Acute Metabolic Effects of Melatonin Treatment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Insulin sensitivity
研究概览
简要总结
Modern living is associated with an epidemic of type 2 diabetes mellitus (T2DM). Sleep disturbances are strong independent risk factors for incident diabetes. Melatonin has been implicated in regulation of circadian rhythm and sleep, but it is also ascribed anti-oxidative properties and effects on glucose homeostasis. A potential association between melatonin and T2DM has only been addressed in few human physiological studies, but the topic has received renewed interest since genetic-epidemiological studies have pointed to a role for melatonin in the development of the disease. In the current study, the investigators wish to examine whether treatment with synthetic melatonin induces physiological changes that affect the risk of developing type 2 diabetes. Two studies of the physiological effects of melatonin are included in the present protocol. In study A, the investigators will examine the acute effects of Melatonin on insulin secretion and insulin sensitivity using a Botnia clamp and in study B the investigators will examine the potential effects of Melatonin on the incretin response.
详细描述
Modern living is associated with an epidemic of type 2 diabetes mellitus (T2DM). Sleep disturbances such as insomnia and frequent awakenings are strong independent risk factors for incident diabetes with a magnitude of effect comparable to a family history of diabetes. Melatonin has been implicated in regulation of circadian rhythm and sleep, but it is also ascribed anti-oxidative properties and effects on glucose homeostasis. In pancreatic islets melatonin have dual effects depending on which signaling pathway is activated by receptor binding, thus both inhibitory and stimulatory effects on insulin secretion have been reported. The effect of melatonin on the secretion of gut hormones such as glucagon-like peptide 1 (GLP-1) and influence of melatonin on beta cell sensitivity to gut hormones is largely unknown, but the presence of the melatonin receptor in the gut suggests that it may have a role. A potential association between melatonin and T2DM has only been addressed in few human physiological studies, but the topic has received renewed interest since genetic-epidemiological studies have pointed to a role for melatonin in the development of the disease. Genetic mutations in the melatonin receptor which is predicted to change the physiological effects of melatonin have been found to increase the risk for T2DM. Additionally, low endogenous melatonin production has been linked to T2DM risk.
The aim of the present study is to examine whether treatment with synthetic melatonin induces physiological changes that affect the risk of developing type 2 diabetes.
Two studies of the physiological effects of melatonin are included in the present protocol:
Study A:
In order to study the acute effects of melatonin administration in healthy men, the investigators aim for assessing whether:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age 20-40 years
- •BMI between 22-30 kg/m2
- •Written consent prior to study participation
排除标准
- •Diabetes or impaired glucose tolerance (fasting p-glucose ≥ 6.1mmol/L)
- •Daily use of a prescription drug
- •Shift work within the last year
- •Travel across >2 time zones in the past three months
- •Use of melatonin on a regular basis within the last year
- •Severe illness
- •High performance athletes
- •Daily tobacco smoking
- •Previous diagnosis of a sleep disorder
- •Present or earlier alcohol or drug abuse
- •Unable to give informed consent
- •Allergy towards melatonin
研究组 & 干预措施
Melatonin
Four capsules of Melatonin 10 mg is administered orally every hours for four hours during the study day.
干预措施: Melatonin (Drug)
Placebo
Four capsules of placebo is administered orally every hours for four hours during the study day.
干预措施: Placebo (Other)
结局指标
主要结局
Insulin sensitivity
时间窗: 2 hours (from t= 105 to 225 minutes)
Insulin sensitivity is assessed by a hyperinsulinemic euglycemic clamp, unit: mg/kg/min
Insulin secretion
时间窗: 1 hour (from t = 45 to 105 minutes)
Insulin secretion is assessed by an intravenous glucose tolerance test, unit: pmol/L (insulin)
Incretin response
时间窗: 4 hours (from t = 0 to 240 minutes)
The incretin response is assessed by the difference in incretin hormones between an oral glucose tolerance test and an isoglycemic intravenous glucose infusion, unit: pmol/L (GIP, GLP-1)
次要结局
- Inflammatory markers(Baseline t = -60 minutes and at t = 45 minutes)
- Substrate oxidation(From t=15 minutes to 45 minutes and from t=195 minutes to 225 minutes)
- Hormones(Baseline t = -60 minutes and at t = 45 minutes)