A Study of Intracellular Signaling in Muscle and Fat Cells During Ketosis
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|ClinicalTrials.gov Identifier: NCT02157155|
Recruitment Status : Completed
First Posted : June 5, 2014
Last Update Posted : December 2, 2015
- 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.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Ketoacidosis Diabetes Mellitus Type 1||Biological: LPS||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Crossover Assignment|
|Primary Purpose:||Basic Science|
|Official Title:||The Role of ATGL and G0/G1 Switch Gene Complex in Lipopolysaccaride (LPS) Induced Ketosis - a Controlled, Randomised, Clinical Experimental Study|
|Study Start Date :||June 2014|
|Actual Primary Completion Date :||March 2015|
|Actual Study Completion Date :||September 2015|
Insulin reduction and mimic infection with LPS
LPS is endotoxin from gram negative bacteria. It is used scientifically to mimic infection lasting 4-8 hours.
No Intervention: Control
Normal insulin and no LPS
- 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. [ Time Frame: 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.
- Change in Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02157155
|Aarhus University Hospital|
|Aarhus, Denmark, 8000|
|Principal Investigator:||Mads Svart, MD||Aarhus University / Aarhus University Hospital|
|Study Chair:||Niels Møller, MD||Aarhus University / Aarhus University Hospital|