Blood-to-brain glucose transport and cerebral glucose metabolism are not reduced in poorly controlled type 1 diabetes

To test the hypothesis that blood-to-brain glucose transport is reduced in poorly controlled type 1 diabetes, we studied seven patients with a mean (± SD) HbA(1c) level of 10.1 ± 1.2% and nine nondiabetic subjects during hyperinsulinemic, mildly hypoglycemic (~3.6 mmol/l, ~65 mg/dl) glucose clamps. 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 injection of [1-¹¹C]glucose using a model that includes a fourth rate constant to account for regional egress of ¹¹C metabolites. Cerebral blood flow and cerebral blood volume were determined with intravenous H2¹⁵O and inhaled C¹⁵O, respectively, also by PET. At plateau plasma glucose concentrations of 3.6 ± 0.0 and 3.7 ± 0.1 mmol/l, rates of blood-to-brain glucose transport were similar in the two groups (23.7 ± 2.2 and 21.6 ± 2.9 μmol. 100 g^-1 min^-1, P = 0.569, in the control subjects and the patients, respectively). There were also no differences in the rates of cerebral glucose metabolism (16.8 ± 0.8 and 16.3 ± 1.2 μmol. 100g^-1 min^-1, P = 0.693, respectively). Plasma epinephrine (1,380 ± 340 vs. 450 ± 170 pmol/l, P = 0.0440) and glucagon (26 ± 5 vs. 12 ± 1 pmol/l, P = 0.0300) responses to mild hypoglycemia were reduced in the patients with type 1 diabetes. We conclude that neither blood-to-brain glucose transport nor cerebral glucose metabolism is measurably reduced in people with poorly controlled type 1 diabetes.