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Diabetes Distilled: Post-pancreatitis diabetes confers a higher risk of pancreatic cancer than type 2 diabetes

Kevin Fernando
This study aimed to explore the impact of type 2 diabetes and pancreatitis, alone and in combination, on the future risk of pancreatic cancer, by interrogating a large nationwide cancer registry linked to hospital discharge and mortality data in New Zealand. The authors found that pancreatitis following a diagnosis of type 2 diabetes increased the risk of pancreatic cancer over 5-fold compared to individuals with type 2 diabetes alone. Furthermore, post-pancreatitis diabetes mellitus (PPDM; diabetes of the exocrine pancreas, also known as type 3c diabetes) conferred the highest risk of pancreatic cancer: a nearly 7-fold increase compared to individuals with type 2 diabetes alone. These findings have significant implications for the targeted screening of pancreatic cancer in people living with type 2 diabetes and a history of pancreatitis, particularly those with PPDM.

Pancreatic cancer is the eleventh most common cancer in England and has a dismal 5-year survival rate less than 7%. Around 60% of individuals are diagnosed at an advanced stage, where the cancer is unresectable, and nearly half are diagnosed through emergency presentation, according to Pancreatic Cancer UK.

Type 2 diabetes is well established as a risk factor for pancreatic cancer, with around a 2-fold increased risk compared to people without type 2 diabetes. Chronic pancreatitis has also been demonstrated as a risk factor for pancreatic cancer, with a near 8-fold increased risk 5 years post-diagnosis compared to those without chronic pancreatitis. The evidence base for acute pancreatitis as a risk factor for pancreatic cancer has also evolved, suggesting around twice the risk compared to the general population. What we lack is evidence informing the combined effect of type 2 diabetes and pancreatitis on the risk of pancreatic cancer.

This large cohort study of nearly 140 000 individuals explored the effect of type 2 diabetes alone, pancreatitis alone, type 2 diabetes followed by pancreatitis, and post-pancreatitis diabetes mellitus (PPDM; diabetes of the exocrine pancreas, also known as type 3c diabetes) on the risk of primary pancreatic cancer. The authors analysed data from the nationwide New Zealand Cancer Registry (NZCR). For the purposes of the study, the NZCR was linked to hospital discharge and mortality databases to obtain comprehensive data on pancreatic cancer. The follow-up period was up to 18 years.

Mean age was 70.4 years in the type 2 diabetes-alone (T2D) group, 70.7 years in the pancreatitis-alone group (PAN), 68 years in the type 2 diabetes followed by pancreatitis group (T2D–PAN) and 68.9 years in the PPDM group. Men accounted for 50.9%, 48.5%, 58.4% and 60.1% in the T2D, PAN, T2D–PAN and PPDM groups, respectively. The average duration of diabetes was 5.3 years in the T2D group, 8.3 years in the T2D–PAN group and 3.4 years in the PPDM group.

Overall, 913 individuals (0.7%) were diagnosed with pancreatic cancer. The rate of pancreatic cancer was 0.6%, 2.0%, 2.3% and 3.1% in the T2D, PAN, T2D–PAN and PPDM groups, respectively.

The PPDM group had the highest adjusted risk of pancreatic cancer, nearly a 7-fold increased risk compared with the T2D group. The T2D–PAN group had an over 5-fold increased risk of pancreatic cancer compared to the T2D group. A head-to-head comparison revealed that the PPDM group had a 2.3-times higher risk of pancreatic cancer than the T2D–PAN group, after adjustments.

These findings suggest that a diagnosis of pancreatitis in people living with type 2 diabetes significantly increases the risk of pancreatic cancer. Moreover, the head-to-head comparison suggests that the timing of diagnosis of pancreatitis is important in determining the risk of pancreatic cancer. Interestingly, these results also suggest that type 2 diabetes alone is not a major risk factor for pancreatic cancer, certainly compared to pancreatitis.

Limitations of this study included the use of hospital discharge data to identify individuals with type 2 diabetes, whereas the majority of type 2 diabetes is diagnosed in primary care. Additionally, the authors acknowledge that data on histological types of pancreatic cancer was incomplete. Finally, the authors could not rule out unmeasured confounders such as obesity, which is also established as a risk factor for pancreatic cancer.

Nevertheless, this high-quality cohort study adds weight to the importance of the early detection of pancreatic cancer to improve the possibility of curative treatment such as pancreatic surgery. Currently there is no evidence or guideline supporting the screening of pancreatic cancer in asymptomatic adults with or without type 2 diabetes. However, perhaps targeted screening in those with type 2 diabetes and pancreatitis should be considered.

Click here to read the publication.

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