What is the relationship between Diabetes Mellitus (DM) and pancreatic cancer?

From the Guidelines

Diabetes Mellitus (DM) is associated with an increased risk of pancreatic cancer, particularly in individuals with new-onset diabetes or long-standing diabetes, and the relationship between the two conditions is bidirectional, with each potentially influencing the development of the other. The association between diabetes and pancreatic cancer is complex, with evidence suggesting that new-onset diabetes, especially in those over 50 years old, may be an early warning sign of pancreatic cancer, as approximately 1% of patients diagnosed with diabetes who are aged 50 years or younger will be diagnosed with pancreatic cancer within 3 years 1. Some key points to consider in this relationship include:

• New-onset diabetes may be caused by the cancer, although the physiologic basis for this effect is not yet completely understood 1
• Long-term diabetes appears to be a risk factor for pancreatic cancer, with some studies showing an association of pancreatic cancer with diabetes of 2- to 8-year duration 1
• The use of diabetic medications such as insulin and sulfonylureas has been found to be associated with an increased risk for pancreatic cancer, while metformin may be associated with a reduced risk for pancreatic and other cancers 1
• Metformin use has been reported to result in higher pancreatic cancer survival in patients with diabetes, with a retrospective analysis of 302 patients with pancreatic cancer and diabetes showing that metformin use was associated with increased survival at 2 years and increased overall survival 1 For diabetic patients, maintaining good glycemic control through medications like metformin at standard doses, regular physical activity, and a balanced diet is important, and regular screening is not currently recommended for all diabetic patients, but those with additional risk factors should discuss with their healthcare provider about appropriate monitoring 1. The pancreatic cancer-diabetes link likely stems from the tumor's ability to cause insulin resistance and beta-cell dysfunction even before the cancer becomes clinically detectable, while the chronic inflammatory state and elevated insulin levels in diabetes may promote cancer cell growth 1.

From the Research

Relationship Between Diabetes Mellitus and Pancreatic Cancer

• The relationship between Diabetes Mellitus (DM) and pancreatic cancer is complex, with diabetes being both a risk factor for pancreatic cancer and a potential result of the disease 2, 3.
• Studies have shown that diabetes can increase the risk of pancreatic cancer, with a causal relationship between the two diseases well established 4, 5.
• The risk of pancreatic cancer is higher in patients with poorly controlled diabetes, with a study finding a hazard ratio of 3.61 for pancreatic cancer in diabetic patients with poor glycemic control 6.
• Metformin treatment has been shown to reduce the risk of pancreatic cancer and improve survival in diabetic patients with pancreatic cancer, primarily by decreasing insulin/IGF signaling and inhibiting the mTOR pathway 2, 4.
• Biomarkers for early diagnosis of pancreatic cancer among diabetic patients are being researched, with the goal of identifying patients at high risk of developing pancreatic cancer 3.

Risk Factors and Treatment

• Risk factors for pancreatic cancer include smoking, obesity, heavy alcohol consumption, and chronic pancreatitis 2, 3.
• Metformin has been shown to have anti-tumorigenic effects, including downregulating specificity protein transcription factors and associated genes, altering microRNAs, decreasing cancer stem cell proliferation, and reducing DNA damage and inflammation 2.
• Treatment of pancreatic cancer often involves palliative chemotherapy, with metformin treatment associated with longer overall survival in patients with advanced pancreatic cancer 4.

Diabetes and Pancreatic Cancer Association

• The association between diabetes and pancreatic cancer is strong, but often misunderstood, with long-standing type 1 and type 2 diabetes increasing the risk of pancreatic cancer 5.
• Type 3c diabetes, also known as pancreatogenic diabetes, is a common condition that can be induced by pancreatic cancer, and strategies to differentiate it from type 2 diabetes are being developed 5.
• Reversing obesity and hyperinsulinemia, achieving good glycemic control in diabetic patients, and identifying patients with pancreatogenic diabetes at an early stage may help reduce the risk of pancreatic cancer 5.