[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Ferlay  J, Soerjomataram  I, Dikshit  R,  et al.  Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.  Int J Cancer. 2015;136(5):E359-E386.PubMedGoogle ScholarCrossref
Siegel  RL, Miller  KD, Jemal  A.  Cancer statistics, 2017.  CA Cancer J Clin. 2017;67(1):7-30.PubMedGoogle ScholarCrossref
Oh  CM, Won  YJ, Jung  KW,  et al; Community of Population-Based Regional Cancer Registries.  Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2013.  Cancer Res Treat. 2016;48(2):436-450.PubMedGoogle ScholarCrossref
Holmes  HM, Nguyen  HT, Nayak  P, Oh  JH, Escalante  CP, Elting  LS.  Chronic conditions and health status in older cancer survivors.  Eur J Intern Med. 2014;25(4):374-378.PubMedGoogle ScholarCrossref
Lopez  AD, Mathers  CD, Ezzati  M, Jamison  DT, Murray  CJ.  Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data.  Lancet. 2006;367(9524):1747-1757.PubMedGoogle ScholarCrossref
Shin  DW, Ahn  E, Kim  H, Park  S, Kim  YA, Yun  YH.  Non-cancer mortality among long-term survivors of adult cancer in Korea: national cancer registry study.  Cancer Causes Control. 2010;21(6):919-929.PubMedGoogle ScholarCrossref
Barone  BB, Yeh  HC, Snyder  CF,  et al.  Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis.  JAMA. 2008;300(23):2754-2764.PubMedGoogle ScholarCrossref
Vigneri  P, Frasca  F, Sciacca  L, Pandini  G, Vigneri  R.  Diabetes and cancer.  Endocr Relat Cancer. 2009;16(4):1103-1123.PubMedGoogle ScholarCrossref
Tsilidis  KK, Kasimis  JC, Lopez  DS, Ntzani  EE, Ioannidis  JP.  Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies.  BMJ. 2015;350:g7607.PubMedGoogle ScholarCrossref
Everhart  J, Wright  D.  Diabetes mellitus as a risk factor for pancreatic cancer: a meta-analysis.  JAMA. 1995;273(20):1605-1609.PubMedGoogle ScholarCrossref
Larsson  SC, Orsini  N, Wolk  A.  Diabetes mellitus and risk of colorectal cancer: a meta-analysis.  J Natl Cancer Inst. 2005;97(22):1679-1687.PubMedGoogle ScholarCrossref
Larsson  SC, Mantzoros  CS, Wolk  A.  Diabetes mellitus and risk of breast cancer: a meta-analysis.  Int J Cancer. 2007;121(4):856-862.PubMedGoogle ScholarCrossref
Wang  C, Wang  X, Gong  G,  et al.  Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies.  Int J Cancer. 2012;130(7):1639-1648.PubMedGoogle ScholarCrossref
Currie  CJ, Poole  CD, Jenkins-Jones  S, Gale  EA, Johnson  JA, Morgan  CL.  Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival.  Diabetes Care. 2012;35(2):299-304.PubMedGoogle ScholarCrossref
Lipscombe  LL, Chan  WW, Yun  L, Austin  PC, Anderson  GM, Rochon  PA.  Incidence of diabetes among postmenopausal breast cancer survivors.  Diabetologia. 2013;56(3):476-483.PubMedGoogle ScholarCrossref
De Bruijn  KM, van Eijck  CH.  New-onset diabetes after distal pancreatectomy: a systematic review.  Ann Surg. 2015;261(5):854-861.PubMedGoogle ScholarCrossref
Singh  S, Earle  CC, Bae  SJ,  et al.  Incidence of diabetes in colorectal cancer survivors.  J Natl Cancer Inst. 2016;108(6):djv402.PubMedGoogle ScholarCrossref
Giovannucci  E, Harlan  DM, Archer  MC,  et al.  Diabetes and cancer: a consensus report.  Diabetes Care. 2010;33(7):1674-1685.PubMedGoogle ScholarCrossref
Lee  J, Lee  JS, Park  SH, Shin  SA, Kim  K.  Cohort profile: the National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea.  Int J Epidemiol. 2017. 46(2):e15.PubMedGoogle Scholar
National Health Insurance Service (NHIS).  National Health Examination Statistical Yearbook. Seoul, Korea: NHIS; 2014.
