Background: Diabetes is associated with a decreased prostate cancer risk, and may increase prostate cancer mortality among men with the diagnosis. The association of diabetes or earlier hyperglycemic states (i.e. prediabetes) on the most clinically relevant outcome, prostate cancer mortality in men without the diagnosis at baseline, has not been well studied and whether associations are similar across race is unknown. Thus, we aimed to rigorously characterize the association of diabetes and hyperglycemia with prostate cancer mortality. We classified hyperglycemia with a combination of 3 blood biomarkers - fasting glucose, hemoglobin A1c (HbA1c), and glycated albumin (%GA), which capture complementary aspects of glycemia.

Methods: We conducted a prospective study of 5,276 cancer-free white and black men attending visit 2 (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) Study. Death from prostate cancer was ascertained from the underlying cause on death certificates. Follow-up began at visit 2 and ended at date of death or 12/31/2012, whichever came first. There were 69 prostate cancer deaths in 96,617 person-years. Men were categorized as having diagnosed diabetes or jointly categorized using clinical or research-based cut points of the 3 biomarkers: low (HbA1c <5.0% or %GA <11.0% or fasting glucose <3.1 mmol/L); normal on all 3 biomarkers (reference: 5.0 to <5.7%; 11.0 to <16.0%; and <5.6 mmol/L, respectively); and high on any 1; on any 2; or on all 3 biomarkers. We used Cox proportional hazards regression to estimate the relative hazards (HR) of prostate cancer death and 95% confidence intervals for the joint terms for glycemia and the term for diagnosed diabetes adjusting for age, education, BMI, waist circumference, smoking, and race*field center, overall and by race.

Results: Mean age was 57 years and mean BMI was 27.7 kg/m2; 81% were white. Compared to men who were normal on all 3 biomarkers of glycemia, greater than 2-fold increased risk of prostate cancer mortality was observed among men high on any 1 biomarker (HR: 3.66; 95% CI: 1.42 to 9.48), any 2 biomarkers (HR: 2.58; 95% CI: 0.92 to 7.22), all 3 biomarkers (HR: 4.8; 95% CI: 1.10 to 20.95), and among men with diagnosed diabetes (HR: 3.18; 95% CI 0.94 to 10.73). Men with low glycemia also had an elevated risk of prostate cancer mortality (HR: 2.98; 95% CI: 0.98 to 8.90). Associations were similar in white and black men.

Conclusions: Using 3 biomarkers that capture complementary aspects of glycemia and have different sensitivities to non-glycemic factors, men without diagnosed diabetes who have hyperglycemia have an increased risk of death from prostate cancer compared to men who have normal glycemia levels, independent of BMI and other factors. Our findings did not appear to be influenced by racial differences in hyperglycemia.

Support: NHLBI contracts, NCI grants, NPCR

Citation Format: Michael Marrone, Elizabeth Selvin, John Barber, Elizabeth Platz, Corinne Joshu. Glycemia is positively associated with prostate cancer mortality in white and black men without diabetes when better classifying hyper- and normoglycemia using 3 biomarkers<!–EndFragment–> [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-285. doi:10.1158/1538-7445.AM2017-LB-285