Clinical Investigation
Type of Diabetes Mellitus and the Odds of Gleason Score 8 to 10 Prostate Cancer

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Purpose

It has been recently shown that diabetes mellitus (DM) is significantly associated with the likelihood of presenting with high-grade prostate cancer (PCa) or Gleason score (GS) 8 to 10; however, whether this association holds for both Type 1 and 2 DM is unknown. In this study we evaluated whether DM Type 1, 2, or both are associated with high-grade PCa after adjusting for known predictors of high-grade disease.

Methods and Materials

Between 1991 and 2010, a total of 15,330 men diagnosed with PCa and treated with radiation therapy were analyzed. A polychotomous logistic regression analysis was performed to evaluate whether Type 1 or 2 DM was associated with odds of GS 7 or GS 8 to 10 compared with 6 or lower PCa, adjusting for African American race, age, prostate-specific antigen (PSA) level, and digital rectal examination findings.

Results

Men with Type 1 DM (adjusted odds ratio [AOR], 2.05; 95% confidence interval [CI], 1.28–3.27; p = 0.003) or Type 2 DM (AOR, 1.58; 95% CI, 1.26–1.99; p < 0.001) were significantly more likely to be diagnosed with GS 8 to 10 PCa compared with nondiabetic men. However this was not true for GS 7, for which these respective results were AOR, 1.30; 95% CI, 0.93–1.82; p = 0.12 and AOR, 1.13; 95% CI, 0.98–1.32; p = 0.10.

Conclusion

Type 1 and 2 DM were associated with a higher odds of being diagnosed with Gleason score 8 to 10 but not 7 PCa. Pending validation, men who are diagnosed with Type I DM with GS 7 or lower should be considered for additional workup to rule out occult high-grade disease.

Introduction

Prostate cancer (PCa) is the most common noncutaneous malignancy among men in the US and second leading cause of cancer death. One in 6 men will be diagnosed with PCa during the course of their lifetime(1). Known risk factors for PCa development include higher prostate-specific antigen (PSA), family history, abnormal digital rectal examination (DRE) result, increasing age, and African American race(2).

Recent data have disclosed diabetes mellitus (DM) to also be a significant risk factor, independent of race, associated with the occurrence of high-grade or Gleason score (GS) 8 to 10 PCa, but not GS 7 PCa, when compared with GS 6 or lower(3). Published reports demonstrate increased risk of all-cause mortality in cancer patients with pre-existing DM, compared with those without. Explanations for worse outcome include increased proliferation of tumor cells triggered by higher concentration of insulin-like growth factors and hyperglycemia(4). Moreover, recent observational studies have also shown a link between long-term use of exogenous insulin and increased cancer risk(5).

However, it remains unknown whether the increased risk of GS 8 to 10 PCa in men with DM is specific to DM Type I, 2, or both. This is particularly relevant because the onset of DM Type 1 is typically during adolescence(6) and much earlier than DM Type 2, which typically presents when men are in their fifth decade(7). The earlier onset of DM Type 1, if associated with an earlier age at PCa diagnosis, raises the question of whether men with DM Type 1 could benefit from earlier prostate cancer screening. Also, if DM Type 1 is associated with increased risk of GS 8 to 10, consideration to additional workup should be made in men who are diagnosed with Type I DM that is GS 7 or lower, to rule out occult high-grade disease. Therefore, the purpose of this study was to evaluate whether DM Type 1, 2, or both are associated with GS 8 to 10 disease after adjusting for known predictors of high-grade PCa.

Section snippets

Patient population

The study evaluated 15,330 men who were diagnosed with Gleason 6 or lower (n = 10,112), Gleason 7 (n = 4,120) and Gleason 8 to 10 (n = 1,098) PCa at either the Chicago Prostate Cancer Center (n = 8,105), in one of 20 community-based medical centers within the 21st Century Oncology practice (n = 7,019), located in the states of Florida, New York, and North Carolina, or at one of three academic institutions in Boston (n = 206) (Dana Farber Cancer Institute, Brigham and Women's Hospital,

Results

Distribution and comparison of patient and tumor characteristics stratified by presence or absence of DM, and type of DM when present.

As shown in Table 1, of all 15,330 men, 1,202 had DM, of whom 15% (184) had Type 1 and 85% (1,018) had Type 2. Men with Type 1 or Type 2 DM were significantly more likely (p ≤ 0.01) to be AA compared with men without DM, with the distribution being 10% or 11% compared with 5%, respectively. The median PSA was significantly higher among men with DM Type 1 compared

Discussion

It has recently been shown that DM is significantly associated with an increased odds of presenting with GS 8 to 10, compared with GS 6 or lower, PCa.3, 11 In this study, we found that both Type 1 and 2 DM were associated with increased risk of GS 8 to 10 PCa, but not GS 7 PCa compared with GS 6 or lower. To our knowledge, this is the first time that the impact of the type of DM on high-grade PCa has been studied. The clinical significance of these results is that for men with Type I or II DM

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    Conflict of interest: none.

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