Hyperglycemia, Myokine, Normoglycemia
Conditions
Keywords
Myokine, Insulin sensitivity, Exercise, Skeletal muscle
Brief summary
Normal glucose uptake and metabolism in skeletal muscles are essential to keep blood glucose within normal range and hence, insulin resistance (possibly mediated by inflammatory processes) in skeletal muscle is a major pathogenic factor in type 2 diabetes. Physical activity seems to be of essential importance in the prevention and treatment of type 2 diabetes. Myokines are proteins secreted from skeletal muscle that can execute important biological functions locally in the muscle (paracrine) or in other organs like the brain, heart and pancreas (endocrine). Evidence suggest that several interleukines and other cytokines are secreted by skeletal muscles. In the present project, the investigators will explore the relation between secreted myokines from muscle cells, insulin resistance and glucose metabolism before and after 12 weeks of exercise intervention. Subjects with normal as well as impaired glucose metabolism will be included in the study.
Interventions
OTHERExercise
12 weeks of exercise; 4 times pr week
Sponsors
University of Oslo
Norwegian School of Sport Sciences
Oslo University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
40 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male * Age 40-65 years * Nordic ethnicity * Non-smoker 1. Either (participants with impaired glucose metabolism): Body Mass Index (BMI) 27-32 kg/m2 and abnormal glucose metabolism, defined as: i. impaired fasting glucose (FPG ≥ 5.6 mmol/L) ii. impaired glucose tolerance (2 h PG ≥7.8 mmol/L) iii. type 2 diabetes (no medication, HbA1c ≤7.5%) 2. Or (controls): BMI 19-25 kg/m2 and normal glucose metabolism and no first degree relatives with type 2 diabetes.
Exclusion criteria
1. Subjects having type 1 diabetes or medically treated type 2 diabetes. 2. Systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 90 mmHg at screening 3. Significant hematological or renal disease or chronic renal impairment, GFR\< 50 ml/min. 4. Significant liver disease or ALAT \>3x UNL. 5. Chronic inflammatory disease in active phase or long-term use of corticosteroids last 3 months. 6. Use of anti-diabetic agents, lipid lowering drugs, antihypertensive medication, ASA or any other drug not deemed suitable by the study physician. 7. Mental condition (psychiatric or organic cerebral disease), drug or alcohol abuse rendering the subject unable to understand the nature, scope and possible consequences of the study. 8. BMI outside inclusion criteria. 9. Smoker 10. Any medical or other condition that in the judgment of the investigator would jeopardize the subject's safety or evaluation of the intervention for efficacy and safety 11. Exercising regularly (\>1 times pr week)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in gene expression changes in skeletal and adipose tissue | Baseline and after 12 weeks, and before, 0 hr and 2 hours after acute exercise |
| Changes from baseline in plasma/serum levels of selected proteins | Baseline and after 12 weeks, and before, 0 hr and 2 hour |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline in muscle strength | Before and after 12 weeks | — |
| Change from baseline in insulin sensitivity | Before and after 12 weeks of exercise | Insulin sensitivity will be measured using the euglycaemic hyperinsulinaemic clamp technique. |
| Changes from baseline in heart frequency | Before and after 12 weeks | — |
| Changes from baseline in body composition | Before and after 12 weeks | Body composition will be estimated with whole body MRI. |
| Changes in baseline from maximal oxygen uptake VO2 max | Before and after 12 weeks | — |
Outcome results
None listed