New research shows that patients with type 2 diabetes may experience a substantially higher rate of cancer mortality than the general population—by 18% for all cancers combined, 9% for breast cancer, and as much as 2.4-fold for colorectal cancer—according to a new study published by Ling et al in Diabetologia. Researchers also found that the rate of cancer mortality among patients with type 2 diabetes was around double the rate among the general population for diabetes-related cancers—including hepatic and pancreatic cancers for both male and female patients, as well as endometrial cancers for female patients.

Background

Accumulating epidemiologic evidence has shown that patients with type 2 diabetes may have a higher risk of incidence and mortality for some types of cancers as a result of prolonged exposure to the effects of increased blood sugar and insulin levels—insulin resistance and chronic inflammation being the potential underlying biological mechanisms. Robust evidence indicates that there is a causal relationship between type 2 diabetes and pancreatic, liver, and endometrial cancers. While previous studies have extensively investigated inequalities in cardiovascular outcomes among patients with type 2 diabetes, less is known about whether such inequalities exist for cancer mortality rates.

Study Methods and Results

In the new study—spanning from January 1, 1998 to November 30, 2018—researchers estimated standardized mortality ratios comparing mortality rates with the general population; and analyzed trends in all-cause, all-cancer, and cancer-specific mortality rates using factors such as age, sex, obesity, ethnicity, socioeconomic status, and smoking status among 137,804 patients aged 35 years and older with newly diagnosed type 2 diabetes.

After a median follow-up of 8.4 years, the researchers found that all-cause mortality rates decreased at all ages. All-cancer mortality rates—with the exception of nonmelanoma skin cancers—also decreased by 1.4% per year for patients aged 55 years and 0.2% for patients aged 65 years, but increased by 1.2% per year for patients aged 75 years and 1.6% for patients aged 85 years.

The researchers highlighted that decreasing cardiovascular mortality rates observed among the older age groups—the result of successful cardiovascular prevention and treatment in the past few decades—demonstrated that individuals who live longer may have a greater chance of experiencing other conditions and dying from other causes, including cancer. However, diabetes screening, better management of diabetes and its complications, earlier cancer detection, and improved cancer treatments may have benefited younger patients with type 2 diabetes in the same way as they have for the general population.

“The prevention of cardiovascular disease has been, and is still considered, a priority in [patients] with diabetes. Our results challenge this view by showing that cancer may have overtaken cardiovascular disease as a leading cause of death in [patients] with type 2 diabetes. Cancer prevention strategies, therefore, deserve at least a similar level of attention as cardiovascular disease prevention—particularly in older [patients] and for some cancers such as [hepatic], colorectal, and pancreatic cancers,” explained the study authors.

Additionally, the researchers uncovered a higher average annual percentage change (AAPC) in cancer mortality among female patients—1.5% compared with 1.0% among male patients—although female patients had lower cancer mortality rates throughout the study period. Biological factors, health-seeking behaviors, and lifestyle factors such as smoking and obesity all differed between male and female patients, but each factor’s relative contributions to cancer mortality was unknown. The least deprived/wealthiest patient population also had a higher cancer mortality AAPC of 1.5% compared with 1.0% among the most deprived/poorest patient population—leading to a narrowing but persistent gap by socioeconomic status.

Other key findings included a higher cancer mortality AAPC of 5.8% for patients who were categorized as morbidly obese compared with under 1.0% for those in other weight categories. In addition, the study revealed a higher cancer mortality AAPC of 2.4% for patients who were White compared with a cancer mortality AAPC decline of 3.4% combined across patients who were not White.

Smokers also saw an increased cancer mortality AAPC of 3.4%, whereas for never-smokers, the cancer mortality AAPC fell by 1.4%. The researchers suggested that current health-care policies and structures could benefit never-smokers more than smokers—and that tailored interventions for smokers, such as specific screening programs, could help address increasing cancer mortality and all-cause mortality among smokers.

“Tailored interventions should also be considered for smokers, who had higher and steadily increasing cancer mortality rates. Interventions for smokers, in addition to stopping smoking could include campaigns to raise awareness of cancer and improve early detection. For [patients] with type 2 diabetes, early cancer detection through changes to existing screening programs, or more in-depth investigations for suspected/nonspecific cancer symptoms, may reduce the number of avoidable cancer deaths,” the study authors suggested.

Constant upward trends in mortality rates were also observed for patients with pancreatic, hepatic, and lung cancers at all ages; colorectal cancer at most ages; breast cancer at younger ages; and prostate and endometrial cancers at older ages.

Compared with the general population, patients with type 2 diabetes had a more than a 1.5-fold increased risk of colorectal, pancreatic, hepatic, and endometrial cancer mortality during the whole study period. Despite national reports from between 1998 and 2018 showing a decrease in breast cancer mortality among younger patients, the new study revealed an increasing breast cancer mortality rate of 4.1% per year among younger female patients with type 2 diabetes.

Conclusions

“From this perspective, our results suggest that it may be helpful to extend breast cancer screening to young [female patients] with type 2 diabetes. However, given the high cost and potentially longer exposure to screening procedures, cost-effectiveness analyses are required to define the appropriate time window and identify subgroups who may benefit more,” the study authors underscored, adding that there were currently trials investigating the extension of the existing breast cancer screening window from individuals aged 50 to 70 years to 47 to 73 years for the general population. In addition, individuals with a family history of breast cancer or specific gene mutations are currently offered screenings at a younger age, but no current guidelines specifically consider the increased risk of breast cancer among female patients with type 2 diabetes.

The study authors concluded, “[O]ur findings underline the growing cancer burden in [patients] with type 2 diabetes, particularly in older individuals, and highlight the need to prioritize cancer prevention, research, and early detection and management in this population—especially for [patients with] colorectal, pancreatic, [hepatic], and endometrial cancers, whose mortality rates were substantially higher in individuals with type 2 diabetes than in the general population.”

Disclosure: For full disclosures of the study authors, visit link.springer.com.