Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose

Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose

Sponsors

Lead sponsor: University of Aarhus

Source University of Aarhus
Brief 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.

Overall Status Completed
Start Date August 2013
Completion Date April 2014
Primary Completion Date April 2014
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
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. 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 Outcome
Measure Time Frame
Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies. Biopsies obtained on each study day (arm). Muscle biopsies: time (t)= -30min, t= 30min and t= 75min. Fat biopsies: t= 30min and t= 75min
Metabolism. measured twice on each study day (arm) at t= -30-0 min. and t= 50-80 min.
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)
Metabolism once per study day (arm): t 45min - 105min.
Enrollment 9
Condition
Intervention

Intervention type: Drug

Intervention name: Insulin (Insuman Rapid)

Intervention type: Drug

Intervention name: Glucose

Arm group label: Insulin and glucose

Intervention type: Other

Intervention name: Saline

Arm group label: Control

Eligibility

Criteria:

- BMI > 19 and < 26

- Written Consent

Exclusion Criteria:

- Epilepsy

- Cardiac arrythmia

- Ischemic heart disease

- Other medical illness

Gender: Male

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Location
facility Institute of Clinical Medicine
Location Countries

Denmark

Verification Date

September 2019

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: University of Aarhus

Investigator full name: Thomas Schmidt Voss

Investigator title: MD

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Arm group label: Control

Arm group type: Placebo Comparator

Description: 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.

Arm group label: Insulin

Arm group type: Experimental

Description: 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

Arm group label: Insulin and glucose

Arm group type: Experimental

Description: 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

Study Design Info

Allocation: Randomized

Intervention model: Factorial Assignment

Primary purpose: Basic Science

Masking: Single (Participant)

Source: ClinicalTrials.gov