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We aim to delineate the effects of separate and combined infusion of GIP and GLP-1 on food intake, appetite, bone health and fat metabolism in overweight/obese subjects.
The gut-derived incretin glucagon-like peptide-1 (GLP-1) is a potent regulator of gastric emptying, appetite and food intake in humans whereas its sister incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), does not seem to have independent effects on these variables in humans. Interestingly, recent data from rodents have shown that concomitant activation of the GIP and the GLP-1 receptor may potentiate the satiety-promoting and body weight-reducing effects of GLP-1. Also, evidence suggests that GIP may be an important mediator of bone remodelling and lipid deposition. The effect of simultaneous activation of the GIP and GLP-1 receptors on appetite, food intake, fat metabolism and bone health has not been thoroughly examined in humans. The aim of this study is to delineate the effects of GIP/GLP-1 receptor co-activation on food intake, mechanisms regulating food intake, fat and bone metabolism in obese subjects.
Material and methods:
The investigators plan to include 18 obese/overweight men without diabetes. The primary endpoint of the study is food intake during continuous intravenous infusions of saline (placebo), GIP, GLP-1 and GIP+GLP-1, respectively. Secondary endpoints includes resting energy expenditure (measured by indirect calorimetry), appetite, satiety and hunger assessments (measured by visual analogue scales), plasma insulin, C-peptide and glucagon secretion, plasma triglycerides, cholesterols, and free fatty acid responses and changes in plasma bone turnover markers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IIGI+GIP | Active Comparator | 4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions |
|
| IIGI+GLP-1 | Active Comparator | 4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions |
|
| IIGI+NaCl (placebo) | Placebo Comparator | 4 hour i.v. NaCl (placebo) during isoglycemic conditions |
|
| IIGI+GIP+GLP-1 | Active Comparator | 4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 |
|
| 50 g OGTT | Other |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IIGI+GIP | Other | Glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemia |
|
| Measure | Description | Time Frame |
|---|---|---|
| food intake | How much does the participant eat of from the ad libitum meal, measured in gram | 250-280 min |
| Measure | Description | Time Frame |
|---|---|---|
| hunger | feeling of hunger measured on a visual analogue scale | measured at time 0, 30, 60, 90, 120, 180, 210, 240 min |
| satiety | feeling of satiety measured on a visual analogue scale |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Natasha C Bergmann, MD | Center for Diabetesresearch, Gentofte Hospital, University of Copenhagen, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Diabetesresearch, Gentofte hospital | Hellerup | 2900 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24174327 | Background | Finan B, Ma T, Ottaway N, Muller TD, Habegger KM, Heppner KM, Kirchner H, Holland J, Hembree J, Raver C, Lockie SH, Smiley DL, Gelfanov V, Yang B, Hofmann S, Bruemmer D, Drucker DJ, Pfluger PT, Perez-Tilve D, Gidda J, Vignati L, Zhang L, Hauptman JB, Lau M, Brecheisen M, Uhles S, Riboulet W, Hainaut E, Sebokova E, Conde-Knape K, Konkar A, DiMarchi RD, Tschop MH. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci Transl Med. 2013 Oct 30;5(209):209ra151. doi: 10.1126/scitranslmed.3007218. | |
| 23684623 |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D005951 | Glucose Tolerance Test |
| ID | Term |
|---|---|
| D001774 | Blood Chemical Analysis |
| D019963 | Clinical Chemistry Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
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50 g oral glucose tolerance test (OGTT)
|
| IIGI+GLP-1 | Other | glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemia |
|
| IIGI+NaCl (placebo) | Other | i.v. NaCl during isoglycemia |
|
| OGTT | Other | 50 g oral glucose tolerance test |
|
| IIGI+GIP+GLP-1 | Other | i.v infusion of GIP and GLP-1 (4 + 1 pmol/kg/min) during isoglycemia |
|
| measured at time 0, 30, 60, 90, 120, 180, 210, 240 min |
| Fullness | feeling of fullness measured on a visual analogue scale | measured at time 0, 30, 60, 90, 120, 180, 210, 240 min |
| Prospective food consumption | Prospective food consumption measured on a visual analogue scale | measured at time 0, 30, 60, 90, 120, 180, 210, 240 min |
| resting energy expenditure (REE) | changes in REE measured by a ventilated hood 15 minutes at baseline and 15 minutes at time point 210 min. | -15 to 0 min. and 210 to 225 min. |
| Insulin | changes in insulin measured in serum | -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min |
| C-peptide level | changes in C-peptide level measured in serum | -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min |
| glucagon levels | changes in glucagon levels measured in plasma | -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min |
| Cholesterol and FFA | changes in cholesterol (TAG, Total cholesterol and free fatty acid measured in plasma) | -30, 0, 30, 60, 90, 120, 180, 240 min |
| C-terminal cross-linked telopeptide of bone collagen (CTX) | changes in level of CTX measured in plasma | -30, 0, 30, 60, 90, 120, 180, 240 min |
| procollagen type 1 N-terminal propeptide (P1NP) | changes in level of P1NP measured in plasma | -30, 0, 30, 60, 90, 120, 180, 240 min |
| Background |
| Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013 Jun 4;17(6):819-837. doi: 10.1016/j.cmet.2013.04.008. Epub 2013 May 16. |
| 9449682 | Background | Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest. 1998 Feb 1;101(3):515-20. doi: 10.1172/JCI990. |
| 25144635 | Background | Nissen A, Christensen M, Knop FK, Vilsboll T, Holst JJ, Hartmann B. Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans. J Clin Endocrinol Metab. 2014 Nov;99(11):E2325-9. doi: 10.1210/jc.2014-2547. Epub 2014 Aug 21. |
| 30848791 | Derived | Bergmann NC, Lund A, Gasbjerg LS, Jorgensen NR, Jessen L, Hartmann B, Holst JJ, Christensen MB, Vilsboll T, Knop FK. Separate and Combined Effects of GIP and GLP-1 Infusions on Bone Metabolism in Overweight Men Without Diabetes. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2953-2960. doi: 10.1210/jc.2019-00008. |
| 30683945 | Derived | Bergmann NC, Lund A, Gasbjerg LS, Meessen ECE, Andersen MM, Bergmann S, Hartmann B, Holst JJ, Jessen L, Christensen MB, Vilsboll T, Knop FK. Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study. Diabetologia. 2019 Apr;62(4):665-675. doi: 10.1007/s00125-018-4810-0. Epub 2019 Jan 25. |
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D003933 | Diagnosis |
| D003940 | Diagnostic Techniques, Endocrine |
| D008919 | Investigative Techniques |