Mechanisms of Insulin Resistance in Critical Illness: Role of Systemic Inflammation and GLP-1
- Conditions
- Hypoglycaemia
- Interventions
- Registration Number
- NCT01347801
- Lead Sponsor
- Rigshospitalet, Denmark
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description 2C - 1 OGTT TNF and OGTT and saline 2A-1 Placebo (Saline) Saline infusion and OGTT 2A-3 OGTT TNF and OGTT 2C - 2 TNF-alfa TNF and OGTT and GLP-1 2C - 2 OGTT TNF and OGTT and GLP-1 2C - 3 TNF-alfa TNF and IVGTT and saline 2A-4 TNF-alfa TNF and IVGTT 2C - 2 GLP-1 TNF and OGTT and GLP-1 2C - 4 IVGTT TNF and IVGTT and GLP-1 2C - 1 Placebo (Saline) TNF and OGTT and saline 2C - 1 TNF-alfa TNF and OGTT and saline 2C - 4 GLP-1 TNF and IVGTT and GLP-1 2A-1 OGTT Saline infusion and OGTT 2A-3 TNF-alfa TNF and OGTT 2A-4 IVGTT TNF and IVGTT 1C IVGTT OGTT and corresponding IVGTT 2C - 3 IVGTT TNF and IVGTT and saline 2C - 4 TNF-alfa TNF and IVGTT and GLP-1 1C OGTT OGTT and corresponding IVGTT 2C - 3 Placebo (Saline) TNF and IVGTT and saline 2A-2 Placebo (Saline) Saline and IVGTT 2A-2 IVGTT Saline and IVGTT
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (2)
Centre of Inflammation and Metabolism - Rigshospitalet 7641
🇩🇰Copenhagen, Denmark
University of Copenhagen
🇩🇰Copenhagen, Denmark