Effect of Metformin on Exercise-induced Lipolysis

Study Overview
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Brief Summary
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The aim of this study is to investigate whether metformin has inhibitory effect on exercise-induced lipolysis in subcutaneous adipose tissue in healthy lean man. Ten healthy lean mean will follow protocols consisting of 60 minutes of exercise on bicycle ergometer combined with a) orally administered metformin and b) locally administered metformin into adipose tissue and c) without metformin treatment. Microdialysis is used for assessment of metabolites in situ in subcutaneous adipose tissue.

Detailed Description
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Metformin and physical activity are often recommended as the first therapeutic agents to improve glycemic control for prediabetes and type 2 diabetes (ADA). It has been reported that metformin decrease plasma concentration of non-esterified fatty acids in patients with type 2 diabetes which might be associated with the inhibition of lipolysis in adipose tissue. However, the inhibition of lipolysis during physical exercise, would not be probably beneficial. Thus, the effect of metformin on lipolysis during exercise is investigated in this protocol. As the lipolysis regulation is often impaired in obese and diabetic patients, the healthy lean men were chosen for this pilot study. Glycerol will be analyzed as a measure of lipolytic rate in adipose tissue and in plasma. Lactate levels will be observed. Our findings should provide a new background about the combination of physical activity and metformin medication.

Official Title
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New Electrophoretic Approaches in Studies of Obesity and Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Metformin Oral
* Drug: Metformin local in AT
* Other: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy lean men, non obese, BMI 20-28 kg/m2 Exclusion Criteria: weight change within the 3 months before the study, hypertension, impaired fasting glucose diabetes hyperlipidemia drug or alcohol abuse smoking

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin oral +exercise<br>Metformin, one dose 2000mg, 2.5h before the start of 60 min physical exercise | Drug: Metformin Oral<br> <br> * Other names: Metformin tablet;Other: Exercise<br> <br> * Other names: Acute exercise;|
| Active Comparator: Metformin local in AT +exercise<br>Metformin perfused into microdialysis probe inserted in adipose tissue, 0.3ug/min 1.5h before the exercise and during 60min physical exercise | Drug: Metformin local in AT<br> <br> * Other names: Metformin dialysate;Other: Exercise<br> <br> * Other names: Acute exercise;|
| Active Comparator: No metformin + exercise<br>60min physical exercise without pretreatment of metformin | Other: Exercise<br> <br> * Other names: Acute exercise;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in adipose tissue lipolysis in response to exercise | Glycerol concentration in dialysate outcoming from adipose tissue and in plasma - kinetic study | Minute -60, 15, 30, 45, 60 and 120 from the start of exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lactate production in response to exercise | Concentration of lactate in dialysate and in plasma - kinetic study | Minute -60, 15, 30, 45, 60 and 120 from the start of exercise | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lipolysis, adipose tissue, exercise