Diabetic Ketoacidosis, Type 1 Diabetes Mellitus
Conditions
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.
Interventions
BIOLOGICAL3-hydroxybutyrate
3-hydroxybutyrate is a metabolite, produced in the human body.
Sponsors
Aarhus University Hospital
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Crossover design in 2 different groups, patients with type 1 diabetes and healthy controls.
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences in lipolysis rate | After 3 hours of interventions | Measured as differences in palmitate flux |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in glucose kinetics | After 3 hours of interventions | Measured by glucose tracer. |
| Changes in protein metabolism | After 3 hours of interventions | Measured as differences in forearm and whole body tracer kinetics |
| 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 |
| Differences in circulating concentrations of 3-hydroxybutyrate, glucose, free fatty acids, insulin, glucagon and C-peptide | During the 3 hours intervention period | Blood samples |
Countries
Denmark
Outcome results
None listed