LEAP2-OBCT: LEAP2 on Postprandial Glucose Metabolism and Food Intake n Obese Males
Study Details
Study Description
Brief Summary
The study aims to delineate the effects of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) on postprandial glucose metabolism and food intake in obese volunteers. The overall objective is to investigate the physiological importance of LEAP-2 in obese subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
In a recent study, the molecular phenotype of enteroendocrine cells in the small intestine before and after Roux-en-Y Gastric Bypass (RYGB) surgery in obese individuals was examined. Enteroendocrine cells were identified and isolated from intestinal biopsies and analysed for differentially expressed genes by Illumina High Throughput RNA-sequencing. It was discovered that the gene encoding liver-enriched antimicrobial peptide 2 (LEAP-2), a naturally occurring peptide in humans, was significantly upregulated compared to baseline expression. Interestingly, LEAP-2 was recently shown to antagonize ghrelin function in response to feeding in mice. Moreover, the mature murine LEAP-2 peptide is identical in mice and humans. Thus, LEAP-2 has been identified as an endogenous peptide that may be able to alter feeding behaviour and maintenance of glucose levels during calorie restriction. Our group recently found a 12 % relative reduction in ad libitum food intake and reduced postprandial glucose excursions.
The present study hypothesis is that LEAP-2 alters postprandial glucose metabolism and decreases appetite as well as food intake in relation to a liquid mixed meal and a standardised ad libitum meal compared with saline (placebo) in obese subjects.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo IV infusion of saline, approximately 5.5 hours |
Drug: LEAP-2 Protein, Human
Intravenous infusion, mixed meal test, ad libitum meal test
|
| Experimental: Liver-enriched antimicrobial peptide 2 IV infusion of LEAP2, approximately 5.5 hours |
Drug: LEAP-2 Protein, Human
Intravenous infusion, mixed meal test, ad libitum meal test
|
Outcome Measures
Primary Outcome Measures
- Food intake, kilojoules [290 to 320 minutes]
Difference in food intake during an ad libitum meal. Food intake is examined as kilojoules of food eaten during the ad libitum meal.
- Food intake, kilojoules per kilogram body weight [290 to 320 minutes]
Difference in food intake during an ad libitum meal. Food intake is examined as kilojoules per kilogram body weight of food eaten during the ad libitum meal.
Secondary Outcome Measures
- VAS, appetite [-35 to 320 minutes]
Visual analogue scales (VASs) assessing appetite (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)
- VAS, satiety [-35 to 320 minutes]
Visual analogue scales (VASs) assessing satiety sensations (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)
- VAS, hunger [-35 to 320 minutes]
Visual analogue scales (VASs) assessing hunger sensations (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)
- VAS, thirst [-35 to 320 minutes]
Visual analogue scales (VASs) assessing thirst (from 0 to 9,5 cm on a scale = from minimum to maximum sensation)
- Alterations in gastric emptying [-35 to 320 minutes]
Paracetamol concentration in plasma after intake of 1.5 g paracetamol
- Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration [-35 to 320 minutes]
Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration
- Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones [-35 to 320 minutes]
Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones
- Changes in resting energy expenditure (REE) [-35 to 320 minutes]
Changes in resting energy expenditure (REE) measured by indirect calorimetry
- Triglyceride responses [-35 to 320 minutes]
Plasma triglyceride
- Cholesterol responses [-35 to 320 minutes]
Plasma Cholesterol
- Free fatty acid responses [-35 to 320 minutes]
Plasma Free fatty acid
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Caucasian men
-
Age between 18 and 25 years
-
Body mass index between 30-50 kg/m2
-
Informed consent
Exclusion Criteria:
-
Anaemia (haemoglobin below normal range)
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Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary and/or gastrointestinal disorder(s)
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Nephropathy (serum creatinine above normal range and/or albuminuria)
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Allergy or intolerance to ingredients included in the standardised meals
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First-degree relatives with diabetes and/or glycated haemoglobin (HbA1c) >48 mmol/mol
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Regular tobacco smoking or use of other nicotine-containing products
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Any ongoing medication that the investigator evaluates would interfere with trial participation.
-
Any physical or psychological condition that the investigator evaluates would interfere with trial participation including any acute or chronic illnesses
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Center for Clinical Metabolic Research, Gentofte Hospital | Hellerup | Capital Region | Denmark | 2900 |
Sponsors and Collaborators
- University Hospital, Gentofte, Copenhagen
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-19038628