Objective: Subthalamic nucleus-deep brain stimulation (STN-DBS) is an alternative treatment for patients with uncontrolled symptoms of Parkinson's disease (PD), but it has other nonmotor impact. Because STN-DBS alters the energy expenditure in humans, we hypothesized that STN-DBS may affect postabsorptive glucose metabolism in patients with PD. Research Design and Methods: Endogenous glucose production (EGP) and whole-body glucose disposal rates (GDRs) were assessed in the postabsorptive state during a primed continuous iv infusion of D-[6,6-H-2(2)] glucose for 5 hours in 8 STN-DBS-treated patients with PD, without (Stim-OFF) and during STN-DBS (Stim-ON) treatment. EGP and GDR in PD patients were compared with glucose kinetics of 8 matched healthy control subjects. Plasma concentrations of insulin, glucagon, and free fatty acids were also determined. Results: EGP and GDR were higher in PD patients in Stim-OFF conditions than in the control group (2.62 +/- 0.09 vs 2.27 +/- 0.10 mg/kg.min, P < .05). Despite no significant changes in blood glucose throughout the kinetic study, a significant and consistent 22% decrease in EGP occurred in PD patients during Stim-ON (2.04 +/- 0.07 mg/kg(-1).min(-1); P < .01), and whole-body glucose kinetics in Stim-ON patients were no more different from those of the control subjects (P = NS). No difference in insulin, glucagon, or free fatty acid concentrations was observed in the patients between Stim-OFF and Stim-ON conditions. Conclusions: Deep brain stimulation in patients with PD affects EGP glucose disposal, suggesting that a cross talk between the central nervous system and peripheral tissues may regulate glucose homeostasis.