Glycemic Status and Risk of Prostate Cancer

Abstract

Background: To examine the risk of prostate cancer and glucose tolerance in a large, racially diverse cohort. Methods: We conducted a cohort study of 47,209 male members of Kaiser Permanente Northern California who had completed at least one Multiphasic Health Checkup (MHC) between 1964 and 1973. The MHC provided information on diabetes, serum glucose 1 h after a 75-g oral glucose challenge test, demographics, and other health conditions. Cox proportional hazards were used to estimate relative risks (RR) while adjusting for confounders. Results: During a median follow-up of 18.4 years, a total of 2,833 men developed prostate cancer. At baseline, 4.6% (n = 2,159) of the cohort had diabetes and 33% had serum glucose of z200 mg/dL. After adjusting for age, race, birth year, and body mass index, RR (95% confidence interval) of prostate cancer

Diabetes and prostate cancer risk in the REDUCE trial

“…[25][26][27] Interestingly, several studies have reported increased PCa risk in the years immediately following diabetes onset but lower risk thereafter. 4,[8][9][10] This could be due to detection bias from more frequent health care encounters around the time of diagnosis or may reflect true biological disturbances. For instance, although type 2 diabetes leads eventually to hypoinsulinemia, insulin output actually increases during the initial phase of glucose intolerance.…”

“…4,[8][9][10] As time since diabetes onset was not available and because diabetes status was recorded at baseline, stratifying in this manner approximated diabetes progression as all men diagnosed with PCa in the latter half of REDUCE would have been diabetic for at least two and, more likely, 4 years given most PCa cases were detected on the 4-year biopsy. All statistical analysis was performed using Stata v11.2 (StataCorp, College Station, TX, USA).…”

“…Several studies reported decreased PCa risk among diabetics whereas others found either no protective effect or an elevated risk. [1][2][3][4][5][6][7][8][9][10][11][12] Two recent meta-analyses, one examining studies from 1971-2002 and the other extending this review to 2005, both concluded diabetes is inversely associated with PCa risk. 2,3 However, only a minor risk reduction (RR ¼ 0.91, 95% confidence interval (CI) 0.86-0.96) was noted in the first meta-analysis whereas, in the second, diabetes appeared protective only among studies conducted after widespread adoption of PSA screening (RR ¼ 0.73, 95% CI 0.64-0.83).…”

Diabetes Genes and Prostate Cancer in the Atherosclerosis Risk in Communities Study

“…A major limitation to consider when interpreting our results is the lack of information on stage and grade of PrCa, which prevented us from evaluating the T2D SNPs in association with PrCa aggressiveness. It will be important to evaluate these SNPs in association with PrCa aggressiveness in other studies since the T2D-PrCa association has previously been shown to differ by disease stage or grade in some (17, 19, 35–38), but not all studies (20, 39–40). Moreover, several of these T2D genes have been implicated in processes related to cell motility and migration, so it will be important to evaluate associations with advanced or metastatic disease.…”

Diabetes mellitus and risk of prostate cancer in the health professionals follow‐up study

“…The second meta-analysis included approximately twelve thousand additional prostate cancer cases 7–12 and the overall effect estimate of all relevant studies published through 2006 suggests an inverse association (HR: 0.84, 95% CI: 0.76, 0.93) 6. Additionally, in the past year several more studies examining this topic have also reported both significant and non-significant inverse relationships between DM and PCa 13–16. The biological basis for this inverse relationship may be routed in differential insulin, insulin-like growth factor-1, and/or bioavailable testosterone levels17 and if these two diseases are, in fact, inversely associated, this relationship may further our understanding of prostate cancer biology.…”