Hypoglycemia Unawareness, Type 1 Diabetes Mellitus
Conditions
Keywords
Type 1 Diabetes Mellitus, Hypoglycemia unawareness, 1H MRS, Lactate
Brief summary
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).
Interventions
OTHERhypoglycemia
Blood glucose levels will be kept at \ 3.0 mmol/l
OTHEReuglycemia
Blood glucose levels will be kept at \ 5.0 mmol/l
Sponsors
Dutch Diabetes Research Foundation
European Foundation for the Study of Diabetes
Radboud University Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain lactate concentration | during stable euglycemia and hypoglyemia | Concentration brain lactate measured with 1H-MRS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma lactate levels | during stable euglycemia and hypoglyemia | Concentration arterial plasma lactate |
| Hormone response | during stable euglycemia and hypoglyemia | — |
Countries
Netherlands
Outcome results
None listed