Changes in regional brain F-18-fluorodeoxyglucose uptake at hypoglycemia in type 1 diabetic men associated with hypoglycemia unawareness and counter-regulatory failure

We examined the effects of acute moderate hypoglycemia and the condition of hypoglycemia unawareness on regional brain uptake of the labeled glucose a nalog [F-18]fluorodeoxyglucose (FDG) using positron emission tomography (PE T). FDG-PET was performed in diabetic patients with (n = 6) and without (n = 7) hypoglycemia, awareness. Each patient was studied at plasma glucose le vels of 5 and 2.6 mmol/l, applied by glucose clamp techniques, in random or der. Hypoglycemia-unaware patients were asymptomatic during hypoglycemia, w ith marked attenuation of their epinephrine responses (mean [+/- SD] peak o f 0.77 +/- 0.39 vs. 7.52 +/- 2.9 nmol/l; P < 0.0003) and a reduced global b rain FDG uptake ([mean +/- SE] 2.592 +/- 0.188 vs. 2.018 +/- 0.174 at eugly cemia; P = 0.027). Using statistical parametric mapping (SPM) to analyze im ages of FDG uptake, we identified a subthalamic brain region that exhibited significantly different behavior between the aware and unaware groups. In the aware group, there was little change in the normalized FDG uptake in th is region in response to hypoglycemia ([mean +/- SE] 0.654 +/- 0.016 to 0.6 36 +/- 0.013; NS); however, in the unaware group, the uptake in this region fell from 0.715 +/- 0.015 to 0.623 +/- 0.012 (P = 0.001). Our data were co nsistent with the human hypoglycemia sensor being anatomically located in t his brain region, and demonstrated for the first time a change in its metab olic function associated. with the failure to trigger a counter-regulatory response.