Ketoacidosis, Diabetes Mellitus Type 1
Conditions
Brief summary
Hypothesis 1. To define whether stimulation of ATGL and suppression of G0/G1 switch gene occur in the initial phases of diabetic ketoacidosis and thus can be identified as the primary mechanisms behind this life threatening condition. 2. Make a human model for studying ketoacidosis. The investigators plan to reduce in their regular insulin over night. In the morning we administer endotoxin, which together with a relative lack of insulin will initiate ketogenesis - a state of ketoacidosis. On another occasion strict glycemic control is imposed by means of intravenous insulin. The testing is done two separate days with at least 3 weeks in between and patients are admitted to hospital the evening before the day of testing. The investigators use isotopic tracers to determine metabolic fluxes and analyse fat (ATGL, G0/G1 switch gene) and muscle biopsies.
Interventions
BIOLOGICALLPS
LPS is endotoxin from gram negative bacteria. It is used scientifically to mimic infection lasting 4-8 hours.
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Diabetes type 1 * 19 \< BMI \< 26 * minimal or negative C-peptide * written consent
Exclusion criteria
* Severe comorbidity * regular medication apart from insulin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin signaling expressed as a CHANGE in phosphorylation of intracellular target proteins and CHANGE in mRNA expression of target genes in muscle- and fat-tissue. | Muscle and fat biopsies obtained on each study day (arm): t1= 6.45 (-75min) am t2=11.15 (195min) am t3= 12.30 pm (270min) | Change in phosphorylation of target proteins and messenger RNA (mRNA) expression of target genes assessed with western blotting technique. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies | Muscle and fat biopsies obtained on each study day (arm): t1= 6.45 am (-75min) t2=11.15 (195min) am t3= 12.30 pm (270min) | Muscle and fat at t1 and t2. Muscle biopsy at t3. Intracellular markers are assessed by western blotting. |
| Metabolism | Change in glucose, fat and protein metabolism between study days and during each study day | Change in glucose, fat and protein metabolism assessed by tracer kinetics on every study day (specific times below) and by indirect calorimetry. \[3H 3\]Glucose tracer from t=0 - 360min. Palmitic acid tracer from t=165min - 360min. Urea tracer from 0min - 240min. amino acid tracer from 60 min - 360 min. |
| Cytokines and stress hormones | In basal period t=0-240 minutes and in clamp period t=240-390 minutes | Measurement of immune response to endotoxin and hypoinsulinaemia. Estimating the whole body stress during ketoacidosis and pre ketoacidosis. |
Countries
Denmark
Outcome results
None listed