Poor glycemic control linked to prostate cancer progression
medwireNews: In men with prostate cancer and diabetes, higher glycated hemoglobin (HbA1c) levels are associated with an increased risk for developing metastases and castration-resistant disease, findings indicate.
“Because HbA1c is a good marker of glycemic control, these data suggest serum glucose levels may significantly influence [prostate cancer] progression and long-term clinical outcomes,” write Stephen Freedland (Cedars-Sinai Medical Center, Los Angeles, California, USA) and co-authors in Cancer.
“If validated in larger studies with longer follow-up, the results of the current study would support clinical trials to test whether better glycemic control can improve long-term clinical outcomes in men undergoing [radical prostatectomy],” they continue.
The analysis drew on the SEARCH (Shared Equal Access Regional Cancer Hospital) database to identify 1409 men with HbA1c values available within a year of having surgery at one of eight US centers between 2000 and 2017. Of these, 49.6% had an HbA1c value below 6.5%, 44.8% had an HbA1c value of 6.5–7.9%, and 5.6% had an HbA1c of at least 8.0%, indicating well, moderately, and poorly controlled diabetes, respectively.
Over a median follow-up of 6.8 years from the surgical procedure, there was no significant difference between the HbA1c subgroups with regard to biochemical recurrence.
But when treated as a continuous variable, higher HbA1c levels were associated with a significantly higher risk for metastases and castration-resistant prostate cancer (CRPC), with respective hazard ratios of 1.21 and 1.27 after adjusting for biopsy grade and prostate-specific antigen.
As a categorical variable, there were trends for an association between higher HbA1c categories and an increased risk for metastases and CRPC, but these did not reach statistical significance.
Similarly, the risk for prostate cancer-specific and all-cause mortality tended to be greater with higher HbA1c levels, but these relationships were not significant.
Speculating about the underlying causal mechanisms, the study authors write: “Because HbA1c is a surrogate marker of insulin resistance, it is possible that the impact of poor glycemic control on [prostate cancer] progression is due to the higher circulating insulin levels required to counter insulin resistance in those with long-standing hyperglycemia, and not the excess glucose itself.
“An alternative explanation may be that higher circulating glucose levels may be a marker of other processes, such as metabolic syndrome or a lack of physical activity, both of which have been shown to be correlated with poor clinical outcomes in some studies.”
They conclude, however, that “the causal mechanisms underlying these findings require further study.”
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