Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose

NCT ID: NCT01919788

Last Updated: 2019-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2014-04-30

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.

Conditions

Diabetes Mellitus Type I; Hypoglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: OTHER

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

Group Type: EXPERIMENTAL

Insulin (Insuman Rapid)

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Insulin (Insuman Rapid)

Intervention Type: DRUG

Glucose

Intervention Type: DRUG

Interventions

Insulin (Insuman Rapid)

Intervention Type: DRUG

Glucose

Intervention Type: DRUG

Saline

Intervention Type: OTHER

Eligibility Criteria

Exclusion Criteria

• Epilepsy
• Cardiac arrythmia
• Ischemic heart disease
• Other medical illness

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Thomas Schmidt Voss

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Niels Møller, MD

Role: STUDY_CHAIR

Aarhus University / Aarhus University Hospital

Thomas Voss, MD

Role: PRINCIPAL_INVESTIGATOR

Aarhus University / Aarhus University Hospital

Locations

Institute of Clinical Medicine

Aarhus, Aarhus C, Denmark

Countries

Denmark

References

Voss TS, Vendelbo MH, Kampmann U, Hingst JR, Wojtaszewski JFP, Svart MV, Moller N, Jessen N. Acute Hypoglycemia in Healthy Humans Impairs Insulin-Stimulated Glucose Uptake and Glycogen Synthase in Skeletal Muscle: A Randomized Clinical Study. Diabetes. 2017 Sep;66(9):2483-2494. doi: 10.2337/db16-1559. Epub 2017 Jun 8.

Reference Type: DERIVED

PMID: 28596236 (View on PubMed)

Voss TS, Vendelbo MH, Kampmann U, Pedersen SB, Nielsen TS, Johannsen M, Svart MV, Jessen N, Moller 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. doi: 10.1007/s00125-016-4126-x. Epub 2016 Oct 12.

Reference Type: DERIVED

PMID: 27734104 (View on PubMed)

Other Identifiers

VEK Journal nr. M-2013-113-13

Identifier Type: OTHER

Identifier Source: secondary_id

VEK journal nr.: M-2013-113-13

Identifier Type: -

Identifier Source: org_study_id