Metabolic Effects of Exogenous 3-hydroxybutyrate in Patients With Type 1 Diabetes and Healthy Controls

Not Applicable

Completed

• Conditions: Diabetic Ketoacidosis; Type 1 Diabetes Mellitus
• Interventions: Biological: 3-hydroxybutyrate

• Registration Number: NCT04656236
• Lead Sponsor: University of Aarhus

Brief Summary

The main objective of this clinical trial is to study the metabolic effects of intravenous infusion of the ketone body, 3-hydroxybutyrate (3-OHB), in patients with type 1 diabetes and healthy control subjects. Moreover, the investigators plan to examine regulatory mechanisms of 3-OHB that may be related to diabetic ketoacidosis.

The hypotheses are:

1. 3-OHB related inhibition of lipolysis is impaired in patients with type 1 diabetes.

2. Intravenous infusion of 3-OHB affects signaling pathways involved in the metabolic regulation in patients with type 1 diabetes and healthy controls.

3. 3-OHB infusion improves cardiac function in patients with type 1 diabetes and healthy controls.

The effects of 3-OHB will be investigated by isotopic tracers examinations, fat and muscle biopsies and blood samples. To evaluate effects on cardiac function echocardiography will be performed.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-11-30
• Study First Submitted QC: 2020-11-30
• Study First Posted: 2020-12-07
• Study Start: 2021-01-01
• Status Verified: 2021-12
• Primary Completion: 2022-03-01
• Study Completion: 2022-03-01
• Last Update Submitted: 2022-03-07
• Last Update Posted: 2022-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 20

Inclusion Criteria

• Type 1 diabetes diagnosis
• C-peptide negative
• 19 < BMI < 26
• written consent

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Exclusion Criteria

• Severe comorbidity
• Regular medication apart from insulin (except over-the-counter medicines)
• Use of long acting insulin analogues, that work > 24 hours, e.g. Tresiba
• PI finds the patient not fit (e.g. mental illness, too nervous, unacceptable screening blood tests or other).

Healthy control subjects:

Inclusion Criteria:

• 19 < BMI < 26
• written consent

Exclusion Criteria:

• Chronic disease
• Regular medication (except over-the-counter medicines)
• PI finds the patient not fit (e.g. mental illness, too nervous, unacceptable screening blood tests or other).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Control	3-hydroxybutyrate	3 hours of continuously intravenous infusion of saline (NaCl).
Intervention	3-hydroxybutyrate	3 hours of continuously intravenous infusion of 3-hydroxybutyrate.

Primary Outcome Measures

Name	Time	Method
Differences in lipolysis rate	After 3 hours of interventions	Measured as differences in palmitate flux

Secondary Outcome Measures

Name	Time	Method
Differences in circulating concentrations of 3-hydroxybutyrate, glucose, free fatty acids, insulin, glucagon and C-peptide	During the 3 hours intervention period	Blood samples
Changes in protein metabolism	After 3 hours of interventions	Measured as differences in forearm and whole body tracer kinetics
Changes in glucose kinetics	After 3 hours of interventions	Measured by glucose tracer.
Cardiac function	After 2-3 hours of interventions	Changes in cardiac output and left ventricular ejection fraction measured by echocardiography
Changes in signaling in muscle and adipose tissue	After 1,5-3 hours of interventions	Western blot examinations of muscle and adipose tissue biopsies

Trial Locations

Locations (1)

Steno diabetes center Aarhus; 🇩🇰 Aarhus, Denmark