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Overweight, High C-Peptide Predicts Future Mortality From Prostate Cancer

Both excess body weight and a high plasma concentration of C-peptide predispose men with a subsequent diagnosis of prostate cancer to an increased likelihood of dying of the disease, according to the results of a long-term survival analysis.

"Excess body-mass index (BMI) has been associated with adverse outcomes in prostate cancer, and hyperinsulinaemia is a candidate mediator, but prospective data are sparse," write Jing Ma, PhD, from Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, and colleagues. "We assessed the effect of prediagnostic BMI and plasma C-peptide concentration (reflecting insulin secretion) on prostate cancer-specific mortality after diagnosis."
This analysis was of men who were diagnosed with prostate cancer during the 24 years of follow-up in the Physicians’ Health Study. For 2546 men in whom prostate cancer developed, BMI measurements were available at baseline in 1982 and 8 years later in 1990. In addition, 827 men had baseline measurements of C-peptide concentration.

The risk for prostate cancer–specific mortality associated with BMI and C-peptide concentration was determined with Cox proportional hazards regression models controlling for age, smoking, time between BMI measurement and prostate cancer diagnosis, and competing causes of death. Overweight was defined as a BMI of 25.0 to 29.9 kg/m2 and obesity as a BMI of 30 kg/m2 or more.

Of 2546 men diagnosed with prostate cancer during follow-up, 989 (38.8%) were overweight and 87 (3.4%) were obese. During follow-up, 281 men (11%) died of prostate cancer. The risk for mortality from prostate cancer was significantly higher in overweight men and obese men vs men of healthy weight at baseline (proportional hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.16 – 1.88 for overweight men and 2.66; 95% CI, 1.62 – 4.39 for obese men; P for trend < .0001).

After controlling for clinical stage and Gleason grade, the trend remained significant. The trend was stronger for prostate cancer diagnosed during the prostate-specific antigen (PSA) screening era (1991-2007) vs during the pre-PSA screening era (1982-1990), or when using BMI measurements from 1990 vs those obtained from 1982.

Of the 827 men for whom baseline C-peptide concentration data were available, 117 (14%) died of prostate cancer. Compared with men in the lowest quartile (low) of C-peptide concentrations, those in the highest quartile (high) had a higher risk for prostate cancer mortality (HR, 2.38; 95% CI, 1.31 – 4.30; P for trend = .008). Compared with men of normal weight at baseline and low C-peptide concentrations, those with overweight or obesity at baseline and high C-peptide concentrations had a 4-fold greater risk for mortality (HR, 4.12; 95% CI, 1.97 – 8.61; P for interaction = .001), independent of clinical predictors.
"Excess bodyweight and a high plasma concentration of C-peptide both predispose men with a subsequent diagnosis of prostate cancer to an increased likelihood of dying of their disease," the study authors write. "Patients with both factors have the worst outcome. Further studies are now needed to confirm these findings."

Limitations of this study include lack of detailed information about PSA screening and cancer treatment; only one C-peptide measurement at baseline, years before prostate cancer diagnosis; and participants not a representative sample of patients with prostate cancer in the general population.
"Our data suggest that the recent progress in prostate cancer control might have been attenuated by the increased prevalence of obesity and hyperinsulinaemia," the study authors conclude. "It also adds to the rationale for investigation of new therapeutic and prevention strategies, such as use of insulin-lowering or antidiabetic drugs, and new agents that target the insulin/insulin-like growth factor-1 receptor family as an adjuvant therapy for prostate cancer."
Practice Pearls:

  • Higher BMI may promote lower serum levels of PSA, but obesity does not appear to independently promote prostate cancer in most research. Nonetheless, higher BMI has been associated with more aggressive prostate tumors and can predict a higher rate of treatment failure for prostate cancer.
  • The current study suggests that both overweight or obesity and elevated C-peptide levels increase the risk for mortality from prostate cancer.

Lancet Oncol. Published online October 6, 2008.

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