SAN DIEGO—Use of prandial insulin (ie, insulin given at mealtimes) appears to be linked to cancer risk, according to a substudy of the large randomized Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial presented at the 71st Scientific Sessions of the American Diabetes Association. Other factors associated with development of cancer in this substudy included increasing body mass index (BMI), older age, and smoking.
“Insulin exposure has been proposed as a possible risk factor for the increased risk of cancer in patients with type 2 diabetes. Although we found no association with insulin, basal insulin, or insulin glargine, there was an association with use of prandial insulin. This is hypothesis-generating and needs to be studied further,” stated presenting author Marwan Hamaty, MD, an endocrinologist at the Cleveland Clinic in Ohio.
ACCORD was a large randomized, double 2 × 2 factorial designed trial of 10,251 patients with type 2 diabetes. All patients were randomized to receive either intensive or standard glycemic therapy. Those with moderate levels of dyslipidemia (n = 5518) were further randomized to either intensive or standard lipid-lowering therapy. The remaining 4733 patients were randomized to achieve intensive or standard blood pressure targets. The substudy presented focused on the glycemia therapy arm; 5076 patients were randomized to intensive glycemia control and 5070 to standard glycemia control.
Among these patients, there were 304 cancer events: hospitalization for cancer but no deaths in 101 patients and cancer-related deaths in 203. The incidence of cancer was not affected by gender, but as would be expected, was higher in cigarette and tobacco smokers and lower in never-smokers. Also, cancer incidence was higher in patients older than 70 years, and in patients with increased BMI. No association was found between alcohol use and insulin use at baseline.
Increasing hemoglobin A1c was associated with risk of cancer. “For every 1% increase in A1c, cancer risk increased by 30%, even after adjustment for the glycemia intervention,” Hamaty told listeners.
After adjusting for a number of covariates (baseline age, sex, BMI, insulin use, tobacco use, alcohol use, history of cardiovascular events, as - signment to glycemia treatment group, intensive versus standard blood pressure, and lipid lowering), a significant association was found between prandial insulin and cancer risk, with a hazard ratio (HR) of 2.30 (95% confidence interval [CI], 1.08-4.90; P = .03).
This association remained significant even after correction for basal insulin exposure (HR, 2.41 [95% CI, 1.05-5.49]; P = .03). The study had several limitations, Hamaty noted. It was a post-hoc analysis, not a prespecified one, and there were a relatively small number of cancer- related events. Also, the use of concomitant medications was not accounted for and might have influenced results. Nevertheless, these findings suggest that further study is needed, he said.