Chun  C-B, Kim  S-Y, Lee  J-Y, Lee  S-Y.  Republic of Korea: health system review.  Health Syst Transit. 2009;11(7).Google Scholar
Korea Pharmaceutical Information Service. Korea Pharmaceutical Information. http://biz.kpis.or.kr. Accessed June 14, 2016.
Shin  DW, Cho  B, Guallar  E.  Korean National Health Insurance database.  JAMA Intern Med. 2016;176(1):138.PubMedGoogle ScholarCrossref
Charlson  ME, Pompei  P, Ales  KL, MacKenzie  CR.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.  J Chronic Dis. 1987;40(5):373-383.PubMedGoogle ScholarCrossref
Kim  KH.  Comparative study on three algorithms of the ICD-10 Charlson comorbidity index with myocardial infarction patients [in Korean].  J Prev Med Public Health. 2010;43(1):42-49.PubMedGoogle ScholarCrossref
Fine  JP, Gray  RJ.  A proportional hazards model for the subdistribution of a competing risk.  J Am Stat Assoc. 1999;94(446):496-509.Google ScholarCrossref
Wooldridge  JE, Anderson  CM, Perry  MC.  Corticosteroids in advanced cancer.  Oncology (Williston Park). 2001;15(2):225-234.PubMedGoogle Scholar
Greenstein  S, Ghias  K, Krett  NL, Rosen  ST.  Mechanisms of glucocorticoid-mediated apoptosis in hematological malignancies.  Clin Cancer Res. 2002;8(6):1681-1694.PubMedGoogle Scholar
Yennurajalingam  S, Frisbee-Hume  S, Palmer  JL,  et al.  Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer.  J Clin Oncol. 2013;31(25):3076-3082.PubMedGoogle ScholarCrossref
Clore  JN, Thurby-Hay  L.  Glucocorticoid-induced hyperglycemia.  Endocr Pract. 2009;15(5):469-474.PubMedGoogle ScholarCrossref
Lee  SY, Kurita  N, Yokoyama  Y,  et al.  Glucocorticoid-induced diabetes mellitus in patients with lymphoma treated with CHOP chemotherapy.  Support Care Cancer. 2014;22(5):1385-1390.PubMedGoogle ScholarCrossref
Harris  D, Barts  A, Connors  J,  et al.  Glucocorticoid-induced hyperglycemia is prevalent and unpredictable for patients undergoing cancer therapy: an observational cohort study.  Curr Oncol. 2013;20(6):e532-e538.PubMedGoogle ScholarCrossref
Lowas  SR, Marks  D, Malempati  S.  Prevalence of transient hyperglycemia during induction chemotherapy for pediatric acute lymphoblastic leukemia.  Pediatr Blood Cancer. 2009;52(7):814-818.PubMedGoogle ScholarCrossref
Feng  JP, Yuan  XL, Li  M,  et al.  Secondary diabetes associated with 5-fluorouracil-based chemotherapy regimens in non-diabetic patients with colorectal cancer: results from a single-centre cohort study.  Colorectal Dis. 2013;15(1):27-33.PubMedGoogle ScholarCrossref
Mohn  A, Di Marzio  A, Capanna  R, Fioritoni  G, Chiarelli  F.  Persistence of impaired pancreatic beta-cell function in children treated for acute lymphoblastic leukaemia.  Lancet. 2004;363(9403):127-128.PubMedGoogle ScholarCrossref
Ariaans  G, de Jong  S, Gietema  JA, Lefrandt  JD, de Vries  EG, Jalving  M.  Cancer-drug induced insulin resistance: innocent bystander or unusual suspect.  Cancer Treat Rev. 2015;41(4):376-384.PubMedGoogle ScholarCrossref
Hwangbo  Y, Lee  EK.  Acute hyperglycemia associated with anti-cancer medication.  Endocrinol Metab (Seoul). 2017;32(1):23-29.PubMedGoogle ScholarCrossref
Yoshida  H, Imamura  T, Saito  AM,  et al; Japan Association of Childhood Leukemia Study.  Protracted administration of L-asparaginase in maintenance phase is the risk factor for hyperglycemia in older patients with pediatric acute lymphoblastic leukemia.  PLoS One. 2015;10(8):e0136428.PubMedGoogle ScholarCrossref
Meacham  LR, Sklar  CA, Li  S,  et al.  Diabetes mellitus in long-term survivors of childhood cancer. increased risk associated with radiation therapy: a report for the Childhood Cancer Survivor study.  Arch Intern Med. 2009;169(15):1381-1388.PubMedGoogle ScholarCrossref
