Prostate mortality higher for overweight men with high insulin secretion pre-diagnosis

Excess bodyweight and high plasma concentrations of C-peptide (a protein that reflects the amount of insulin secretion) in men who are subsequently diagnosed with prostate cancer are reliable indicators that they are more likely to die from their disease than those with lower levels, according to findings from a substudy of the Physician’s Health Study in an article published in the November edition of Lancet Oncology.

Several studies have suggested that men who are overweight, as measured by body-mass index (BMI), have an increased risk of prostate-cancer progression and disease-related death. However, long-term, prospective data on prostate cancer-specific mortality are scarce. Furthermore, although the high insulin concentrations associated with obesity could potentially explain the adverse effect of obesity on prostate cancer mortality, no studies have assessed the association between prediagnosic plasma concentrations of C-peptide—a marker of insulin secretion—and prostate cancer-specific mortality.

Therefore, Dr Jing Ma (Channing Laboratory, Department of Medicine, University of Harvard, Boston, MA) with Dr Michael Pollak (McGill University, Montreal, Canada) and colleagues assessed data from 2546 men diagnosed with prostate cancer during 24 years of follow-up in the Physician’s Health Study. The association between baseline BMI, baseline plasma C-peptide concentrations, and BMI measured at 8-years of follow-up and subsequent prostate cancer-related death was examined.

Men who were overweight (BMI 25–29•9 kg/m2) or obese (BMI ≥30 kg/m2) before diagnosis were significantly more likely to die from their prostate cancer than men of normal weight (BMI <25 kg/m2). This trend remained significant after controlling for clinical stage and Gleason grade. Baseline C-peptide concentrations were available for 827 men and those with the highest C-peptide plasma concentrations also had a higher risk of prostate-cancer mortality compared with men with the lowest concentrations. Men with both a high C-peptide concentration and high BMI prior to diagnosis of prostate cancer had a four times higher risk of disease-specific mortality, independent of other clinical predictors.

The findings provide “further impetus for men to avoid becoming overweight and to decrease their risk of metabolic syndrome by physical activity and diet...and also adds to the rationale for investigation of new therapeutics and prevention strategies such as use of insulin-lowering or antidiabetic drugs”, says Dr Ma.

Dr Pollak comments that it is remarkable that measurement of a blood hormone level, even prior to the diagnosis of a cancer, allows one to predict the behaviour of cancer that might arise many years in the future. He adds, “The adverse effect of a high insulin secretion rate (as reflected by high C-peptide levels) on prostate cancer mortality is greater in magnitude than the beneficial effect of chemotherapy currently used for advanced prostate cancer, and clearly points out the need for further research regarding the role of insulin and related hormones and metabolic factors in prostate cancer biology...while current practice assumes that androgens, such as testosterone, are the only hormones relevant to prostate cancer, our results suggest that other hormones may also play an important role, particularly in view of recent related research showing that prostate cancers have insulin receptors”.