Mechanisms of Insulin Resistance in Critical Illness: Role of Systemic Inflammation and GLP-1

Rigshospitalet

Status: Completed

Conditions: Hypoglycaemia

Treatments: Drug: GLP-1; Other: IVGTT; Drug: Placebo (Saline); Drug: TNF-alfa; Other: OGTT

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01347801

HS:H-3-2009-108

Details and patient eligibility

About

The purpose of this study is to determine the role of inflammation and the insulin regulating hormone GLP-1 during critical illness.

Full 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

Enrollment: 40 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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40 participants in 9 patient groups, including a placebo group

2C - 1

Placebo Comparator group

Description:

TNF and OGTT and saline

Treatment:

Drug: TNF-alfa

Other: OGTT

Drug: Placebo (Saline)

2C - 2

Active Comparator group

Description:

TNF and OGTT and GLP-1

Treatment:

Drug: TNF-alfa

Other: OGTT

Drug: GLP-1

2C - 3

Placebo Comparator group

Description:

TNF and IVGTT and saline

Treatment:

Drug: TNF-alfa

Other: IVGTT

Drug: Placebo (Saline)

2C - 4

Active Comparator group

Description:

TNF and IVGTT and GLP-1

Treatment:

Drug: TNF-alfa

Other: IVGTT

Drug: GLP-1

2A-1

Placebo Comparator group

Description:

Saline infusion and OGTT

Treatment:

Other: OGTT

Drug: Placebo (Saline)

2A-2

Placebo Comparator group

Description:

Saline and IVGTT

Treatment:

Other: IVGTT

Drug: Placebo (Saline)

2A-3

Active Comparator group

Description:

TNF and OGTT

Treatment:

Drug: TNF-alfa

Other: OGTT

2A-4

Active Comparator group

Description:

TNF and IVGTT

Treatment:

Drug: TNF-alfa

Other: IVGTT

1C

Experimental group

Description:

OGTT and corresponding IVGTT

Treatment:

Other: IVGTT

Other: OGTT