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Completed

NCT Number: NCT02157155

A Study of Intracellular Signaling in Muscle and Fat Cells During Ketosis

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.

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Key information

Conditions

Ketoacidosis Acid-Base Imbalance Acidosis Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus Type 1 Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Ketosis Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Aarhus University Hospital

Aarhus, 8000, Denmark

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diabetes type 1
  • 19 < BMI < 26
  • minimal or negative C-peptide
  • written consent

Exclusion criteria

  • Severe comorbidity
  • regular medication apart from insulin

Treatment and study plan

LPS

Biological

LPS is endotoxin from gram negative bacteria. It is used scientifically to mimic infection lasting 4-8 hours.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

Sponsors and collaborators

Lead sponsor

University of Aarhus

Other

Registry information

Official study title

The Role of ATGL and G0/G1 Switch Gene Complex in Lipopolysaccaride (LPS) Induced Ketosis - a Controlled, Randomised, Clinical Experimental Study

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Jun 5, 2014
Registry last updated
Dec 2, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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