New links found between Type 2 diabetes and pancreatic cancer

Type 2 diabetes (T2D) is a major risk factor for several cancers, including pancreatic cancer. Epidemiological studies have shown that patients with T2D are 1.8 times more likely to develop pancreatic cancer, and that when patients are diagnosed with pancreatic cancer, they present with diabetes in 40%-to-60% of cases.Until now, little was known about the functional interactions between T2D and the pancreas. However, French researchers from INSERM (Institut national de la santé et de la recherche médicale) and other health centres in France, have now discovered one of the mechanisms by conducting the first epigenetic study of the impact of T2DM on the pancreas as a whole.T2D-induced epigenetic changesTheir work, published in the journal Diabetes, reveals a robust association between T2D and hypermethylation of the PNLIPRP1 gene, which alters its activity downwards. According to the scientists, this gene, which is involved in lipid metabolism within the exocrine pancreas (the part of the pancreas that secretes digestive enzymes), is “a strong candidate for T2D-induced epigenetic changes, leading to deleterious events, particularly in acinar cell cholesterol metabolism.” In other words, this modification of the PNLIPRP1 gene is linked to the hyperglycemia and subsequent hyperlipidemia of T2D, “and leads to cellular changes in the exocrine pancreas typical of precancerous states,” stated an INSERM press release.The study also revealed that rare or frequent mutations in the PNLIPRP1 gene are associated with abnormalities in glycemic control, demonstrating the role of the exocrine pancreas, and not just the endocrine (insulin-secreting part of the pancreas), in the development of T2D. “Overall, the PNLIPRP1 gene and lipid metabolism appear to have a key role in a vicious circle linking diabetes, pancreatic cancer and the exocrine pancreas.”High mortalityAccording to the Canadian Cancer Society (CCS), pancreatic cancer will be the third leading cause of cancer death by 2024, and an estimated 6,100 Canadians could die from it, a higher number than deaths from breast or prostate cancer. Over the past 35 years, the mortality rate for pancreatic cancer has remained virtually unchanged, according to the CCS, pointing out that this is largely due to the fact that pancreatic cancer is often detected at an advanced stage. As a result, net survival five years after diagnosis is 10% in Canada.In their conclusions, the French researchers said that, “In vitro and in vivo models showed that statins delayed the formation of ductal adenocarcinoma (the most common pancreatic cancer tumour) in mutant mice.” They added that these results are confirmed by human studies, in which statin use led to a significant reduction in pancreatic cancer risk and improved patient survival. Thus, they suggested that statins could interrupt the process causing hypermethylation of the PNLIPRP1 gene and thus protect patients against pancreatic cancer “particularly when administered early and before the development of the disease.”This article was translated from its original French and first appeared on our sister site Profession Santé.

New links found between Type 2 diabetes and pancreatic cancer

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