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.

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.

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

• 10 type 2 Diabetics without medication
• 10 type 2 Diabetics on Metformin treatment
• 10 matched healthy controls