Acute Metabolic Effects of Melatonin Treatment
Condition: Glucose Metabolism Disorders
MeSH terms: Metabolic Diseases; Glucose Metabolism Disorders
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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:

        -  Melatonin affects the substrate turn-over as evaluated by indirect calorimetry

        -  Melatonin has influence on the ability to secrete insulin as assessed by intravenous
           glucose tolerance test

        -  Melatonin affects the physiological effects of insulin as assessed by use of the
           hyperinsulinemic euglycemic clamp

        -  Genetic mutations in the melatonin receptor gene affect the treatment response to
           melatonin

      Study B:

      The investigators aim for examining if melatonin given to healthy men affects the secretion
      of the glucose-lowering gut hormone glucagon-like peptide 1 (GLP-1) and/or affect the
      glucose-lowering effects of GLP-1. Specifically, the aim is to assess whether:

        -  Melatonin affects the glucose excursions and insulin secretion during an oral glucose
           tolerance test

        -  Melatonin affects the secretion of GLP-1 during an oral glucose tolerance test

        -  Melatonin affects the incretin response as assessed by an isoglycemic glucose infusion
    

Intervention name(s): Melatonin; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Oral capsules; Oral capsules
Intervention MeSH terms: Melatonin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Melatonin; Insulin sensitivity; Insulin secretion; Incretin response