Recent-Onset Diabetes, Weight Loss Tied to Cancer in 30-Year Study

Individuals with recent-onset diabetes accompanied by weight loss had a high risk for pancreatic cancer and could be a group that would benefit from surveillance, scientists said.

In a cohort of 159,025 individuals followed for 30 years, those with recent-onset diabetes and weight loss of 1-8 lbs had more than three times the risk for pancreatic cancer (HR 3.61, 95% CI 2.14-6.10) compared with those without diabetes or weight loss, reported Chen Yuan, ScD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, and colleagues.

As shown in their study online in JAMA Oncology, individuals with recent-onset diabetes who lost more than 8 lbs had close to seven times the risk (HR 6.75, 95% CI 4.55-10.0). These associations were even stronger in those who were older, had a healthy body weight, and who had not intended to lose weight.

More than 80% of patients diagnosed with pancreatic cancer have advanced, incurable disease. However, patients who are diagnosed early can be cured with aggressive treatment. Screening of the general population, however, is not recommended by current guidelines. Therefore, identifying high-risk groups for whom the risk-to-benefit ratio would be favorable is important, Yuan and colleagues said.

"The identified risks in this population were similar to those for families with a history of pancreatic cancer and inherited genetic mutations in pancreatic cancer predisposition genes," the researchers wrote. "Members of such families undergo pancreatic cancer surveillance after age 50 to 55 at specialized clinics, and data indicate a shift to earlier-stage disease diagnosis and longer patient survival with surveillance."

Whether or not individuals with recent-onset diabetes and weight loss should be screened is a question to be explored in a clinical trial, Yuan and co-authors said. "Nevertheless, the coexistence of these symptoms should be recognized by clinicians given that both the relative and absolute risks for pancreatic cancer are high, particularly in individuals with healthy weight before weight loss or those who are not trying to lose weight through changes in physical activity or diet."

Asked for his opinion, Peter Campbell, PhD, scientific director of epidemiology research at the American Cancer Society in Atlanta, said the study was consistent with several previous well-conducted studies showing that diabetes, especially recent-onset diabetes, and unintentional weight loss are potential signs of an impending pancreatic cancer diagnosis.

"The more novel finding here is that when both risk factors are combined, the risk is even greater," Campbell, who was not involved in the study, said in an email to MedPage Today.

"While this finding isn't surprising, it underscores the importance of clinicians being aware of the relevance of these two risk factors in combination. In the future, it'll be important to see if this combined risk factor would be useful to determine whether some patients might be appropriate candidates for additional follow-up work for a pancreatic cancer diagnosis."

The study included 112,818 female participants from the Nurses' Health Study (NHS) and 46,207 men from the Health Professionals Follow-Up Study (HPFS). Mean age was 59.4 for the women and 64.7 for the men. Individuals with a history of diabetes or cancer at baseline were not included. Body weight and health status were self-reported at baseline and subsequently every other year via questionnaires.

Recent-onset diabetes was defined as a diagnosis within 4 years. Baseline was set at 1978 for the NHS and 1988 for the HPFS. Overall, the study included 4.5 million person-years of follow-up. There were 1,116 incident cases of pancreatic cancer during the study period.

The investigators found that new-onset diabetes and weight loss were associated with pancreatic cancer risk separately, although the associations were not as strong. Compared with participants with no diabetes, those with recent-onset diabetes had an age-adjusted hazard ratio (HR) for pancreatic cancer of 2.97 (95% CI 2.31-3.82), and those with long-standing diabetes had an HR of 2.16 (95% CI 1.78-2.60).

Compared with those with no weight loss, participants who reported a weight loss of 1-4 lbs had an HR for pancreatic cancer of 1.25 (95% CI 1.03-1.52). Those who lost 5-8 lbs had an HR of 1.33 (95% CI 1.06-1.66), and those with more than an 8 lb weight loss had an HR of 1.92 (95% CI, 1.58-2.32).

In addition, among participants with recent-onset diabetes and weight loss, the study found particularly high incidence rates of pancreatic cancer in those age 70 or older (234 incident cases per 100,000 person-years), those with a body-mass index of less than 25 before weight loss (400 incident cases per 100,000 person-years), and those with a low likelihood of intentional weight loss judging by changes in physical activity and diet (334 incident cases per 100,000 person-years). Hazard ratios and 95% confidence intervals were not presented for these groups, however.

Study limitations, the authors said, included that the biennial questionnaires could have missed some cases of pancreatic cancer with recent-onset diabetes, as some patients may have developed diabetes after the last questionnaire was returned. In addition, study participants were predominantly white healthcare professionals, and so the results might not be generalizable to a wider population.

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