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

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

BEHAVIORAL

High intensity exercise

3x30 seconds 'all out' sprints

BEHAVIORAL

Lay down comfortably

rest

Sponsors & Collaborators

• Dutch Diabetes Research Foundation

  collaborator OTHER

• European Foundation for the Study of Diabetes

  collaborator OTHER

• Radboud University Medical Center

  lead OTHER

Principal Investigators

• Bastiaan de Galan, Dr. · Radboud University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2015-01-31

Primary Completion

2016-05-31

Completion

2016-07-31

Countries

• Netherlands

Study Locations