Diabetes in obese men with prostate cancer (PCa) increases their risk of metastasis after radical prostatectomy (RP), according to researchers.

A team led by Chenwei Wu, MD, and Stephen J. Freedland, MD, of the Duke Prostate Center at Duke University Medical Center in Durham, N.C., and the Durham VA Hospital, studied 2,058 U.S. veterans with PCa who were enrolled in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database and underwent RP.

For the cohort as a whole, diabetes at the time of RP was not associated with metastasis risk after adjusting for multiple variables, Drs. Wu and Freedland and colleagues reported online in BJU International. When the researchers divided men into obese and non-obese groups, however, they found that diabetes in obese patients was associated with a significant fourfold increased risk of metastasis, whereas diabetes in non-obese patients was not significantly associated with metastasis risk.

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Among obese men, diabetes was associated with a nonsignificant 39% increased likelihood of receiving aggressive secondary treatment (radiation or androgen deprivation therapy [ADT]). After excluding men who received adjuvant radiation or ADT, diabetes was associated with a significant 61% increased likelihood of receiving aggressive secondary treatment among obese men, suggesting that less aggressive secondary treatments could not explain the higher metastases risk.

Among the diabetics, longer diabetes duration was associated with higher metastasis risk. If this finding is confirmed in future studies, the researchers stated, “the clinical implication is that men with long-standing diabetes who develop PCa may harbor a more aggressive variant, and this possibility should be kept in mind when determining treatment.”

The study found that race had no significant effect on the association between diabetes and metastasis risk.

“Our findings add to the limited research on diabetes, obesity, and PCa progression, suggesting men with diabetes and obesity together might harbor particularly aggressive disease,” the authors concluded.

The new study also supports earlier findings from a study by Dr. Freedland and his colleagues linking diabetes to increased risk of biochemical recurrence after RP, but only in obese white men. According to the investigators, possible biological mechanisms for the new findings include changes in the hormonal milieu of obese men with diabetes, particularly decreased plasma concentrations of total and free testosterone, as well as elevated levels of insulin and insulin-like growth factor-I. All of these conditions have been shown in previous studies to be associated with increased PCa aggressiveness.