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| Name | Class |
|---|---|
| University of Copenhagen | OTHER |
| Novo Nordisk A/S | INDUSTRY |
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The purpose of this study is to determine the role of inflammation and the insulin regulating hormone GLP-1 during critical illness.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 2C - 1 | Placebo Comparator | TNF and OGTT and saline |
|
| 2C - 2 | Active Comparator | TNF and OGTT and GLP-1 |
|
| 2C - 3 | Placebo Comparator | TNF and IVGTT and saline |
|
| 2C - 4 | Active Comparator | TNF and IVGTT and GLP-1 |
|
| 2A-1 | Placebo Comparator | Saline infusion and OGTT |
|
| 2A-2 | Placebo Comparator | Saline and IVGTT |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GLP-1 | Drug | GLP-1 1,2pmol/kg/min i.v. infusion for 4 hours |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Substudy 2C (12 Healthy volunteers): GLP-1 | 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 | 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 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Substudy 2C (12 Healthy volunteers): Clamp | 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 |
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Inclusion Criteria healthy subjects:
Exclusion Criteria healthy subjects:
Inclusion Criteria critically ill patients:
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| Name | Affiliation | Role |
|---|---|---|
| Kirsten Møller, MD, Ph.D., DMSc | Centre of Inflammation and Metabolism | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre of Inflammation and Metabolism - Rigshospitalet 7641 | Copenhagen | 2100 | Denmark | |||
| University of Copenhagen |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11219223 | Background | McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin. 2001 Jan;17(1):107-24. doi: 10.1016/s0749-0704(05)70154-8. | |
| 11800522 | Background | Mizock BA. Alterations in fuel metabolism in critical illness: hyperglycaemia. Best Pract Res Clin Endocrinol Metab. 2001 Dec;15(4):533-51. doi: 10.1053/beem.2001.0168. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Nov 15, 2015 | |
| Reset | Dec 17, 2015 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Nov 15, 2015 | Dec 17, 2015 |
| ID | Term |
|---|---|
| D007003 | Hypoglycemia |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D052216 | Glucagon-Like Peptide 1 |
| D012965 | Sodium Chloride |
| D005951 | Glucose Tolerance Test |
| ID | Term |
|---|---|
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
| D006728 | Hormones |
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|
| 2A-3 | Active Comparator | TNF and OGTT |
|
| 2A-4 | Active Comparator | TNF and IVGTT |
|
| 1C | Experimental | OGTT and corresponding IVGTT |
|
| Placebo (Saline) |
| Drug |
Normal saline (NaCl 0,9%) |
|
| TNF-alfa | Drug | 1000ng/m2 BSA/hour i.v. infusion for 4-6 hours |
|
| OGTT | Other | Oral glucose tolerance test with 75 g glucose |
|
| IVGTT | Other | Intravenous glucose tolerance test with infusion of 20% glucose matching the glucose profile of the corresponding OGTT |
|
| Substudy 2A (12 Healthy volunteers): The incretin effect |
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 | 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 |
| Copenhagen |
| 2400 |
| Denmark |
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| 9628239 | Background | Willms B, Idowu K, Holst JJ, Creutzfeldt W, Nauck MA. Overnight GLP-1 normalizes fasting but not daytime plasma glucose levels in NIDDM patients. Exp Clin Endocrinol Diabetes. 1998;106(2):103-7. doi: 10.1055/s-0029-1211959. |
| 3514343 | Background | Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986 Jan;29(1):46-52. doi: 10.1007/BF02427280. |
| 8423228 | Background | Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993 Jan;91(1):301-7. doi: 10.1172/JCI116186. |
| 11246881 | Background | Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001 Mar;50(3):609-13. doi: 10.2337/diabetes.50.3.609. |
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| D013568 | Pathological Conditions, Signs and Symptoms |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D001774 | Blood Chemical Analysis |
| D019963 | Clinical Chemistry Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003940 | Diagnostic Techniques, Endocrine |
| D008919 | Investigative Techniques |