Prediabetes Associated with 15% Increased Risk of Cancer

According to a recent meta-analysis, prediabetes is associated with a significant increase in cancer risk that is independent of the effects of obesity [Diabetologica. 2014].

Yuli Huang, MD, PhD, First People's Hospital of Shunde, Foshan, China, and colleagues found that prediabetes was associated with a 15% increased risk for cancer overall, based on data from 16 prospective, cohort studies. The risk differed depending on the type of cancer. The risk was particularly increased for liver cancer and stomach or colorectal cancer.

A total of 891,426 participants from the 16 studies were included in the meta-analysis. Four of the studies were from Asia, 11 were from the United States and Europe, and 1 was from Africa.

More than 10 years ago, the American Diabetes Association (ADA) changed its definition of prediabetes to a fasting plasma glucose (FPG) concentration ranging from 5.6 mmol/L to 6.9 mmol/L; however, other organizations have maintained their definition at a higher level, as a FPG concentration between 6.1 mmol/L and 6.9 mmol/L.

The risks of site-specific cancer among individuals with prediabetes was highest for liver cancer (relative risk [RR], 2.01), followed by colorectal and stomach cancer (RR, 1.55 for both), endometrial cancer (RR, 1.6), and breast and pancreatic cancer (RR, 1.19 for both).

Prediabetes was not found to be associated with bronchus, lung, prostate, ovary, kidney, or bladder cancer.

The researchers found that the risks were increased even when a lower FPG value of 5.6 mmol/L to 6.9 mmol/L was used. The researchers noted that this reaffirms the importance of screening for prediabetes using the ADA criteria with a view to cancer prevention.

As the authors point out, obesity — in itself a key risk factor for diabetes — has also been linked to cancer.

The researchers also did a sensitivity analysis since obesity is a risk factor of diabetes that is also linked to cancer. The sensitivity analysis included only studies that adjusted for body mass index (BMI).

After controlling for BMI, “we found that the presence of prediabetes remained associated with an increased risk of cancer by 22%,” the researchers said. “So we believe that the increased risk of cancer in individuals with prediabetes is independent of obesity.”

Dr. Huang and colleagues suggest that chronic hyperglycemia and resulting states, including chronic oxidative stress and the accumulation of advanced glycated end products, may serve as carcinogens, increasing he association between prediabetes and cancer risk. In addition, increased insulin resistance characteristic of prediabetes increases insulin secretion, and increased insulin levels may promote the growth of cancer cells. Certain genetic mutations may also predispose individuals with prediabetes to an elevated cancer risk.

The researchers also noted that metformin is associated with an approximately 30% reduction in the lifetime risk of cancer in diabetic patients.—Kerri Fitzgerald