Characterizing the Incretin Effect of Amino Acids (AA) and Defining the Effect of GLP-1 on Muscle Microvascular Blood Flow and Muscle Protein and Glucose Metabolism in Older Age.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Muscle protein and glucose metabolism
研究概览
简要总结
This study has two protocols the aims of which are:
- To identify age-related effects of AA on incretin secretion and whether and to what extent AA exhibit a true incretin effect (gut- mediated increases in plasma insulin) in younger individuals. (Protocol 1)
- To define the extra-pancreatic ''novel'', insulin independent effects of glucagon like peptide-1 (GLP-1) on postprandial muscle protein and glucose metabolism and microvascular blood flow. (Protocol 2)
详细描述
Protocol 1:
This will explore the first aim. 8 Healthy younger volunteers will be recruited to under go 3 arms cross over studies. Interventions will include oral and intravenous amino acids, in addition to intravenous GLP-1 and glucose dependent insulinotropic polypeptide (GIP).
8 older subjects also will be recruited for comparison of the response of GI hormones to amino acids oral feed between young and older men.
Therefore the total number will be recruited to perform this protocol is 16.
Post intervention in all visits, measurements will be taken for:
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •For protocol 1: i. Aged between 18-40 or 65-75 years ii. A body mass index (BMI) >18 and <28 kg/m2
- •For Protocol 2: i. Age 65-75 years ii. A body mass index (BMI) >18 and <28 kg/m2
排除标准
- •For protocol 1:
- •i. A BMI < 18 or > 28 kg·m2 ii. Active cardiovascular disease: uncontrolled hypertension (BP > 160/100), angina, heart failure (class III/IV), arrhythmia, right to left cardiac shunt or recent cardiac event iii. Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial) iv. Respiratory disease including pulmonary hypertension, chronic obstructive pulmonary disease (COPD), asthma or an forced expiratory volume in 1 minute (FEV1) less than 1.5 litre.
- •v. Metabolic disease: hyper and hypo-parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, types 1 or 2 diabetes vi. Active inflammatory bowel or renal disease vii. Malignancy viii. Recent steroid treatment (within 6 month), or hormone replacement therapy ix. Clotting dysfunction x. Musculoskeletal or neurological disorders xi. Family history of early (<55y) death from cardiovascular disease
- •For protocol 2:
- •Same as protocol 1 in addition to:
- •i. Overt muscle wasting i.e. muscle mass is more than 1 standard deviation below normal muscle or fat-free mass for age.
- •ii. Taking beta-adrenergic blocking agents or non-steroidal anti-inflammatory drugs iii. Known sensitivity to SONOVUE or any other drug used in the study. iv. Subject deemed unsuitable for femoral cannulation at screening visit.
研究组 & 干预措施
Post absorptive insulin without GLP-1
Subjects with receive post absorptive insulin concentrations while measures of muscle metabolism and microvascular blood flow are taken through the acute study hours.
The intervention in this group is Insulin Actrapid to achieve post absorptive insulin levels and glucose infusion to achieve postprandial glucose levels of 7.0-7.5 mmol/L . This will form base line measurement for the next arm which will receive GLP-1 in addition.
干预措施: Insulin Actrapid (Drug)
Postabsorptive insulin with GLP-1
Subjects will receive post absorptive insulin concentrations with GLP-1 while measures of muscle metabolism and microvascular blood flow are taken through the acute study hours. This arm will cross over with the previous arm.
The intervention in this group is in the form of GLP-1, Insulin Actrapid to achieve post absorptive insulin levels and glucose infusion to achieve postprandial glucose levels of 7.0-7.5 mmol/L .
干预措施: Insulin Actrapid (Drug)
Postprandial insulin without GLP-1
Subjects will receive postprandial insulin concentrations without GLP-1 while measures of muscle metabolism and microvascular blood flow are taken through the acute study hours.
