New-Onset Diabetes Plus Unintentional Weight Loss Emerging as an Important Clue In Earlier Detection

The lives of many patients with breast cancer, cervical cancer and colon cancer have been saved due to the incredible power of early detection programs.

A case in point is the colonoscopy, a screening test for colorectal cancer recommended for all individuals age 50 and over, or even earlier if you are in a high risk group. One large study found this screening tool reduced the risk of death by 61 percent. Early detection of any cancer generally results in more favorable outcomes. Yet, finding pancreatic cancer in its earliest stages remains elusive, which is why researchers across the globe are looking at ways to change that paradigm.

One new study may provide some answers and a new strategy for early pancreatic cancer detection in a broad range of asymptomatic people with no known family history or germline mutations associated with the disease. The nonprofit and patient advocacy group Pancreatic Cancer Action Network (PanCAN) invested $25 million in the Early Detection Initiative, which screens patients recently diagnosed with diabetes or high blood glucose for pancreatic cancer. The study is designed as a randomized controlled clinical trial, the so-called gold standard of research, explains Anirban Maitra, M.B.B.S., co-principal investigator. PanCAN is working with the National Cancer Institute (NCI) and a diverse team of researchers, clinicians, statisticians and diagnostic specialists. The goal is to find out whether imaging at the time of new-onset diabetes leads to earlier detection of pancreatic cancer. Earlier detection of pancreatic cancer can mean longer-term survival, potentially even a cure through surgical intervention, for patients. Blood samples will be added to a collection maintained by the NCI for analysis of future pancreatic cancer biomarkers, according to PanCAN.

“When designing this study, all of the right people were brought to the table at the right time, which is the very beginning of the entire process,” says Maitra, professor of Pathology and Translational Molecular Pathology at The University of Texas MD Anderson Cancer Center in Houston, Texas. “Leadership from the National Cancer Institute and other experts all bring different areas of expertise not only in pancreatic cancer, but also in developing a big trial like this. We took a lot of input from a lot of different people and tried to address as many concerns as possible, without making anything too bloated or too watered down. I’ve been involved in a lot of studies, and I have to say this study is very rigorous in its design. It is absolutely worth all of the effort.”

Developing an early detection strategy from scratch “for a cancer that even five years ago was considered hopeless, shows how much the entire field is moving forward,” Maitra notes. “Obviously, more needs to be done, but clearly early detection of pancreatic cancer is no longer a joke. It’s become part of the conversation, and I’m happy about that. It’s also reassuring to know that many diverse groups are coming to the same conclusion about new-onset diabetes.”

New-Onset Diabetes Connection

Much of the early research on the new-onset diabetes and pancreatic cancer connection is credited to Suresh Chari, M.D., currently professor, Department of Gastroenterology, Hepatology, and Nutrition at The University of Texas MD Anderson Cancer Center. Chari was a faculty member for about 20 years at the Mayo Clinic in Rochester, Minnesota. While there, he led Mayo’s Pancreas Interest Group and was Director of the Pancreas Clinic. Since 2003, his research, focused on pancreatic cancer in individuals with new-onset diabetes, has been funded by the National Institutes of Health. His team’s findings led the National Cancer Institute to make the study of pancreatic cancer and diabetes one of its top priorities.

“New-onset diabetes accompanied by weight loss is really a signal that pancreatic cancer may be the cause,” says Chari, who is the study chair on the Early Detection Initiative. “We’ve known about a diabetes and pancreatic cancer connection for about 130 years, but that association is very modest. Diabetes over age 50 is unfortunately very common, and it’s almost always associated with weight gain. But new-onset diabetes, less than 3 years in duration, along with weight loss and glucose levels that rise rather rapidly provide us a big clue that something is going on. And that something may be pancreatic cancer.”

Studies also show that new-onset diabetes often resolves after surgery to remove the pancreatic cancer. “About one-quarter of patients with pancreatic cancer are diagnosed with diabetes up to three years before the diagnosis of pancreatic cancer,” Chari explains, adding that those with new-onset diabetes over age 50 have about an eight-fold higher risk for having pancreatic cancer. Conversely, the risk of pancreatic cancer in those with long-standing diabetes, generally defined as more than three years, is only 1.5 to 2.0 times higher, which is not fully explained by shared risk factors between the two diseases, such as obesity.

“Developing a strategy to use new-onset diabetes as a kind of marker for early diagnosis of pancreatic cancer really depends on our ability to tell the difference between the common type 2 adult-onset diabetes and diabetes associated with pancreatic cancer,” says Chari. “What we learn from this study can potentially lay the groundwork to diagnose early-stage pancreatic cancer that’s asymptomatic.”

About the Study

In the U.S., about 2 million adults are diagnosed with new-onset diabetes every year. To get a large enough sample, the study will enroll up to 12,500 patients across the U.S., all of whom will be randomized to either an observational arm or interventional arm.

Participants in the intervention group will have blood screening, imaging tests, as well as a health survey. Participants in both arms will have passive follow-up using electronic medical records five years after enrollment in the study. Participants for the Early Detection Initiative will be identified through electronic medical record systems at participating institutions.

With the study’s focus on new-onset diabetes, a symptom that is often ignored when it comes to pancreatic cancer, as well as identifying a potential pool of pancreatic cancer cases that aren’t linked to genetic risk, both doctors agree that trial results could change clinical practice.

“This is a high-risk/high-reward study and its design really mitigates a lot of false positive and confounding errors where you find something spurious or an artifact,” Maitra says. “These safeguards are built into randomization and post-randomization, which is incredibly important. “This disease claims too many lives and is diagnosed way too late in the process. If we can detect it early and get the tumor out and prolong the survival we can start throwing out the other ‘c’ word. And that’s cure.”

Chari admits that he, too, is rather excited about the trial, especially after spending nearly two decades researching the new-onset diabetes connection to pancreatic cancer. “There was a time where some people thought maybe I was wasting my time,” Chari laughs. “But the world of science is ruled by those fundamental observations that are then translated into trials and then hopefully practice. I am not saying that new-onset diabetes is the only answer to early detection, but it could potentially be one of the answers for many more people.

“No matter what the results of this trial, we are going to get some incredibly solid information.”