NCT02308293

The Role of Endogenous Lactate in Brain Preservation and Counterregulatory Defenses Against Hypoglycemia

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Radboud University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

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, 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.

Conditions

• Type 1 Diabetes Mellitus
• Hypoglycemia Unawareness

Interventions

Type	Name	Description
BEHAVIORAL	High intensity exercise	3x30 seconds 'all out' sprints
BEHAVIORAL	Lay down comfortably	rest

Timeline

• Start date: 2015-01-01
• Primary completion: 2016-05-01
• Completion: 2016-07-01
• First posted: 2014-12-04
• Last updated: 2016-11-25

Locations

1 site across 1 country: Netherlands