Pd29-01 Does Insulin Resistance Predict Aggressive Prostate Cancer? Results From the Reduction by Dutasteride of Prostate Cancer (Reduce) Trial

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You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History I (PD29)1 May 2024PD29-01 DOES INSULIN RESISTANCE PREDICT AGGRESSIVE PROSTATE CANCER? RESULTS FROM THE REDUCTION BY DUTASTERIDE OF PROSTATE CANCER (REDUCE) TRIAL Renning Zheng, James P. Daniels, Daniel Moreira, and Stephen J. Freedland Renning ZhengRenning Zheng , James P. DanielsJames P. Daniels , Daniel MoreiraDaniel Moreira , and Stephen J. FreedlandStephen J. Freedland View All Author Informationhttps://doi.org/10.1097/01.JU.0001008736.23117.7f.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Some studies suggest that higher insulin and insulin resistance are risk factors for prostate cancer (PC). However, not all studies agree. We examined the association between insulin and insulin resistance and risk of low- and high-grade prostate cancer in the REDUCE trail. METHODS: REDUCE was a 4-year randomized trial of dutasteride vs. placebo for PC prevention. All men had a pre-study negative biopsy and an elevated PSA. Patients underwent a study mandated biopsy at 2- and 4-years. Fasting insulin and glucose levels were measured at study baseline. Using these values, we calculated the Homeostatic Assessment of Insulin Resistance (HOMA-IR). Multivariable logistic regression was used to test the association between insulin level and insulin resistance and PC risk. To assess associations with tumor grade (low-grade – grade group 1; high-grade – grade group 2-5), we used a multinominal regression. Results were adjusted for age, PSA, prostate volume (log-transformed), DRE, treatment, race and smoking. Subgroup analyses were further conducted by diabetes (yes/no). To alleviate the effect of extreme value, we excluded patients with outlier values for insulin defined as greater the 1.5 times the interquartile range (IQR) above the 3rd quartile. RESULTS: Of 5594 men with complete covariate data, 5221 remained after excluding outliers. Both hyperinsulinemia and higher HOMA-IR were unrelated to overall PC risk. However, when stratified by grade, higher insulin (p=0.048) and higher HOMA-IR (p=0.039) were correlated with lower risk of low-grade PC but higher risk of high-grade PC, though only the association between HOMA-IR was statistically significant (p=0.024). When stratified by diabetes status, there were either significant or suggestive interactions between both insulin and HOMA-IR by diabetes for predicting overall PC (p≤0.035), low-grade PC (p≤0.15), and high-grade PC (p≤0.072). In general, among diabetic patients, insulin and HOMA-IR were unrelated to overall PC or low-grade, but both were significantly linked with increased risk of high-grade PC (p≤0.035). In contrast, among non-diabetic patients, both insulin and HOMA-IR were only linked with lower-risk of low-grade PC and not with overall PC or high-grade PC. CONCLUSIONS: Hyperinsulinemia and insulin resistance were associated with decreased risk of low-grade PC in non-diabetes subjects, and increased risk of high-grade PC in diabetes patients. These data support the idea that insulin may be a driver of aggressive PC in diabetic patients. Source of Funding: Dr. James Daniels is funded by the NIH grants TL1 DK132768 and U2C DK129496 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e618 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Renning Zheng More articles by this author James P. Daniels More articles by this author Daniel Moreira More articles by this author Stephen J. Freedland More articles by this author Expand All Advertisement PDF downloadLoading ...