Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose of this study is to evaluate the potential interaction between metformin and exercise in order to optimize clinical guidelines for treatment of T2D.
Detailed description
Physical activity is a first line treatment for patients with type 2 diabetes (T2D ), however, the vast majority of patients with T2D do not achieve satisfying glycemic control with physical activity alone, which is why pharmacological treatment with metformin is most often initiated. It is known that metformin and exercise both activates AMPK, which results in many different metabolic effects. Because of this similarity, an interaction between metformin and exercise is plausible, but knowledge in the area is sparse. With this study the investigators aim to look at the individual and combined effects of metformin and exercise in order to investigate whether an interaction occur. An Interaction will have tremendous clinical importance for patients with T2D given current guidelines where the vast majority of these patients are recommended both exercise and metformin treatment. The investigators hypothesize that metformin treatment reduces self-selected exercise intensity, which may be explained via decreased mitochondrial complex 1 function, increased blood lactate levels, heart rate and RPE during exercise. Furthermore exercise-induced AMPK-activation is reduced with metformin treatment.
Interventions
DRUGMetformin
17 days treatment with metformin
OTHERPlacebo
17 days treatment with placebo
Sponsors
University of Copenhagen
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* male * HbA1c \< 39 mmol/l * BMI \< 25 * structured physical activity \< = 150 min/week * apparently healthy
Exclusion criteria
* smoking * daily pharmaceutical treatment * contraindication to increased levels of physical activity * ALAT/ASAT elevated 3 times above upper normal values * renal insufficiency (eGFR \< 60 ml/min) * prior history of lactic acidosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall aerobic work performed during an exercise bout with self-selected intensity | Total oxygen consumption (L O2) during a 45 min ergometer cycling bout with self-selected intensity |
Secondary
| Measure | Time frame |
|---|---|
| External work performed during an exercise bout with self-selected intensity | Total work produced (kJ) during a 45 min ergometer cycling bout with self-selected intensity |
| Rate of perceived exertion during an exercise bout with fixed intensity | Mean rate of perceived exertion (Borg scale) during a 45 min ergometer cycling bout with fixed intensity |
| blood lactate during an exercise bout with fixed intensity | Mean blood lactate (mmol/l) during a 45 min ergometer cycling bout with fixed intensity |
| Respiratory exchange ratio during an exercise bout with fixed intensity | Mean VCO2/VO2 during a 45 min ergometer cycling bout with fixed intensity |
| Physical fitness (VO2max) | maximal oxygen consumption (L/min) during a VO2 max test |
| Heartrate during an exercise bout with fixed intensity | Mean heart rate (bpm) during a 45 min ergometer cycling bout with fixed intensity |
Other
| Measure | Time frame |
|---|---|
| AMPK-activation in skeletal muscle during an exercise bout with fixed intensity | change in exercise induced AMPK-activation after compared to before a 45 min ergometer cycling bout with self-selected intensity |
| Oxidative phosphorylation in skeletal muscle fibers | Mitochondrial Complex I respiration in skeletal muscle tissue after 17 days of metformin/placebo treatment |
Countries
Denmark
Outcome results
None listed