Hypoglycaemia
Conditions
Keywords
GLP-1, Inflammation, Glucose
Brief summary
The purpose of this study is to determine the role of inflammation and the insulin regulating hormone GLP-1 during critical illness.
Detailed description
Critically ill patients often exhibit hyperglycaemia. Although the cause of this hyperglycaemia is probably multifactorial, peripheral insulin resistance is a major contributor, similar to type 2 diabetes mellitus (T2D). There are several similarities between critical illness and T2D, including the presence of systemic inflammation and increased plasma free fatty acids (FFA), all of which may induce insulin resistance in healthy volunteers. In critical illness, elevated catecholamines, cortisol, growth hormone and glucagon may also contribute to insulin resistance. The degree of hyperglycaemia correlates with mortality in ICU patients. van den Berghe et al. found that IV infusion of insulin to obtain strict normoglycaemia reduced mortality as well as morbidity in critically ill surgical patients and in some medical ICU patients. However, insulin increases the risk of hypoglycaemia; this is a major obstacle to strict euglycaemia in ICU patients and may explain the inability of others to reproduce the benefits reported by van den Berghe et al. Thus, alternatives to insulin for controlling plasma glucose (PG) in ICU patients are warranted. Aim: To study the role of the incretin hormone, glucagon-like peptide (GLP)-1 for glycaemic, metabolic, hormonal and inflammatory profile in * critically ill patients in the intensive care unit (ICU) and * healthy volunteers exposed to a standardised systemic inflammation
Interventions
DRUGTNF-alfa
1000ng/m2 BSA/hour i.v. infusion for 4-6 hours
OTHEROGTT
Oral glucose tolerance test with 75 g glucose
OTHERIVGTT
Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT
DRUGGLP-1
GLP-1 1,2pmol/kg/min i.v. infusion for 4 hours
DRUGPlacebo (Saline)
Normal saline (NaCl 0,9%)
Sponsors
University of Copenhagen
Novo Nordisk A/S
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
healthy subjects: * Healthy (assessed by medical history and clinical examination) * Age 18-40years * BMI \< 30kg/m2
Exclusion criteria
healthy subjects: * Previous resection of the small intestine (not including the appendix) * presence of any inflammatory illness during the fortnight preceding the study Inclusion Criteria critically ill patients: * Age\>18 years * HbA1C\<6,5% * Admission to the ICU within the last 72 hours
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Substudy 2C (12 Healthy volunteers): GLP-1 | 6 weeks after intervention | Increased plasma insulin and C-peptide (intact insulinotropic effect of GLP-1) during GLP-1 infusion in healthy volunteers. |
| Substudy 2A (12 Healthy volunteers): Insulin, C-peptide and incretin hormone response | 6 weeks after intervention | Insulin, c-peptide and incretin hormone response to glucose stimulation during standardized systemic inflammation (TNF infusion) compared to placebo (saline infusion) |
| Substudy 1C(8 patients, 8 healthy controls): Insulin, C-peptide and incretin hormone response | 6 weeks after intervention | Insulin, c-peptide and incretin hormone response to glucose stimulation during IVGTT compared to OGTT in critically ill patients admitted to the ICU |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Substudy 2C (12 Healthy volunteers): Clamp | 6 weeks after intervention | Enhanced insulin response (AUC) and reduced difference between the AUC obtained during OGTT and IGGTT (reduced endogenous incretin effect) during an isoglycaemic intravenous glucose tolerance test (IVGTT) in healthy volunteers receiving TNF-infusion. |
| Substudy 2A (12 Healthy volunteers): The incretin effect | 6 weeks after intervention | The difference between the plasma insulin AUC obtained during OGTT and IVGTT (endogenous incretin effect). |
| Substudy 1C (8 patients, 8 healthy controls): The incretin effect | 6 weeks after intervention | The difference between the plasma insulin AUC obtained during OGTT and IVGTT (endogenous incretin effect)in non-diabetic critically ill patients admitted to the ICU. |
Countries
Denmark
Outcome results
None listed