The Effect of Hypoglycaemia on Brain Lactate Accumulation and Cerebral Blood Flow

Radboud University Medical Center

Status

Completed

Conditions

Type 1 Diabetes Mellitus

Hypoglycemia Unawareness

Treatments

Other: euglycemia

Other: hypoglycemia

Study type

Interventional

Funder types

Other

Identifiers

NCT02146404

1H_lac_acc

Details and patient eligibility

About

Iatrogenic hypoglycemia is the most frequent acute complication of insulin therapy in people with type 1 diabetes (T1DM). Recurrent hypoglycemic events initiate a process of habituation, characterized by suppression of hypoglycemic symptoms and lead to hypoglycemia unawareness, which in itself defines a particularly high risk of severe hypoglycemia. Recent evidence suggest a pivotal role for increased brain lactate transport capacity in the pathogenesis of hypoglycemia unawareness. However, there is uncertainty about the magnitude of this effect and whether such excess brain lactate is oxidizes as a glucose-sparing alternative energy source or acts as a metabolic regulator controlling brain glucose metabolism, oxygen consumption and cerebral blood flow.

Objective: The primary objective of this study is to investigate the effect of hypoglycemia on brain lactate accumulation and regional cerebral blood perfusion in humans. The secondary objective is to assess whether this effect is a related to hypoglycemia unawareness or a consequence of T1DM per se.

Hypothesis: The investigators hypothesize that hypoglycemia stimulates lactate transport over the blood-brain barrier leading to cerebral lactate accumulation and that this lactate accumulation is a function of prior hypoglycemic exposure frequency contributing to clinical hypoglycemia unawareness. Furthermore, the investigators expect that this effect of hypoglycemia on brain lactate accumulation is related to changes in cerebral blood flow (CBF).

Enrollment

21 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria for healthy subjects

Age: 18-50 years
Body-Mass Index: 18-30 kg/m2
Blood pressure: <160/90 mmHg

Inclusion criteria T1DM patients with normal hypoglycemic awareness

Diabetes duration ≥ 1 year
Age: 18-50 years
Body-Mass Index: 18-30 kg/m2
HbA1c: 42-75 mmol/mol (6-9%)
Outcome Clarke questionnaire: 0-1
Blood pressure: <160/90 mmHg

Inclusion criteria T1DM patients with hypoglycemia unawareness

Diabetes duration ≥ 1 year
Age: 18-50 years
Body-Mass Index: 18-30 kg/m2
HbA1c: 42-75 mmol/mol (6-9%)
Outcome Clarke questionnaire: >3
Blood pressure: <160/90 mmHg

Exclusion criteria for healthy subjects

Inability to provide informed consent
Presence of any medical condition that might interfere with the study protocol, such as brain injuries, epilepsy, a major cardiovascular disease event or anxiety disorders
Use of any medication, except for oral contraceptives
MR(I) contraindications (pregnancy, severe claustrophobia, metal parts in body)

Exclusion criteria for all T1DM patients

Inability to provide informed consent
Presence of any other medical condition that might interfere with the study protocol, such as brain injuries, epilepsy, a major cardiovascular disease event, anxiety disorders, or complications of T1DM (including neuropathy and retinopathy)
Use of any other medication than insulin, except for oral contraceptives or stable thyroxine supplementation therapy
MR(I) contraindications (pregnancy, severe claustrophobia, metal parts in body)