Diabetes and Prostate Cancer Outcomes in Obese and Nonobese Men After Radical Prostatectomy

Abstract

Background The link between diabetes and prostate cancer progression is poorly understood and complicated by obesity. We investigated associations between diabetes and prostate cancer-specific mortality (PCSM), castrate-resistant prostate cancer (CRPC), and metastases in obese and nonobese men undergoing radical prostatectomy (RP). Methods We included 4,688 men from SEARCH, a cohort of men undergoing RP from 1988 to 2017. Diabetes prior to RP, anthropometric and clinical data were abstracted from six Veterans Affairs Medical Centers electronic medical records. Primary and secondary outcomes were PCSM and metastases and CRPC, respectively. Multivariable-adjusted hazard ratios (adj-HRs) and 95% confidence intervals (CIs) were estimated for diabetes and PCSM, CRPC and metastases. Adj-HRs were also estimated in analyses stratified by obesity (BMI: nonobese <30 kg/m2; obese ≥30 kg/m2. All statistical tests were two-sided. Results Diabetes was not associated with PCSM (adj-HR=1.38; 95% CI = 0.86-2.24), CRPC (adj-HR=1.05; 95% CI = 0.67-1.64), or metastases (adj-HR=1.01; 95% CI = 0.70-1.46), among all men. Interaction terms for diabetes and obesity were statistically significant in multivariable models for PCSM, CRPC and metastases (P≤0.04). In stratified analyses, in obese men, diabetes was associated with PCSM (adj-HR=3.06; 95%CI = 1.40-6.69), CRPC (adj-HR=2.14; 95%CI = 1.11-4.15), and metastases (adj-HR=1.57; 95%CI = 0.88-2.78), though not statistically significant for metastases. In nonobese men, inverse associations were suggested for diabetes and prostate cancer outcomes without reaching statistical significance. Conclusions Diabetes was associated with increased risks of prostate cancer progression and mortality among obese, but not among nonobese men, highlighting the importance of aggressively curtailing the increasing prevalence of obesity in prostate cancer survivors.

Do Hispanic Puerto Rican men have worse outcomes after radical prostatectomy? Results from SEARCH

“…27 Moreover, obesity is a risk factor for diabetes, and our group recently observed obesity-related differences in the associations between diabetes and PC outcomes. 28 If we consider that PR has the highest self-reported prevalence of DM among all states and territories, 29 it is plausible that both higher rates of diabetes and obesity may contribute to the worse PC mortality in PR, although this requires formal testing. Altogether, the complex interplay between biology, exposures, and social factors has not yet been elucidated and needs to be addressed.…”

Association Between Obesity and Cancer Mortality: An Internal Medicine Outpatient Clinic Perspective

“…Kelkar and colleagues investigated the association between diabetes and prostate cancer-specific mortality. They found that diabetes was associated with increased risks of prostate cancer progression and mortality among obese men [ 51 ]. Similarly, Wu and colleagues reported that long-term plasma glucose fluctuation was significantly associated with the risk of cancer mortality (HR: 1.41 (95% CI: 1.04 - 1.92)), especially in the highest quartile of coefficient of variation of plasma glucose [ 52 ].…”

Diabetes mellitus susceptibility with varied diseased phenotypes and its comparison with phenome interactome networks

“…The understanding of association between DM and PCa is still insufficient. Moreover, obesity makes its pathophysiology a more complex situation[ 48 ].…”