Background Although diabetes is inversely related to prostate cancer (PC) risk, to the authors’ knowledge the impact of glycemic control on PC progression is unknown. In the current study, the authors tested the association between hemoglobin A1c (HbA1c) and long‐term PC outcomes among diabetic men undergoing radical prostatectomy (RP). Methods The authors retrospectively reviewed data regarding men undergoing RP from 2000 to 2017 at 8 Veterans Affairs hospitals. Diabetic patients were identified using International Classification of Diseases, Ninth Revision (ICD‐9) codes (250.x) or by an HbA1c value >6.5% at any time before RP. Cox models tested the association between HbA1c and biochemical disease recurrence (BCR), castration‐resistant PC (CRPC), metastases, PC‐specific mortality, and all‐cause mortality. The model for BCR was adjusted for multiple variables. Due to limited events, models for long‐term outcomes were adjusted for biopsy grade and prostate‐specific antigen only. Results A total of 1409 men comprised the study population. Of these, 699 patients (50%) had an HbA1c value <6.5%, 631 (45%) had an HbA1c value of 6.5% to 7.9%, and 79 (6%) had an HbA1c value ≥8.0%. Men with an HbA1c value ≥8.0% were younger (P < .001) and more likely to be black (P = .013). The median follow‐up after RP was 6.8 years (interquartile range, 3.7‐10.6 years). On multivariable analysis, HbA1c was not found to be associated with BCR. However, a higher HbA1c value was associated with metastasis (hazard ratio [HR], 1.21; 95% CI, 1.02‐1.44 [P = .031]) and CRPC (HR, 1.27; 95% CI, 1.03‐1.56 [P = .023]). Although not statistically significant, there were trends between higher HbA1c and risk of PC‐specific mortality (HR, 1.24; 95% CI, 0.99‐1.56 [P = .067]) and all‐cause mortality (HR, 1.09; 95% CI, 0.99‐1.19 [P = .058]). Conclusions Among diabetic men undergoing RP, a higher HbA1c value was associated with metastases and CRPC. If validated in larger studies with longer follow‐up, future research should test whether better glycemic control improves long‐term PC outcomes.

Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome. Molecular analysis of the patient's tumor through RNA sequencing showed high expression of several genes including CHGA, ASCL1, CALCA, HES6, PCSK1, CALCB and INSM1 confirming his neuroendocrine phenotype; elevated POMC expression was found, supporting the diagnosis of ectopic Cushing's syndrome.

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 &lt;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.

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Objective To assess the impact of a group medical clinic designed for patient with type 2 diabetes mellitus and hypertension on body mass index. Methods Using data from a randomized trial of 239 veterans with type 2 diabetes mellitus, we performed a secondary analysis using analysis of covariance mixed models to explore the effect of a 12-month group medical clinic intervention on change in body mass index vs. usual care. In an exploratory subgroup analysis, we compared change in body mass index between treatment arms stratified by whether patients had >0.5% reduction in hemoglobin A1c at 12 months. Results Baseline body mass index was 33.5 kg/m. At 12 months, there was no significant difference in change in body mass index between treatment arms (estimate=-0.02, 95% CI -0.51 to 5.05; P = 0.94); body mass index increased by approximately 0.20 points in both groups. There was also no significant difference in change in body mass index between treatment arms by whether or not patients had >0.5% reduction in hemoglobin A1c (estimate=-0.14, 95% CI -1.21 to -0.92; P = 0.79). Discussion Improved glycemic control was not associated with improved body mass index in the group medical clinic intervention. Given their positive effects on other outcomes, group medical clinics for patients with type 2 diabetes mellitus may be more beneficial if focus is shifted towards weight loss.