Davidson  J, Wilkinson  A, Dantal  J,  et al; International Expert Panel.  New-onset diabetes after transplantation: 2003 international consensus guidelines. proceedings of an international expert panel meeting. Barcelona, Spain, 19 February 2003.  Transplantation. 2003;75(10)(suppl):SS3-SS24.PubMedGoogle Scholar
Lipscombe  LL, Fischer  HD, Yun  L,  et al.  Association between tamoxifen treatment and diabetes: a population-based study.  Cancer. 2012;118(10):2615-2622.PubMedGoogle ScholarCrossref
Argilés  JM, Busquets  S, Stemmler  B, López-Soriano  FJ.  Cancer cachexia: understanding the molecular basis.  Nat Rev Cancer. 2014;14(11):754-762.PubMedGoogle ScholarCrossref
Honors  MA, Kinzig  KP.  The role of insulin resistance in the development of muscle wasting during cancer cachexia.  J Cachexia Sarcopenia Muscle. 2012;3(1):5-11.PubMedGoogle ScholarCrossref
Fearon  KC, Glass  DJ, Guttridge  DC.  Cancer cachexia: mediators, signaling, and metabolic pathways.  Cell Metab. 2012;16(2):153-166.PubMedGoogle ScholarCrossref
Porporato  PE.  Understanding cachexia as a cancer metabolism syndrome.  Oncogenesis. 2016;5:e200.PubMedGoogle ScholarCrossref
Dungan  KM, Braithwaite  SS, Preiser  JC.  Stress hyperglycaemia.  Lancet. 2009;373(9677):1798-1807.PubMedGoogle ScholarCrossref
Gornik  I, Vujaklija-Brajkovic  A, Renar  IP, Gasparovic  V.  A prospective observational study of the relationship of critical illness associated hyperglycaemia in medical ICU patients and subsequent development of type 2 diabetes.  Crit Care. 2010;14(4):R130.PubMedGoogle ScholarCrossref
Shirakawa  S, Matsumoto  I, Toyama  H,  et al.  Pancreatic volumetric assessment as a predictor of new-onset diabetes following distal pancreatectomy.  J Gastrointest Surg. 2012;16(12):2212-2219.PubMedGoogle ScholarCrossref
de Vathaire  F, El-Fayech  C, Ben Ayed  FF,  et al.  Radiation dose to the pancreas and risk of diabetes mellitus in childhood cancer survivors: a retrospective cohort study.  Lancet Oncol. 2012;13(10):1002-1010.PubMedGoogle ScholarCrossref
Pannala  R, Basu  A, Petersen  GM, Chari  ST.  New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer.  Lancet Oncol. 2009;10(1):88-95.PubMedGoogle ScholarCrossref
Garcia-Compean  D, Jaquez-Quintana  JO, Gonzalez-Gonzalez  JA, Maldonado-Garza  H.  Liver cirrhosis and diabetes: risk factors, pathophysiology, clinical implications and management.  World J Gastroenterol. 2009;15(3):280-288.PubMedGoogle ScholarCrossref
Elkrief  L, Rautou  PE, Sarin  S, Valla  D, Paradis  V, Moreau  R.  Diabetes mellitus in patients with cirrhosis: clinical implications and management.  Liver Int. 2016;36(7):936-948.PubMedGoogle ScholarCrossref
Huang  WC, Levey  AS, Serio  AM,  et al.  Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study.  Lancet Oncol. 2006;7(9):735-740.PubMedGoogle ScholarCrossref
Shehab-Eldin  W, Shoeb  S, Khamis  S, Salah  Y, Shoker  A.  Susceptibility to insulin resistance after kidney donation: a pilot observational study.  Am J Nephrol. 2009;30(4):371-376.PubMedGoogle ScholarCrossref
Renehan  AG, Frystyk  J, Flyvbjerg  A.  Obesity and cancer risk: the role of the insulin-IGF axis.  Trends Endocrinol Metab. 2006;17(8):328-336.PubMedGoogle ScholarCrossref
Parry  C, Kent  EE, Mariotto  AB, Alfano  CM, Rowland  JH.  Cancer survivors: a booming population.  Cancer Epidemiol Biomarkers Prev. 2011;20(10):1996-2005.PubMedGoogle ScholarCrossref
Original Investigation
August 2018

