T2D, Weight Loss Independently Linked to Higher Pancreatic Cancer Risk

Individuals with recent-onset type 2 diabetes (T2D) accompanied by weight loss have a high risk for developing pancreatic cancer, according to a study published in JAMA Oncology. The finding potentially makes this population a group that can benefit from early detection strategies.

Pancreatic cancer has a 5-year survival rate of less than 10% which is largely associated with the diagnosis occurring at an advanced stage when the cancer is no longer curable. As such, pancreatic cancer is the third-leading cause of cancer-related death in the United States.

“To date, patients with a strong family history or genetic predisposition and those with pancreatic cystic lesions have been the primary focus of pancreatic cancer early detection programs, with initial evidence indicating a shift to earlier stage disease and longer survival among those who undergo surveillance imaging,” authors wrote. However, this population only represents 15 to 20% of individuals with the cancer, making identification of other high-risk groups necessary to enhance screening efforts.

Although T2D has been identified as a risk factor for pancreatic cancer, a subset of patients with the cancer develop diabetes several months to years before their cancer diagnosis.

To evaluate the association of T2D and recent weight change with subsequent risk of pancreatic cancer in the general population, researchers analyzed data from 112,818 women and 46,207 men enrolled in the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS).

The NHS began in 1976 and initially enrolled 121,700 US female nurses aged between 30 and 55 years. Similarly, the HPFS was initiated in 1986 and recruited 51,529 US male health professionals between the ages 40 and 75. “Since enrollment, participants in both the NHS and HPFS have updated their information through biennial follow-up questionnaires,” researchers said.

For the current study, baseline was set at 1978 for the NHA and 1988 for the HPFS. All participants with prevalent diabetes or prior history of cancer at baseline were excluded.

Mean age (SD) of female participants was 59.4 (11.7) years while mean male age was 64.7 (10.8) years. During the 4.5 million person-years of follow-up 1116 (0.7%) incident cases of pancreatic cancer were identified (incident rate of 25 per 100,000 person-years).

Analyses found:

• Compared with participants with no diabetes, those with recent-onset T2D 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 age-adjusted HR of 2.16 (95% CI, 1.78-2.60)
• Compared with those with no weight loss, participants who reported a 1- to 4-lb weight loss had an age-adjusted HR for pancreatic cancer of 1.25 (95% CI, 1.03-1.52), those with a 5- to 8-lb weight loss had an age-adjusted HR of 1.33 (95% CI, 1.06-1.66), and those with more than an 8-lb weight loss had an age-adjusted HR of 1.92 (95% CI, 1.58-2.32)
• Participants with recent-onset T2D accompanied by weight loss of 1 to 8 lb (91 incident cases per 100,000 person-years [95% CI, 55-151]; HR, 3.61 [95% CI, 2.14-6.10]) or more than 8 lb (164 incident cases per 100 000 person-years [95% CI, 114-238]; HR, 6.75 [95% CI, 4.55-10.00]) had a substantially increased risk for pancreatic cancer compared with those with neither exposure (16 incident cases per 100,000 person-years; 95% CI, 14-17)

In addition, “incidence rates were even higher among participants with recent-onset diabetes and weight loss with a body mass index of less than 25 before weight loss (400 incident cases per 100,000 person-years) or whose weight loss was not intentional judging from increased physical activity or healthier dietary choices (334 incident cases per 100,000 person-years),” researchers said.

Although the US Prevention Services Task force does not recommend screening for pancreatic cancer in individuals who are asymptomatic and have only an average risk of developing the cancer, the current study found the co-occurrence of weight loss with recent-onset diabetes increases the risk of pancreatic cancer by more than 6-fold. “Identification and characterization of high-risk groups can potentially limit surveillance to individuals for whom the risk-to-benefit ratio of screening would be most favorable,” authors argued.

The HRs identified in this study are also similar to those in families with a history of pancreatic cancer and inherited genetic mutations in pancreatic cancer predisposition genes, members of whom undergo cancer surveillance after age 50 to 55 years. Because of this, large prospective studies ought to be carried out to determine whether recent-onset diabetes after age 50, in the context of weight loss, should trigger pancreatic cancer surveillance, researchers noted.

Use of a biennial questionnaire could have resulted in a lower proportion of participants with pancreatic cancer who were identified with recent-onset diabetes given that some patients may have developed diabetes after the questionnaire was returned, marking a limitation to the study. Researchers also could not determine whether weight loss had already begun before the development of hyperglycemia or occurred only afterward. As the majority of participants were predominately White health professionals, a study of additional patient populations is warranted, authors conclude.

Reference:

Yuan C, Babic A, Khalaf N, et al. Diabetes, weight change, and pancreatic cancer risk. JAMA Oncol. Published online August 13, 2020. doi:10.1001/jamaoncol.2020.2948