Influence of Moderate Exercise on Blood Glucose in Type 2 Diabetics and Healthy Controls
Condition: Type 2 Diabetes and Exercise
MeSH terms: Diabetes Mellitus, Type 2
Study type: Observational

Summary: 
      Project description

      Research project title:

      Influence of moderate exercise on blood glucose in type 2 diabetics and healthy controls.

      Project description and objective

      Obesity is so widespread in Denmark that 47% of the population is classed as overweight
      (BMI>=25) and around 13% of the population is classed as obese (BMI>=30).

      The strong correlation between obesity and type 2 diabetes (at least 2/3 of type 2 diabetics
      are overweight) has led to many studies which look at different forms of exercise for this
      group, because weight loss may improve the diabetes and even defer the onset of the disorder
      and in doing so lower complications and increase long term survival.

      For people who do not have type 2 diabetes, the work-induced increased sympathetic activity
      will lead to suppressed insulin secretion and increased glucagon secretion. This increases
      the endogenous glucose production from the liver and thus maintains a normal concentration of
      blood sugar in a physical training situation where the demand for glucose has increased.

      The theory behind the project is that the mechanisms that help to increase glucose production
      in the liver during physical activity are weaker in type 2 diabetics, which can cause
      hypoglycaemia during and after physical exercise. In other words, we want to study the
      liver's sensitivity to stimulus from physical work by patients with type 2 diabetes and in
      relevant healthy control subjects.

      Previous studies have indicated that this type of mechanism is not intact in type 2
      diabetics; because the level of insulin does not fall as expected during or after physical
      training. However, there are no existing studies that measure the liver's glucose secretion
      using stable isotopes during prolonged moderate physical work. Measuring this will help to
      clarify our understanding of glucose homeostasis in type 2 diabetics.

      This study is very relevant, because it may be expected that the preferred form of physical
      exercise of an overweight type 2 diabetic can be of moderate intensity and previous studies
      also show that this form of physical exercise delivers health gains in terms of an
      improvement in insulin sensitivity and a reduction in the level of insulin.

      The objective of this study is to determine if the level of blood glucose stays constant
      before, during and after physical training and to examine the liver's ability to secret
      glucose accordingly.
    

Detailed description: 
      Design

      A group of 20 people with type 2 diabetes and 10 control subjects are twice invited to the
      laboratory, respectively.

      The type 2 diabetes group consist of 10 individuals being treated with metformin and 10
      individuals who are not being treated with Metformin. The latter group may be diet-treated
      diabetics or diabetics who have stopped taking their oral antidiabetic agent for 72 hours
      before the day of the experiment.

      On the first visit, the following is carried out:

        -  DXA scan, blood pressure measurement, determination of ECG and VO2-max on a
           cycleergometer

        -  Blood sample

        -  Questionnaire about everyday physical activity (I-PAQ)

      On the second visit, the following is carried out:

        -  3 days of carbohydrate loading prior to this day.(By diet recommendations).

        -  Insertion of arterial cannula, blood sample extraction.

        -  Insertion of venus cannula. Insertion of stable glucose isotopes over a period of 4.5
           hours: 2,5 hours of relaxation in bed followed by 45 minutes of cycling on an exercise
           bicycle (during continued isotope infusion) at 60% of maximum heart rate reserve, which
           was measured on test day 1. Followed by relaxation with continued blood sampling and
           isotope infusion, one hour after cycling ceased.

      Inclusion criteria

        -  Age between 30 and 60 years old,

        -  Maximum oxygen consumption between 20 and 50 ml/kg/minute,

        -  BMI between 25 and 35 kg/m2,

        -  Normal ECG,

        -  Must have a stable weight throughout the last three months and have a normal balanced
           diet,

        -  Can cycle for 45 minutes

      Exclusion criteria

        -  For patients with type 2 diabetes: insulin treatment,

        -  ECG that indicates cardiovascular disease,

        -  Illness or medicine that may affect the results,

        -  On-going weight loss diet

      DXA scan

      Minimal radiation - The scan lasts from six to 10 minutes and the total radiation dose with
      measuring is below 0.01 mSv (millisievert). This is approximately equivalent to the natural
      daily background exposure.

      Cycling test

      Prior to this test, an ECG is carried out and the person is quizzed about his/her state of
      health. Regarding all experiments, there is quick access to doctors in the laboratory. The
      laboratory is equipped with a defibrillator.

      Infusion with stable glucose isotopes

      Stable glucose isotopes occur naturally in the body, though in much smaller amounts. They are
      not radioactive and require no special precautions.

      Blood sampling

      An arterial cannula is inserted, from which blood samples are subsequently taken. A sample is
      immediately analysed (ABL analyser) for glucose and lactate concentrations and blood gases,
      Hgb and Hct.

      Other blood samples are processed on a centrifuge and the plasma is frozen at - 80 °C until
      it will be analysed.

      The plasma is analysed to determine concentrations of:

      Insulin, glucagon, cortisol, growth hormone (GH), adrenocorticotrophic hormone
      (ACTH),C-peptide, catecholamines , alanin, concentration of ketone, cholesterol free fatty
      acids,glycerol, glucose isotope (Ra) content before, during and after the cycling.

      The biological material (in the form of plasma) will be stored in a freezer. When the
      experiment is completed, the material will be analysed in our laboratories. When all of the
      analysis has been carried out, any excess materials will be destroyed. All materials will be
      stored anonymously.

      Ethical considerations

      At all times, the study will be carried out in accordance with the latest of Helsinki and
      current Danish legislation.

      Among other things, this includes voluntary participation and that test subjects can withdraw
      their consent at any time and without having to provide any explanation.

      The study protocol and the written patient information will be submitted to the Research
      Ethics Committee of the Capital Region of Denmark and the Danish Data Protection Agency will
      be informed. Patient inclusion cannot begin until a written approval has been received from
      both of these institutions. Both positive and, negative and inconclusive results must be
      published.
    

Intervention name(s): 45 minutes of moderate exercise at the fasted state. Before test day 2: 3 days of carbohydrate loading.
Intervention type(s): Other
Other intervention name(s): exercise performed at 60% of heart rate reserve.
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        -  10 type 2 Diabetics without medication

          -  10 type 2 Diabetics on Metformin treatment

          -  10 matched healthy controls
      
Biospecimen description: 
      whole blood and plasma
    
Keywords: glucose homeostasis; endogenous glucose production; moderate exercise; type 2 diabetes; metformin