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

Not Applicable

Completed

• Conditions: Type 1 Diabetes Mellitus; Hypoglycemia Unawareness
• Interventions: Other: hypoglycemia; Other: euglycemia

• Registration Number: NCT02146404
• Lead Sponsor: Radboud University Medical Center

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-05-21
• Study First Submitted QC: 2014-05-22
• Study First Posted: 2014-05-23
• Study Start: 2014-08
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Status Verified: 2015-11
• Last Update Submitted: 2015-11-09
• Last Update Posted: 2015-11-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Hypoglycemia	hypoglycemia	Plasma glucose levels will be clamped at a stable value of \~3.0 mmol/l
Euglycemia	euglycemia	Plasma glucose levels will be clamped at a constant value of \~5.0 mmol/l

Primary Outcome Measures

Name	Time	Method
Brain lactate concentration	during stable euglycemia and hypoglyemia	Concentration brain lactate measured with 1H-MRS

Secondary Outcome Measures

Name	Time	Method
Plasma lactate levels	during stable euglycemia and hypoglyemia	Concentration arterial plasma lactate
Hormone response	during stable euglycemia and hypoglyemia

Trial Locations

Locations (1)

Radboud umc; 🇳🇱 Nijmegen, Netherlands