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Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01919788
First Posted: August 9, 2013
Last Update Posted: February 24, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Thomas Schmidt Voss, University of Aarhus
August 5, 2013
August 9, 2013
February 24, 2016
August 2013
April 2014   (Final data collection date for primary outcome measure)
Insulin and growth hormone signalling, expressed as CHANGE in phosphorylation of intracellular target proteins and mRNA expression of target genes in muscle- and fat-tissue. [ Time Frame: Biopsies obtained on each study day (arm). Muscle biopsies: time (t)= -30min, t= 30min and t= 75min. Fat biopsies: t= 30min and t= 75min ]
Change in phosphorylation of target proteins and mRNA expression of target genes assessed with western blotting technique.
Same as current
Complete list of historical versions of study NCT01919788 on ClinicalTrials.gov Archive Site
  • Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies. [ Time Frame: Biopsies obtained on each study day (arm). Muscle biopsies: time (t)= -30min, t= 30min and t= 75min. Fat biopsies: t= 30min and t= 75min ]
    Assessed by Western blotting.
  • Metabolism. [ Time Frame: measured twice on each study day (arm) at t= -30-0 min. and t= 50-80 min. ]
    Assessment of glucose metabolism by forearm pletysmography and heated hand technique (duration of pletysmography = 30 min.)
  • Ghrelin [ Time Frame: Measured at t = -30min., t=0min, t=15min, t= 30min., t=45min., t=60min., t= 75min., t=90min. and t=105min. on each study day (arm) ]
  • Metabolism [ Time Frame: once per study day (arm): t 45min - 105min. ]
    A palmitic acid tracer will be given once per trial day to estimate fatty acid metabolism. Duration 1 hour.
  • Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies. [ Time Frame: Biopsies obtained on each study day (arm). Muscle biopsies: time (t)= -30min, t= 30min and t= 75min. Fat biopsies: t= 30min and t= 75min ]
    Assessed by Western blotting.
  • Metabolism. [ Time Frame: measured twice on each study day (arm) at t= -30-0 min. and t= 50-80 min. ]
    Assessment of glucose metabolism by forearm pletysmography and heated hand technique (duration of pletysmography = 30 min.)
  • Ghrelin [ Time Frame: Measured at t = -30min., t= 30min., t= 75min. and t=110min. on each study day (arm) ]
  • Metabolism [ Time Frame: once per study day (arm): t 45min - 105min. ]
    A palmitic acid tracer will be given once per trial day to estimate fatty acid metabolism. Duration 1 hour.
Not Provided
Not Provided
 
Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose
Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose

Diabetes mellitus type I (DMI) is characterized by lack of endogenous insulin and these patients are 100% dependent on insulin substitution to survive. Diabetes mellitus type II (DMII) is characterized by reduced insulin sensitivity and sometimes also reduced insulin production, thus patients with DMII might also be dependent on insulin substitution.

Insulin is produced in- and secreted from the pancreas when blood glucose concentration rises during- and after a meal. Insulin increases cellular uptake of glucose leading to lower blood glucose concentration. Substitution with insulin is/can be necessary in DM, but at the same time it induces the risk of hypoglycemia. This makes treatment with insulin a balancing act between hyper- and hypoglycemia.

A hypoglycemic episode is a dreaded consequence of insulin overdosing, and also a very frequent reason for hospital admission in patients with DM. Examples of hypoglycemic symptoms may be; shaking, a sense of hunger, sweating, irritability progressing to lack of relevant cerebral responses and eventually coma, convulsions and possibly death. People with diabetes lose the ability to sense of low blood glucose with time, because of a lack of appropriate counter-regulatory responses, hereby increasing the risk of severe hypoglycemia. Understanding normal physiologic counter regulatory mechanisms during hypoglycemia is of major importance to patients with DM and has the potential to change medical treatment in diabetes, to reduce the risk of hypoglycemia.

Hypothesis: Hypoglycemia counteracts insulin signaling via hormone-dependent intracellular counter-regulatory mechanisms, involving phosphorylation of specific signaling proteins.

Aim: To define counter-regulatory mechanisms in muscle- and fat tissue during hypoglycemia, and to investigate the effect of insulin on lipid metabolism in healthy- and type I diabetic subjects.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
  • Diabetes Mellitus Type I.
  • Hypoglycemia.
  • Drug: Insulin (Insuman Rapid)
  • Drug: Glucose
  • Other: Saline
  • Placebo Comparator: Control

    No insulin administered. Instead of insulin infusion, a small amount of saline is administered to keep the subject blinded.

    Three muscle biopsies and two fat biopsies will be obtained. A palmitic acid tracer will be given to estimate fatty acid metabolism. Forearm pletysmography will be performed twice.

    Intervention: Other: Saline
  • Experimental: Insulin
    Insulin (Insuman Rapid) is administered once as a bolus of 0,1 IU/kg. Three muscle biopsies and two fat biopsies will be obtained. A palmitic acid tracer will be given to estimate fatty acid metabolism Forearm pletysmography will be performed twice
    Intervention: Drug: Insulin (Insuman Rapid)
  • Experimental: Insulin and glucose

    Insulin (Insuman rapid) is administered once as a bolus injection of 0,1 IU/kg and glucose is given at the same time to avoid hypoglycemia in this arm.

    Three muscle biopsies and to fat biopsies is obtained. A palmitic acid tracer is given to estimate fatty acid metabolism Forearm pletysmography will be performed twice

    Interventions:
    • Drug: Insulin (Insuman Rapid)
    • Drug: Glucose
Voss TS, Vendelbo MH, Kampmann U, Pedersen SB, Nielsen TS, Johannsen M, Svart MV, Jessen N, Møller N. Effects of insulin-induced hypoglycaemia on lipolysis rate, lipid oxidation and adipose tissue signalling in human volunteers: a randomised clinical study. Diabetologia. 2017 Jan;60(1):143-152. Epub 2016 Oct 12.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
9
April 2014
April 2014   (Final data collection date for primary outcome measure)
  • BMI > 19 and < 26
  • Written Consent

Exclusion Criteria:

  • Epilepsy
  • Cardiac arrythmia
  • Ischemic heart disease
  • Other medical illness
Sexes Eligible for Study: Male
18 Years and older   (Adult, Senior)
Yes
Contact information is only displayed when the study is recruiting subjects
Denmark
 
 
NCT01919788
VEK journal nr.: M-2013-113-13
VEK Journal nr. M-2013-113-13 ( Other Identifier: VEK )
No
Not Provided
Not Provided
Thomas Schmidt Voss, University of Aarhus
University of Aarhus
Not Provided
Study Chair: Niels Møller, MD Aarhus University / Aarhus University Hospital
Principal Investigator: Thomas Voss, MD Aarhus University / Aarhus University Hospital
University of Aarhus
February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP