Mechanisms of Insulin Resistance in Critical Illness: Role of Systemic Inflammation and GLP-1
19 september 2014 uppdaterad av: Kirsten Moller, Rigshospitalet, Denmark
The purpose of this study is to determine the role of inflammation and the insulin regulating hormone GLP-1 during critical illness.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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
Studietyp
Interventionell
Inskrivning (Faktisk)
40
Fas
- Inte tillämpbar
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
-
Copenhagen, Danmark, 2100
- Centre of Inflammation and Metabolism - Rigshospitalet 7641
-
Copenhagen, Danmark, 2400
- University of Copenhagen
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 40 år (Vuxen)
Tar emot friska volontärer
Ja
Kön som är behöriga för studier
Manlig
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Grundläggande vetenskap
- Tilldelning: Randomiserad
- Interventionsmodell: Crossover tilldelning
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Placebo-jämförare: 2C - 1
TNF and OGTT and saline
|
Normal saline (NaCl 0,9%)
1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
Oral glucose tolerance test with 75 g glucose
|
|
Aktiv komparator: 2C - 2
TNF and OGTT and GLP-1
|
1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
Oral glucose tolerance test with 75 g glucose
GLP-1 1,2pmol/kg/min i.v.
infusion for 4 hours
|
|
Placebo-jämförare: 2C - 3
TNF and IVGTT and saline
|
Normal saline (NaCl 0,9%)
1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT
|
|
Aktiv komparator: 2C - 4
TNF and IVGTT and GLP-1
|
1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
GLP-1 1,2pmol/kg/min i.v.
infusion for 4 hours
Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT
|
|
Placebo-jämförare: 2A-1
Saline infusion and OGTT
|
Normal saline (NaCl 0,9%)
Oral glucose tolerance test with 75 g glucose
|
|
Placebo-jämförare: 2A-2
Saline and IVGTT
|
Normal saline (NaCl 0,9%)
Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT
|
|
Aktiv komparator: 2A-3
TNF and OGTT
|
1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
Oral glucose tolerance test with 75 g glucose
|
|
Aktiv komparator: 2A-4
TNF and IVGTT
|
1000ng/m2 BSA/hour i.v.
infusion for 4-6 hours
Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT
|
|
Experimentell: 1C
OGTT and corresponding IVGTT
|
Oral glucose tolerance test with 75 g glucose
Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Substudy 2C (12 Healthy volunteers): GLP-1
Tidsram: 6 weeks after intervention
|
Increased plasma insulin and C-peptide (intact insulinotropic effect of GLP-1) during GLP-1 infusion in healthy volunteers.
|
6 weeks after intervention
|
|
Substudy 2A (12 Healthy volunteers): Insulin, C-peptide and incretin hormone response
Tidsram: 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)
|
6 weeks after intervention
|
|
Substudy 1C(8 patients, 8 healthy controls): Insulin, C-peptide and incretin hormone response
Tidsram: 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
|
6 weeks after intervention
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Substudy 2C (12 Healthy volunteers): Clamp
Tidsram: 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.
|
6 weeks after intervention
|
|
Substudy 2A (12 Healthy volunteers): The incretin effect
Tidsram: 6 weeks after intervention
|
The difference between the plasma insulin AUC obtained during OGTT and IVGTT (endogenous incretin effect).
|
6 weeks after intervention
|
|
Substudy 1C (8 patients, 8 healthy controls): The incretin effect
Tidsram: 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.
|
6 weeks after intervention
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Huvudutredare: Kirsten Møller, MD, Ph.D., DMSc, Centre of Inflammation and Metabolism
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
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Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 mars 2011
Primärt slutförande (Faktisk)
1 september 2014
Avslutad studie (Faktisk)
1 september 2014
Studieregistreringsdatum
Först inskickad
2 maj 2011
Först inskickad som uppfyllde QC-kriterierna
3 maj 2011
Första postat (Uppskatta)
4 maj 2011
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
22 september 2014
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
19 september 2014
Senast verifierad
1 september 2014
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- HS:H-3-2009-108
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