol. 2012; 46:e58–e61.
Article
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