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

Brief Summary

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

Primary Outcomes

Secondary Outcomes

• Substudy 2C (12 Healthy volunteers): Clamp(6 weeks after intervention)
• Substudy 2A (12 Healthy volunteers): The incretin effect(6 weeks after intervention)
• Substudy 1C (8 patients, 8 healthy controls): The incretin effect(6 weeks after intervention)