Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Thomas Schmidt Voss, University of Aarhus
ClinicalTrials.gov Identifier:
NCT01919788
First received: August 5, 2013
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Diabetes Mellitus Type I.
Hypoglycemia.
Drug: Insulin (Insuman Rapid)
Drug: Glucose

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Change in phosphorylation of target proteins and mRNA expression of target genes assessed with western blotting technique.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Assessed by Western blotting.

  • Metabolism. [ Time Frame: measured twice on each study day (arm) at t= -30-0 min. and t= 50-80 min. ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
  • Metabolism [ Time Frame: once per study day (arm): t 45min - 105min. ] [ Designated as safety issue: No ]
    A palmitic acid tracer will be given once per trial day to estimate fatty acid metabolism. Duration 1 hour.


Enrollment: 9
Study Start Date: August 2013
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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
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

Drug: Insulin (Insuman Rapid) Drug: Glucose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria
  • BMI > 19 and < 26
  • Written Consent

Exclusion Criteria:

  • Epilepsy
  • Cardiac arrythmia
  • Ischemic heart disease
  • Other medical illness
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01919788

Locations
Denmark
Institute of Clinical Medicine
Aarhus, Aarhus C, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Investigators
Study Chair: Niels Møller, MD Aarhus University / Aarhus University Hospital
Principal Investigator: Thomas Voss, MD Aarhus University / Aarhus University Hospital
  More Information

No publications provided

Responsible Party: Thomas Schmidt Voss, MD, University of Aarhus
ClinicalTrials.gov Identifier: NCT01919788     History of Changes
Other Study ID Numbers: VEK journal nr.: M-2013-113-13, VEK Journal nr. M-2013-113-13
Study First Received: August 5, 2013
Last Updated: May 15, 2014
Health Authority: Denmark: Ethics Committee
Denmark: Danish Dataprotection Agency

Keywords provided by University of Aarhus:
Diabetes Mellitus Type I
Hypoglycemia
Counter-regulatory mechanisms

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014