Blood-to-brain glucose transport, cerebral glucose metabolism, and cerebral blood flow are not increased after hypoglycemia

Recent antecedent hypoglycemia has been found to shift glycemic thresholds for autonomic (including adrenomedullary epinephrine), symptomatic, and oth er responses to subsequent hypoglycemia to lower plasma glucose concentrati ons. This change in threshold is the basis of the clinical syndromes of hyp oglycemia unawareness and, in part, defective glucose counterregulation and the unifying concept of hypoglycemia-associated autonomic failure in type I diabetes. We tested in healthy young adults the hypothesis that recent an tecedent hypoglycemia increases blood-to-brain glucose transport, a plausib le mechanism of this phenomenon. Eight subjects were studied after euglycem ia, and nine were studied after similar to 24 h of interprandial hypoglycem ia (similar to 55 mg/dl, similar to3.0 mmol/l). The latter were shown to ha ve reduced plasma epinephrine (P = 0.009), neurogenic symptoms (P = 0.009), and other responses to subsequent hypoglycemia. Global bihemispheric blood -to-brain glucose transport and cerebral glucose metabolism were calculated from rate constants derived from blood and brain time-activity curves-the latter determined by positron emission tomography (PET)-after intravenous i njection of [1-C-11]glucose at clamped plasma glucose concentrations of 65 mg/dl (3.6 mmol/l). For these calculations, a model was used that includes a fourth rate constant to account for egress of [C-11] metabolites. Cerebra l blood flow was measured with intravenous [O-15]water using PET. After eug lycemia and after hypoglycemia, rates of blood-to-brain glucose transport ( 24.6 +/- 2.3 and 22.4 +/- 2.4 mu mol.100 g(-1).min(-1), respectively), cere bral glucose metabolism (16.8 +/- 0.9 and 15.9 +/- 0.9 mu mol.100 g(-1).min (-1), respectively) and cerebral blood flow (56.8 +/- 3.9 and 53.3 +/- 4.4 ml.100 g(-1).min(-1), respectively) were virtually identical. These data do not support the hypothesis that recent antecedent hypoglycemia increases b lood-to-brain glucose transport during subsequent hypoglycemia. They do not exclude regional increments in blood-to-brain glucose transport. Alternati vely, the fundamental alteration might lie beyond the blood-brain barrier.