Diabetes and pancreatic cancer

Type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer after cigarette smoking and obesity

• epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5- to 2.0-fold increase in the risk of pancreatic cancer
  • a causal relationship between diabetes and pancreatic cancer is also supported by findings from prediagnostic evaluations of glucose and insulin levels in prospective studies (1)
  • insulin resistance and associated hyperglycemia, hyperinsulinemia, and inflammation have been suggested to be the underlying mechanisms contributing to development of diabetes-associated pancreatic cancer

New-onset diabetes may indicate subclinical pancreatic cancer, and patients with new-onset diabetes may constitute a population in whom pancreatic cancer can be detected early (1)

• been reported that the prevalence of diabetes and impaired glucose tolerance in pancreatic cancer cases is as high as 80% (1,2)
  • in the majority of cases, diabetes associated with pancreatic cancer is diagnosed fewer than 2 years prior to the cancer diagnosis or during the cancer course
  • among patients with early-stage pancreatic cancer, diabetes has developed more often in patients with carcinoma of the head of the pancreas than in those with carcinoma of the body and/or tail of the organ
    • the reasons why diabetes develops in patients with pancreatic cancer remains unclear
• older subjects with new-onset diabetes have an approximately 8 fold higher risk of having pancreatic cancer compared to the general population (2)
  
  
• studies examining the association between diabetes and pancreatic cancer suggests that while long-standing diabetes is an etiologic factor for pancreatic cancer, new-onset diabetes is its manifestation (2)
  
  
• majority of pancreatic cancer-associated diabetes is of recent onset, beginning up to two years preceding the diagnosis of cancer (2)
  
  
• new-onset diabetes have a higher probability of subsequently being diagnosed with pancreatic cancer (3)
  • in a population based cohort of 2,122 diabetic individuals in Olmsted County, MN, we determined that 18 (0.8%) new-onset diabetic individuals aged 50 or older were diagnosed with pancreatic cancer within 3 years of meeting criteria for diabetes and the observed-to-expected ratio of pancreatic cancer in this cohort of newly diagnosed diabetes subjects was 7.9 (95% confidence interval [CI] 4.7-12.5)
    
    
• there is a marked and continuous increase in prevalence of diabetes from 24 to 36 months preceding the diagnosis of pancreatic cancer and leading up to the time of diagnosis (2)
  
  
• nearly half the patients with early stage, resectable tumors have diabetes (2)

Pancreatic ductal adenocarcinoma is most frequently detected at an advanced stage (4)

• 5-year survival rate of 3-15%
• people with long-standing type 2 diabetes (more than 5 years) have a 1-1.5-fold increased risk of pancreatic ductal adenocarcinoma compared with the general population
• in individuals who have had type 2 diabetes for less than 1 year, the relative risk of pancreatic ductal adenocarcinoma increases to 5.4-fold
• when diagnosed with pancreatic ductal adenocarcinoma, around 80% of patients have abnormal fasting glucose or glucose intolerance
• diabetes experienced by most patients with pancreatic ductal adenocarcinoma is of recent onset (diagnosed less than 24-36 months before diagnosis of pancreatic ductal adenocarcinoma)
• approximately 0·8-1% of individuals aged over 50 years with new-onset diabetes have diabetes secondary to pancreatic ductal adenocarcinoma

Reference:

• Li D. Diabetes and pancreatic cancer. Mol Carcinog. 2012;51(1):64-74. doi:10.1002/mc.20771
• 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.doi:10.1016/S1470-2045(08)70337-1
• Chari ST, Liebson CL, de Andrade M, Rabe KG, Ransom JE, Petersen GM. Probability of pancreatic cancer following diabetes: A population-based study. Gastroenterology. 2005;129(2):504-511.
• Pereira SP, Oldfield L, Ney A, Hart PA, Keane MG, Pandol SJ, Li D, Greenhalf W, Jeon CY, Koay EJ, Almario CV, Halloran C, Lennon AM, Costello E. Early detection of pancreatic cancer. Lancet Gastroenterol Hepatol. 2020 Jul;5(7):698-710.