Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose

University of Aarhus

Status: Completed

Conditions: Hypoglycemia; Diabetes Mellitus Type I

Treatments: Drug: Insulin (Insuman Rapid); Drug: Glucose; Other: Saline

Study type: Interventional

Funder types: Other

Identifiers

NCT01919788

VEK Journal nr. M-2013-113-13 (Other Identifier)

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

Details and patient eligibility

About

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.

Enrollment: 9 patients

Sex: Male

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

• BMI > 19 and < 26
• Written Consent

Exclusion Criteria:

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Single Blind

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9 participants in 3 patient groups, including a placebo group

Control

Placebo Comparator group

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.

Treatment:

Other: Saline

Insulin

Experimental group

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

Treatment:

Drug: Insulin (Insuman Rapid)

Insulin and glucose

Experimental group

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

Treatment:

Drug: Insulin (Insuman Rapid)

Drug: Glucose