Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose

Hypoglycemia Clinical Trial

Official title:

Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01919788
• Other study ID #: VEK journal nr.: M-2013-113-13
• Secondary ID: VEK Journal nr.
• Status: Completed
• Phase: N/A
• Start date: August 2013
• Est. completion date: April 2014

Study information

• Verified date: September 2019
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

• BMI > 19 and < 26

• Written Consent

Exclusion Criteria:

• Epilepsy

• Cardiac arrythmia

• Ischemic heart disease

• Other medical illness

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Type I
• Diabetes Mellitus, Type 1
• Hypoglycemia

Intervention

Drug:
• Insulin (Insuman Rapid)

• Glucose

Other:
• Saline

Locations

Country	Name	City	State
Denmark	Institute of Clinical Medicine	Aarhus	Aarhus C

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Change in phosphorylation of target proteins and mRNA expression of target genes assessed with western blotting technique.	Biopsies obtained on each study day (arm). Muscle biopsies: time (t)= -30min, t= 30min and t= 75min. Fat biopsies: t= 30min and t= 75min
Secondary	Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies.	Assessed by Western blotting.	Biopsies obtained on each study day (arm). Muscle biopsies: time (t)= -30min, t= 30min and t= 75min. Fat biopsies: t= 30min and t= 75min
Secondary	Metabolism.	Assessment of glucose metabolism by forearm pletysmography and heated hand technique (duration of pletysmography = 30 min.)	measured twice on each study day (arm) at t= -30-0 min. and t= 50-80 min.
Secondary	Ghrelin		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)
Secondary	Metabolism	A palmitic acid tracer will be given once per trial day to estimate fatty acid metabolism. Duration 1 hour.	once per study day (arm): t 45min - 105min.