The intervention in this group is Insulin Actrapid to achieve postprandial insulin levels and glucose infusion to achieve postprandial glucose levels of 7.0-7.5 mmol/L . This will form base line measurement for the next arm which will receive GLP-1 in addition
干预措施: Insulin Actrapid (Drug)
IV amino acids, GLP-1, GIP -Young
Gut hormones will be measured after intravenous amino acid infusion delivering iso equivalent amount of amino acids, GLP-1, GIP in young persons.
The intervention in this group: Intravenous amino acids iso-equivalent to oral 15 g mixed essential amino acids, GLP-1 infusion and GIP infusion
干预措施: Intravenous amino acids (Drug)
Postprandial insulin with GLP-1
Subjects with receive postprandial insulin concentrations with GLP-1 while measures of muscle metabolism and microvascular blood flow are taken through the acute study hours. This arm will cross over with the previous arm.
The intervention in this group is in the form of GLP-1, Insulin Actrapid to achieve postprandial insulin levels and glucose infusion to achieve postprandial glucose levels of 7.0-7.5 mmol/L .
干预措施: Insulin Actrapid (Drug)
Oral amino acids-Young
Gut hormones will be measured post oral drink containing 15 g of amino acids in young persons. This will cross over with the following 2 arms.
The intervention here is: 15g of mixed essential amino acid drink.
干预措施: Oral amino acids (Dietary Supplement)
Intravenous (IV) amino acids- Young
Gut hormones will be measured after intravenous amino acid infusion delivering iso equivalent amount of amino acids in young persons.
The intervention in this group: Intravenous amino acids delivering iso-equivalent amount of 15g mixed essential amino acids
干预措施: Intravenous amino acids (Drug)
IV amino acids, GLP-1, GIP -Young
Gut hormones will be measured after intravenous amino acid infusion delivering iso equivalent amount of amino acids, GLP-1, GIP in young persons.
The intervention in this group: Intravenous amino acids iso-equivalent to oral 15 g mixed essential amino acids, GLP-1 infusion and GIP infusion
干预措施: GIP (Drug)
Oral amino acids- Older
Gut hormones will be measured post oral drink containing 15 g of mixed essential amino acids in older persons.
The intervention in this arm: 15 gram of oral mixed essential amino acid drink
干预措施: Oral amino acids (Dietary Supplement)
Postabsorptive insulin with GLP-1
Subjects will receive post absorptive insulin concentrations with GLP-1 while measures of muscle metabolism and microvascular blood flow are taken through the acute study hours. This arm will cross over with the previous arm.
The intervention in this group is in the form of GLP-1, Insulin Actrapid to achieve post absorptive insulin levels and glucose infusion to achieve postprandial glucose levels of 7.0-7.5 mmol/L .
干预措施: GLP-1 (Drug)
IV amino acids, GLP-1, GIP -Young
Gut hormones will be measured after intravenous amino acid infusion delivering iso equivalent amount of amino acids, GLP-1, GIP in young persons.
The intervention in this group: Intravenous amino acids iso-equivalent to oral 15 g mixed essential amino acids, GLP-1 infusion and GIP infusion
干预措施: GLP-1 (Drug)
Postprandial insulin with GLP-1
Subjects with receive postprandial insulin concentrations with GLP-1 while measures of muscle metabolism and microvascular blood flow are taken through the acute study hours. This arm will cross over with the previous arm.
The intervention in this group is in the form of GLP-1, Insulin Actrapid to achieve postprandial insulin levels and glucose infusion to achieve postprandial glucose levels of 7.0-7.5 mmol/L .
干预措施: GLP-1 (Drug)
结局指标
主要结局
Muscle protein and glucose metabolism
时间窗: 12 months
Assessed from muscle biopsies taken for measurement of protein synthesis and breakdown and glucose uptake.
次要结局
- Leg Microvascular blood flow(12 months)
- Leg Macrovascular blood flow(12 months)
- Gut hormones secretion in response to amino acids in young and older people(12 months)
- Insulin secretion in response to oral and intravenous amino acids to assess their ability to exert incretin effect.(12 months)