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Type 2 diabetes mellitus, T2D is a disease characterized by an immense growing prevalence world wide with an increased risk of myocardial infarction and stroke. GLP-1 has convincing effects on the high glucose levels in type 2 diabetic patients and is well tolerated. New animal studies indicate a protective effect of GLP-1 in the brain and the heart. The mechanism behind this is yet not known.
The study hypothesis is that GLP-1 will stimulate glucose-uptake in the brain and heart independent of insulin and thereby exert its protective effects.
Type 2 diabetes mellitus, T2D is a disease characterized by an immense growing prevalence world wide. T2D is associated with a three-fold increase in cardiovascular complications (myocardial infarction and stroke) leading to significantly higher morbidity and mortality in this group of patients. The prospective British Diabetes Study (UKPDS) showed that neither diet alone nor the pharmaceutical treatment utilized (Sulphonylurea, Metformin, Insulin) were able to reduce these macrovascular complications. GLP-1 (glucagon-like-peptide-1)is an incretin with convincing effects on glycaemia in type 2 diabetic patients with little or no risk of hypoglycaemia. New research in animal models has shown a potential protective effect in the brain and heart in association with ischaemic damage. The mechanism behind this protective effect is not known.
The effect of native GLP-1 on glucose uptake in the brain and heart will by visualized by fluoro-deoxy-glucose FDG-PET-scan during normoglycaemia in healthy young men. At the same time a pancreatic/pituitary clamp will be performed. The hypothesis is that GLP-1 directly will stimulate glucose uptake independent of the pancreatic hormones and through this mechanism exert its neuro- and cardioprotective actions.
Comparisons: FDG-uptake in the brain and heart with GLP-1 infusion compared to placebo.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| glucagon-like-peptide-1 | Drug | Dose: 1.2pmol/kg/min for 6 hours |
| Measure | Description | Time Frame |
|---|---|---|
| FDG-uptake in the brain and heart visualized by Positron emission tomography with and without GLP-1 | After 4 hours of GLP-infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Laboratory values (insulin secretion and counter-regulatory hormones) | During 7 hours of clamp and GLP-1/placebo infusion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ole Schmitz, MD,professor | Department of pharmacology, Aarhus university | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of pharmacology, Aarhus university | Aarhus | 8000 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12925848 | Background | During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003 Sep;9(9):1173-9. doi: 10.1038/nm919. Epub 2003 Aug 17. | |
| 14981009 | Background | Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, Shannon RP. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004 Mar 2;109(8):962-5. doi: 10.1161/01.CIR.0000120505.91348.58. Epub 2004 Feb 23. |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D020521 | Stroke |
| D009203 | Myocardial Infarction |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D052216 | Glucagon-Like Peptide 1 |
| ID | Term |
|---|---|
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
| D006728 | Hormones |
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| 15655703 | Background | Holst JJ. On the physiology of GIP and GLP-1. Horm Metab Res. 2004 Nov-Dec;36(11-12):747-54. doi: 10.1055/s-2004-826158. |
| 12183643 | Background | Perry T, Haughey NJ, Mattson MP, Egan JM, Greig NH. Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. J Pharmacol Exp Ther. 2002 Sep;302(3):881-8. doi: 10.1124/jpet.102.037481. |
| 15883751 | Background | Bose AK, Mocanu MM, Carr RD, Yellon DM. Glucagon like peptide-1 is protective against myocardial ischemia/reperfusion injury when given either as a preconditioning mimetic or at reperfusion in an isolated rat heart model. Cardiovasc Drugs Ther. 2005 Jan;19(1):9-11. doi: 10.1007/s10557-005-6892-4. No abstract available. |
| 24400077 | Derived | Gejl M, Lerche S, Mengel A, Moller N, Bibby BM, Smidt K, Brock B, Sondergaard H, Botker HE, Gjedde A, Holst JJ, Hansen SB, Rungby J. Influence of GLP-1 on myocardial glucose metabolism in healthy men during normo- or hypoglycemia. PLoS One. 2014 Jan 6;9(1):e83758. doi: 10.1371/journal.pone.0083758. eCollection 2014. |
| D004700 | Endocrine System Diseases |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |