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

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).

Conditions

• Type 1 Diabetes Mellitus
• Hypoglycemia Unawareness

Interventions

OTHER

hypoglycemia

Blood glucose levels will be kept at \~3.0 mmol/l

OTHER

euglycemia

Blood glucose levels will be kept at \~5.0 mmol/l

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

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-08-31

Primary Completion

2015-10-31

Completion

2015-10-31

Countries

• Netherlands

Study Locations