Clinical trial NCT01919788: Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose
Official title: Intracellular Counter-regulatory Mechanisms Following Low Blood Glucose
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus Type I
Hypoglycemia
Keywords: Diabetes Mellitus Type I
Hypoglycemia
Counter-regulatory mechanisms
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2013-08-09
Enrollment: 9
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: * BMI \> 19 and \< 26
* Written Consent

Exclusion Criteria:

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

Primary outcomes:
measure: 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.
timeFrame: 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 outcomes:
measure: Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies.
timeFrame: Biopsies obtained on each study day (arm). Muscle biopsies: time (t)= -30min, t= 30min and t= 75min. Fat biopsies: t= 30min and t= 75min
measure: Metabolism.
timeFrame: measured twice on each study day (arm) at t= -30-0 min. and t= 50-80 min.
measure: Ghrelin
timeFrame: 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)
measure: Metabolism
timeFrame: once per study day (arm): t 45min - 105min.
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Institute of Clinical Medicine
state: Aarhus C
Study officials:
affiliation: Aarhus University / Aarhus University Hospital
name: Niels Møller, MD
role: STUDY_CHAIR
affiliation: Aarhus University / Aarhus University Hospital
name: Thomas Voss, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.