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

University of Aarhus20 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Type 1 Diabetes Mellitus Diabetic Ketoacidosis

Interventions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Patients with type 1 diabetes: Inclusion Criteria: * Type 1 diabetes diagnosis * C-peptide negative * 19 \< BMI \< 26 * written consent 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).

Outcomes

Primary Outcomes

Differences in lipolysis rate

Measured as differences in palmitate flux

Time frame: After 3 hours of interventions

Secondary Outcomes

Changes in protein metabolism

Measured as differences in forearm and whole body tracer kinetics

Time frame: After 3 hours of interventions

Changes in glucose kinetics

Measured by glucose tracer.

Time frame: After 3 hours of interventions

Cardiac function

Changes in cardiac output and left ventricular ejection fraction measured by echocardiography

Time frame: After 2-3 hours of interventions

Changes in signaling in muscle and adipose tissue

Western blot examinations of muscle and adipose tissue biopsies

Time frame: After 1,5-3 hours of interventions

Differences in circulating concentrations of 3-hydroxybutyrate, glucose, free fatty acids, insulin, glucagon and C-peptide

Blood samples

Time frame: During the 3 hours intervention period

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes