Sudden onset of diabetes or rapid worsening of existing diabetes without clear causes such as weight gain or dietary changes may warrant suspicion of pancreatic cancer, according to a new study.
A joint research team led by professors Kang Shin-ae, Yoon Dong-sup, and Kim Hyung-sun of Gangnam Severance Hospital, Lee Min-young of Severance Hospital, and Park Joon-seong of Seoul National University Hospital announced Wednesday that they have identified for the first time the key molecular mechanism by which pancreatic cancer induces diabetes. The team found that the Wnt5a protein secreted by pancreatic cancer cells can reduce insulin secretion, causing hyperglycemia and diabetes.
The causal relationship between pancreatic cancer and diabetes has long been an unresolved puzzle in medicine. Clinically, it has been commonly observed that diabetes newly develops or existing diabetes symptoms sharply worsen before pancreatic cancer is diagnosed. However, there had been insufficient evidence to clearly determine whether hyperglycemia stemmed from insulin resistance or from functional defects in pancreatic beta cells, which secrete insulin.
The research team conducted oral glucose tolerance tests before and after surgery on 160 patients who underwent pancreatectomy at Gangnam Severance Hospital to evaluate glucose metabolism and insulin secretion function. The results showed that the 72 pancreatic cancer patients exhibited more severe hyperglycemia and significantly reduced insulin secretion before surgery compared with the control group of 88 non-pancreatic cancer patients. The pancreatic cancer group also showed more pronounced improvement in hyperglycemia after surgery, with a relatively smaller decrease in insulin secretion function. The team explained that this suggests factors secreted from pancreatic tumors before surgery had suppressed insulin secretion and affected blood glucose, and that tumor removal partially resolved these problems.
Analysis of patients' blood and pancreatic tissue revealed that concentrations of Wnt5a, a carcinogenic mediator protein, were abnormally high in the blood of pancreatic cancer patients. Expression of beta-catenin (β-catenin), a key component of the related signaling pathway, was also elevated in areas surrounding the pancreatic islets responsible for insulin secretion. In particular, concentrations of the Wnt5a protein in the blood tended to increase with greater beta-catenin expression in the pancreas and larger tumor size, and were closely associated with the severity of hyperglycemia and the degree of insulin deficiency.
"We now have grounds to suspect pancreatic cancer at an early stage in patients who suddenly develop diabetes without any specific cause," Professor Kang said. "The Wnt5a protein highlighted in this study has the potential to serve as an important biomarker for early detection of pancreatic cancer."
The findings were published in a recent issue of the international journal Experimental & Molecular Medicine.
