LEAP2 on Postprandial Glucose Metabolism and Food Intake in Obese Males
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Food intake, kilojoules per kilogram body weight
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Caucasian men
- •Age between 18 and 25 years
- •Body mass index between 30-50 kg/m2
- •Informed consent
排除标准
- •Anaemia (haemoglobin below normal range)
- •Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary and/or gastrointestinal disorder(s)
- •Nephropathy (serum creatinine above normal range and/or albuminuria)
- •Allergy or intolerance to ingredients included in the standardised meals
- •First-degree relatives with diabetes and/or glycated haemoglobin (HbA1c) >48 mmol/mol
- •Regular tobacco smoking or use of other nicotine-containing products
- •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
研究组 & 干预措施
Placebo
IV infusion of saline, approximately 5.5 hours
干预措施: LEAP-2 Protein, Human (Drug)
Liver-enriched antimicrobial peptide 2
IV infusion of LEAP2, approximately 5.5 hours
干预措施: LEAP-2 Protein, Human (Drug)
结局指标
主要结局
Food intake, kilojoules per kilogram body weight
时间窗: 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.
Food intake, kilojoules
时间窗: 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.
次要结局
- Changes in resting energy expenditure (REE)(-35 to 320 minutes)
- Triglyceride responses(-35 to 320 minutes)
- Cholesterol responses(-35 to 320 minutes)
- Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration(-35 to 320 minutes)
- Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones(-35 to 320 minutes)
- VAS, appetite(-35 to 320 minutes)
- VAS, satiety(-35 to 320 minutes)
- VAS, hunger(-35 to 320 minutes)
- VAS, thirst(-35 to 320 minutes)
- Alterations in gastric emptying(-35 to 320 minutes)
- Free fatty acid responses(-35 to 320 minutes)
研究者
Filip Krag Knop
Professor, MD, PhD
University Hospital, Gentofte, Copenhagen