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

Study Overview
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Brief Summary
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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: 3-OHB related inhibition of lipolysis is impaired in patients with type 1 diabetes. Intravenous infusion of 3-OHB affects signaling pathways involved in the metabolic regulation in patients with type 1 diabetes and healthy controls. 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.

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

Conditions
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Type 1 Diabetes Mellitus, Diabetic Ketoacidosis

Intervention / Treatment
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* Biological: 3-hydroxybutyrate


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover design in 2 different groups, patients with type 1 diabetes and healthy controls.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>3 hours of continuously intravenous infusion of 3-hydroxybutyrate. | Biological: 3-hydroxybutyrate<br>* 3-hydroxybutyrate is a metabolite, produced in the human body.<br>|
| Placebo Comparator: Control<br>3 hours of continuously intravenous infusion of saline (NaCl). | Biological: 3-hydroxybutyrate<br>* 3-hydroxybutyrate is a metabolite, produced in the human body.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in lipolysis rate | Measured as differences in palmitate flux | After 3 hours of interventions | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in protein metabolism | Measured as differences in forearm and whole body tracer kinetics | After 3 hours of interventions | 
| Changes in glucose kinetics | Measured by glucose tracer. | After 3 hours of interventions | 
| Cardiac function | Changes in cardiac output and left ventricular ejection fraction measured by echocardiography | After 2-3 hours of interventions | 
| Changes in signaling in muscle and adipose tissue | Western blot examinations of muscle and adipose tissue biopsies | 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 | During the 3 hours intervention period |