Diabetes Mellitus Type I, Hypoglycemia
Conditions
Keywords
Diabetes Mellitus Type I, Hypoglycemia, Counter-regulatory mechanisms
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.
Interventions
DRUGInsulin (Insuman Rapid)
DRUGGlucose
OTHERSaline
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* BMI \> 19 and \< 26 * Written Consent
Exclusion criteria
* Epilepsy * Cardiac arrythmia * Ischemic heart disease * Other medical illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Change in phosphorylation of target proteins and mRNA expression of target genes assessed with western blotting technique. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Assessed by Western blotting. |
| Metabolism. | measured twice on each study day (arm) at t= -30-0 min. and t= 50-80 min. | Assessment of glucose metabolism by forearm pletysmography and heated hand technique (duration of pletysmography = 30 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. | A palmitic acid tracer will be given once per trial day to estimate fatty acid metabolism. Duration 1 hour. |
Countries
Denmark
Outcome results
None listed