Predicting pancreatic cancer in patients with diabetes
Volume 8, Issue 2, June 2019
The UCP-1 gene may serve as a potential biomarker even before symptoms develop in high-risk groups.
Suresh T. Chari, M.D.
Mayo Clinic researchers have identified a gene called UCP-1 that could help predict the development of pancreatic cancer in people with type 2 diabetes. Their findings were published in the May 2019 issue of the journal Gastroenterology.
"Developing strategies for the early detection of pancreatic cancer in people without symptoms is critical for improving survival," said Suresh T. Chari, M.D., a gastroenterologist at Mayo Clinic in Rochester, Minnesota, and senior author of the published study.
For the study, Dr. Chari and his colleagues studied a group of patients with pancreatic cancer and monitored their fasting blood glucose, body weight and blood lipids during a five-year period before their diagnosis of pancreatic cancer. The researchers also reviewed serial CT scans completed over time for other indications before the cancer diagnosis.
The review of CT scans helped the researchers identify changes in patients' subcutaneous fat, visceral fat and muscle over time. The researchers found that metabolic changes, along with a rise in blood glucose, began in patients with pancreatic cancer 36 months before their cancer was diagnosed. The researchers also found that at 18 months before a pancreatic cancer diagnosis, patients experienced weight loss and a decrease in blood lipids, including triglycerides, total cholesterol and low-density cholesterol.
Dr. Chari said the decrease in fat and lipids 18 months before a pancreatic cancer diagnosis was similar to the effects of browning of white adipose tissue, a phenomenon found in other cancers. "Brown fat generates body heat, a phenomenon especially prominent in newborn babies but much less so in adults," he said.
A specific marker of brown fat is an uncoupling protein called UCP-1, Dr. Chari said. "White fat can be turned brown by turning on certain browning genes, including, UCP-1," he said. "We hypothesized that pancreatic cancer causes browning of subcutaneous fat, and we confirmed our hypothesis in animal and human studies."
The studies have important implications for the early detection of pancreatic cancer, Dr. Chari said. "Along with supporting data from animal and human studies, we were able to show that UCP-1 gene levels are markedly increased in patients with pancreatic cancer, compared with controls. We believe UCP-1 can potentially be used as a biomarker to predict pancreatic cancer in high-risk groups, such as patients with new-onset or long-standing type 2 diabetes who are unintentionally losing weight."