Metabolic Changes in Androgen-Deprived Nondiabetic Men With Prostate Cancer Are Not Mediated by Cytokines or aP2.

Abstract

Androgen deprivation therapy (ADT) remains the cornerstone of management of prostate cancer (PCa). Previous studies have shown that men undergoing ADT develop insulin resistance and diabetes, but the mechanisms behind ADT-induced metabolic abnormalities remain unclear. To evaluate the role of inflammatory cytokines and adipocyte protein-2 (aP2) in ADT-induced metabolic dysfunction. This 6-month prospective cohort study enrolled nondiabetic men with PCa about to undergo ADT (ADT group) and a control group of nondiabetic men who had previously undergone prostatectomy for localized PCa and were in remission (non-ADT group); all participants had normal testosterone at study entry. Fasting blood samples were collected at baseline and at 6, 12, and 24 weeks after initiation of ADT and at the same intervals in the non-ADT group. Glucose, insulin, lipids, inflammatory cytokines, and C-reactive protein were measured. We also measured serum aP2, an adipocyte-secreted protein that promotes hepatic glucose production. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Seventy-three participants formed the analytical sample (33 ADT, 40 non-ADT). HOMA-IR increased in the ADT group (estimated change = 0.25; P = 0.05), but was unchanged in the non-ADT group (0.11; P = 0.342). Serum concentrations of inflammatory cytokines or aP2 did not change significantly. There was a treatment-associated increase in total (16 mg/dL; P < 0.001), high-density lipoprotein (8 mg/dL; P < 0.001), and low-density lipoprotein (7 mg/dL; P = 0.02) cholesterol. ADT-induced metabolic abnormalities were not associated with changes in circulating inflammatory cytokines or aP2 levels.