Cellular Adaptations to Training in Patients With Type 2 Diabetes
NCT ID: NCT04945551
Last Updated: 2021-06-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
NA
30 participants
INTERVENTIONAL
2021-02-20
2023-10-31
Brief Summary
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The aim of this project is to study the transcriptional differences in skeletal muscle and adipose tissue at baseline and after a 3-month physical training program in obese patients with and without T2D and to use this information to identify novel therapeutic targets for improvement of glucose disposal and insulin sensitivity in patients with T2D.
Thus, the investigators aim to find answers to the question: What is the mechanism behind the effect of physical activity on insulin sensitivity in type 2 diabetes?
Detailed Description
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Physical training can improve metabolic health in patients with insulin resistance and/or type 2 diabetes (T2D). The cellular and molecular changes underlying the improvements in metabolic health are multi-factorial and only partly understood, but most likely involve adaptation at a multi-organ level that includes improvements in skeletal muscle glucose uptake and adipose tissue insulin sensitivity.
The literature on the effects of an acute bout of exercise on glucose uptake in skeletal muscle is large, but so far, there is a lack of studies investigating the specific molecular basis for the insulin sensitizing effect of regular physical training.
The aim of this project is to study the transcriptional differences in skeletal muscle and adipose tissue at baseline and after a 3-month physical training program in obese patients with and without T2D and to use this information to identify novel therapeutic targets for improvement of glucose disposal and insulin sensitivity in patients with T2D.
Thus, the investigators aim to find answers to the question: What is the mechanism behind the effect of physical activity on insulin sensitivity in type 2 diabetes?
Methods
Thirty obese patients with (n=15) and without (n=15) type 2 diabetes will be included in the study.
Design: Cohort Study Intervention: 12 weeks intervention period consisting of aerobic exercise training 3 sessions/week, 45 min/session. All training sessions are supervised. Aerobic training is conducted as ergometer bicycle training at an intensity of 70% of maximal oxygen uptake (x2/wk.) and rowing ergometer exercise at 70% of maximal heart rate (x1/wk.). In week 3, 6 and 9 VO2max is measured to ensure sufficient adjustment of the workload during the training sessions.
Experimental methods: Before (1-2 weeks) and after the intervention, the following tests and measurements are performed:
Day A: (Overnight fasting. Duration approx. 3 h)
* Dual energy x-ray absorptiometry (DXA) scan (body composition and body fat)
* Graded exercise test on an ergometer bike (maximal fat oxidation rate)
* Maximal oxygen consumption test (VO2max)
* Handgrip strength (by dynamometer)
* Leg power (Power Rig and sit-to-stand test)
Day B: (Overnight fasting. Duration approx. 9 h)
* 2-step euglycemic, hyperinsulinemic clamp
* Muscle biopsy vastus lateralis
* Fat biopsy subcutaneous lower abdomen
* Flow measurements (Femoral artery by Doppler ultrasound and forearm by strain-gauge plethysmography)
* Energy expenditure (ventilated hood method)
Day A and B are repeated after the training intervention has finished.
Analytical methods:
1. Muscle and fat biopsies: Mitochondrial respiratory capacity and reactive oxygen species production. Single nuclei RNA sequencing (snSeq). Fiber type determination and capillarization.
2. Blood samples: Hormones, metabolites and substrates (e.g. insulin, catecholamines, cortisol, glucose, lactate, pyruvate, ketone bodies, cytokines, and myokines). Plasma proteomic/peptidomic analysis.
In summary, this study will reveal cell types and genes in skeletal muscle and adipose tissue that are affected by training and/or that shows differential regulation in patients with T2D versus control subjects.
Statistical considerations:
A power calculation indicates that a significant difference in training induced insulin sensitivity will be detectable when n ≥ 10, based on power = 0.95 and level of significance set to P\<0.05. This allows for a dropout rate of a 15-20% with some margin. Mixed model analysis will be used for data analysis of phenotypical data, and bioinformatical tools for the snSeq data and for the interaction between gene- and phenotype expression.
Ethical considerations:
The project was approved by The Regional Ethical Committee of the Capital Region (H-20046605) the 15th of December 2020.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
BASIC_SCIENCE
NONE
Study Groups
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Diabetes
Aerobic exercise training
Aerobic exercise training
12 weeks intervention period consisting of aerobic exercise training 3 sessions/week, 45 min/session. All training sessions are supervised. Aerobic training is conducted as ergometer bicycle training at an intensity of 70% of maximal oxygen uptake (x2/wk.) and rowing ergometer exercise at 70% of maximal heart rate (x1/wk.). In week 3, 6 and 9 VO2 max is measured to ensure sufficient adjustment of the workload during the training sessions.
Healthy
Aerobic exercise training
Aerobic exercise training
12 weeks intervention period consisting of aerobic exercise training 3 sessions/week, 45 min/session. All training sessions are supervised. Aerobic training is conducted as ergometer bicycle training at an intensity of 70% of maximal oxygen uptake (x2/wk.) and rowing ergometer exercise at 70% of maximal heart rate (x1/wk.). In week 3, 6 and 9 VO2 max is measured to ensure sufficient adjustment of the workload during the training sessions.
Interventions
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Aerobic exercise training
12 weeks intervention period consisting of aerobic exercise training 3 sessions/week, 45 min/session. All training sessions are supervised. Aerobic training is conducted as ergometer bicycle training at an intensity of 70% of maximal oxygen uptake (x2/wk.) and rowing ergometer exercise at 70% of maximal heart rate (x1/wk.). In week 3, 6 and 9 VO2 max is measured to ensure sufficient adjustment of the workload during the training sessions.
Eligibility Criteria
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Inclusion Criteria
* Normal resting ECG
Specific for patients with T2D:
* In antiglycemic treatment with diet +/- metformin, SLGT-2 inhibitors, sulfonylurea, GLP1-RA, or DPPV-4 inhibitors
* Time since diagnosis max 4 yrs
Exclusion Criteria
* Epilepsy
* Kidney disease (GFR\<50 ml/min)
* Regular exercise activity
* Inability to perform bicycling and rowing ergometer exercise
* Inability to understand Danish language (written and spoken)
Specific for patients with T2D:
\- Insulin treatment
40 Years
60 Years
ALL
Yes
Sponsors
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Novo Nordisk A/S
INDUSTRY
University of Copenhagen
OTHER
Responsible Party
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Flemming Dela
Professor
Principal Investigators
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Flemming Dela, MD, DMSc
Role: PRINCIPAL_INVESTIGATOR
University of Copenhagen
Locations
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Xlab, Faculty of Health and Medical Sciences, University of Copenhagen
Copenhagen, , Denmark
Countries
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Central Contacts
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Facility Contacts
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Flemming Dela, MD, DMSc
Role: primary
Other Identifiers
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Training Adaptations in T2D
Identifier Type: -
Identifier Source: org_study_id