Incidence of Diabetes After Cancer Development: A Korean National Cohort Study

Author Affiliations
  • 1Division of Endocrinology, Department of Internal Medicine, National Cancer Center, Goyang, South Korea
  • 2Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
  • 3Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • 4National Cancer Control Institute, National Cancer Center, Goyang, South Korea
  • 5Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, South Korea
  • 6Translational Epidemiology Research Branch, Research Institute, National Cancer Center, Goyang, South Korea
  • 7Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea
  • 8Center for Liver Cancer, National Cancer Center, Goyang, South Korea
  • 9Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • 10Department of Epidemiology, and Welch Center for Epidemiology, Prevention, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 11National Center for Epidemiology, Instituto de Salud Carlos III, and Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain
  • 12Department of Laboratory Medicine, Hospital, National Cancer Center, Goyang, South Korea
JAMA Oncol. 2018;4(8):1099-1105. doi:10.1001/jamaoncol.2018.1684
Key Points

Question  Does cancer increase the risk of diabetes?

Findings  In a Korean general population cohort of 524 089 men and women observed for up to 10 years, participants who developed cancer had a clear increase in the subsequent risk of diabetes, even after taking into account precancer risk factors.

Meaning  Physicians should remember that patients with cancer develop other clinical problems, such as diabetes, with higher frequency than individuals without cancer, and should consider routine diabetes screening in these patients.


Importance  Diabetes is an established risk factor for developing cancer. A limited body of evidence also suggests that cancer can increase the risk of developing new cases of diabetes, but the evidence is inconclusive.

Objective  To evaluate whether the development of cancer is associated with increasing risk of subsequent diabetes.

Design, Setting, and Participants  This cohort study included a nationally representative sample of the Korean general population observed for up to 10 years (January 1, 2003, to December 31, 2013). A total of 524 089 men and women 20 to 70 years of age without diabetes and with no history of cancer at baseline were included.

Exposures  Incident cancer (time-varying exposure).

Main Outcomes and Measures  Incident type 2 diabetes using insurance claim codes.

Results  During 3 492 935.6 person-years of follow-up (median follow-up, 7.0 years) in 494 189 individuals (50.0% female; mean [SD] age, 41.8 [12.5] years), 15 130 participants developed cancer and 26 610 participants developed diabetes. After adjustment for age, sex, precancer diabetes risk factors, metabolic factors, and comorbidities, the hazard ratio (HR) for diabetes associated with cancer development was 1.35 (95% CI, 1.26-1.45; P < .001). The excess risk for diabetes was highest in the first 2 years after cancer diagnosis, but it remained elevated throughout follow-up. By cancer type, development of pancreatic (HR, 5.15; 95% CI, 3.32-7.99), kidney (HR, 2.06; 95% CI, 1.34-3.16), liver (HR, 1.95; 95% CI, 1.50-2.54), gallbladder (HR, 1.79; 95% CI, 1.08-2.98), lung (HR, 1.74; 95% CI, 1.34-2.24), blood (HR, 1.61; 95% CI, 1.07-2.43), breast (HR, 1.60; 95% CI, 1.27-2.01), stomach (HR, 1.35; 95% CI, 1.16-1.58), and thyroid cancer (HR, 1.33; 95% CI, 1.12-1.59) was associated with a significantly increased risk of diabetes.

Conclusions and Relevance  In this large Korean cohort, cancer development increased the risk of subsequent diabetes. These data provide evidence that cancer is associated with an increased risk of diabetes in cancer survivors independent of traditional diabetes risk factors. Physicians should remember that patients with cancer develop other clinical problems, such as diabetes, with higher frequency than individuals without cancer, and should consider routine diabetes screening in these patients.