Radboud umc
Nijmegen, Netherlands
NCT Number: NCT02308293
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, eventually leading to hypoglycemia unawareness, which creates a particularly high risk of severe hypoglycemia. Recent evidence suggest a pivotal role for (brain) lactate in the pathogenesis of hypoglycemia unawareness. Indeed, exogenous lactate administration may preserve brain function and attenuate counterregulatory responses to and symptomatic awareness of hypoglycemia. It is unknown whether endogenous elevation of plasma lactate produces the same effects and whether such effects differ between patients with T1DM with and without hypoglycemia unawareness and healthy controls.
Objective: To investigate the effect of elevated levels of endogenous lactate on brain lactate accumulation and on counterregulatory responses to, symptomatic awareness of and cognitive function during hypoglycemia in patients with T1DM with and without hypoglycemia unawareness and normal controls.
Hypothesis: The investigators hypothesize first that endogenous lactate, when raised through high intensity exercise, preserves neuronal metabolism during subsequent hypoglycemia, which in turn will attenuate counterregulatory hormone responses, appearance of symptoms and deterioration of cognitive function. Second, the investigators posit that these effects will be augmented in patients with hypoglycemia unawareness compared to healthy subjects and T1DM patients with normal awareness as a consequence of greater transport capacity of lactate into the brain.
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Notify Me18 year–40 year
All sexes
Interventional
Not applicable
Nijmegen, Netherlands
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
for healthy subjects
Inclusion criteria
T1DM patients with normal hypoglycemic awareness
Inclusion criteria
T1DM patients with hypoglycemia unawareness
Exclusion criteria
Additional exclusion criteria for all T1DM patients:
3x30 seconds 'all out' sprints
rest
Time frame: during 60 m of hypoglycemia
Time frame: During 60 min hypoglycemia
Levels of counter-regulatory hormones measured in arterial plasma
Time frame: During 60 min hypoglycemia
Amount of glucose 20% necessary to maintain plasma glucose at steady state values
Time frame: During 60 min hypoglycemia
Lactate levels measured in arterial plasma
Time frame: During 60 min hypoglycemia
Cognitive test will be: Dutch State Trait Anxiety Inventory, Digit Span, Stroop color word test, word fluency test, trail making test and Pasat
Time frame: During 60 min hypoglycemia
levels of cytokines
Time frame: During 60 min hypoglycemia
Brain perfusion measured with ASL-MRI
Time frame: During 60 min of hypoglycemia
Brain lactate levels measured with 1H-MRS
Time frame: During 60 min hypoglycemia
Plasma glucose concentration, necessary to adjust glucose infusion rate
Time frame: During 60 min hypoglycemia
Insulin levels, measured in arterial plasma
Radboud University Medical Center
Other
The Effect of Exercise-induced Hyperlacticacidemia on Counterregulatory Responses, Symptoms, Cognitive Function and Brain Lactate Accumulation During Hypoglycemia in (Hypoglycemic Unaware)Type I Diabetes Patients and Normal Controls
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