The Effect Lactate Administration on Cerebral Blood Flow During Hypoglycemia
Status:
Unknown status
Trial end date:
2019-06-11
Target enrollment:
Participant gender:
Summary
It is thought that altered brain lactate handling is involved in the development of impaired
awareness of hypoglycemia (IAH), i.e. the inability to timely detect hypoglycemia in people
with type 1 diabetes (T1DM). Infusion of lactate diminishes symptomatic and hormonal
responses to hypoglycemia in patients with normal awareness of hypoglycemia (NAH), resembling
the situation of patients with IAH. It is unknown whether this attenuating effect is due to
brain lactate oxidation or the result of lactate-induced alterations of global and regional
cerebral blood flow (CBF).
Normally, hypoglycemia causes a redistribution of CBF towards the thalamus, from where the
sympathetic response to hypoglycemia is coordinated, but in IAH this effect is absent and
global CBF is increased. We hypothesize that lactate infusion in patients with NAH will
result in blunting of thalamic activation and/or enhanced global CBF. If so, these results
may help delineating the pathogenesis of IAH which eventually creates new avenues to protect
against the morbidity associated with hypoglycemia and IAH.
Study design: Single-blind placebo controlled, randomized cross-over intervention study Study
population: T1DM patients with NAH (n=10) Intervention: On two separate occasions, patients
with T1DM and NAH will undergo a hyperinsulinemic euglycemic-hypoglycemic glucose clamp with
or without the infusion of exogenous lactate. ASL-MRI will be applied to measure global and
regional changes in CBF.
Main study parameters/endpoints: The change in regional thalamic CBF in response to
intravenous lactate infusion compared to placebo, during hypoglycemia