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Trial record 28 of 668 for:    Recruiting, Not yet recruiting, Available Studies | "Insulins"

Abnormalities in the Effects of Insulin and Exercise on Glucose- and Lipid Metabolism in Obesity and Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT03500016
Recruitment Status : Recruiting
First Posted : April 17, 2018
Last Update Posted : April 19, 2018
Sponsor:
Collaborator:
Department of Sports Science, University of Southern Denmark
Information provided by (Responsible Party):
Maria Houborg Petersen, Odense University Hospital

Brief Summary:

Type 2 diabetes are characterized by insulin resistance in skeletal muscle. Insulin resistance plays a major role for the increased risk of heart disease seen in type 2 diabetes. No specific treatment of insulin resistance is currently available, except from increased physical activity and weight-loss.

Insulin resistance is characterized by abnormalities in the use of glucose and fat in the muscle, and is associated with abnormal function and content of mitochondria (the power houses of our cells) as well as increased levels of fat within the muscle.

The investigators believe that abnormalities in the use of glucose and fat in muscle cells in response to insulin and exercise can explain why insulin resistance is associated with abnormal function and content of mitochondria and an increased amount of fat in skeletal muscle of patients with type 2 diabetes and individuals with obesity. The major purpose of our project is, therefore, to investigate the effect of insulin in physiological concentrations and the effect of both acute exercise and 8 weeks of exercise-training on

  1. insulin sensitivity and energy metabolism,
  2. insulin signaling,
  3. mitochondrial dynamics and mitophagy,
  4. regulators of storage of fat into lipid droplets and their interaction with mitochondria in skeletal muscle
  5. acetylation and phosphorylation of enzymes (proteins) in major metabolic and signaling pathways, as well as
  6. transcriptional and signalling networks regulating mitochondrial biogenesis and substrate metabolism.

The effects of insulin in physiological concentrations and novel exercise-interventions combining biking and rowing will be studied in a comprehensive study of obese patients with type 2 diabetes compared with weight-matched obese and lean healthy controls.

The effects of insulin and exercise on whole-body metabolism will be evaluated by measurement of maximal oxygen consumption, and well-known methods to determine insulin-stimulated glucose utilization and use of glucose and fat. Skeletal muscle and fat tissue samples obtained under these conditions will be used for assessment of tissue-levels of specific sets of genes and enzymes known to be involved in insulin action, quality and size of mitochondria, and storage of fat into lipid droplets and their interaction with mitochondria. This project is expected to provide important and novel insight into the causal relationship between insulin resistance, accumulation of fat and abnormal content and function of mitochondria in skeletal muscle in type 2 diabetes.

The investigators ultimately expect that our findings will help us to identify novel molecules or enzymatic pathways, which can be used to develop drugs that can enhance or mimic the effects of insulin and exercise, and hence be used in the prevention and treatment of type 2 diabetes and heart disease.


Condition or disease Intervention/treatment Phase
Type2 Diabetes Insulin Resistance Other: Acute exercise Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Metabolic and Molecular Abnormalities in Response to Insulin and Exercise in Obesity and Type 2 Diabetes
Actual Study Start Date : February 26, 2018
Estimated Primary Completion Date : November 12, 2020
Estimated Study Completion Date : November 12, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Insulin

Arm Intervention/treatment
Experimental: Acute exercise and exercise training
Euglycemic-hyperinsulinemic clamp before and after 8 weeks supervised exercise training. Before exercise training the participants will also do an "acute exercise" on 1 hour with muscle biopsies taken before and after exercise and then again 4 hours into recovery.
Other: Acute exercise
See under arm description.
Other Name: Exercise training




Primary Outcome Measures :
  1. Insulin sensitivity [ Time Frame: 26.02.2018-12.11.2020 ]
    Determined by euglycemic-hyperinsulinemic clamp before and after 8-weeks exercise training

  2. Mitichondrial respiration [ Time Frame: 26.02.2018-12.11.2010 ]
    Measurements of mitochondrial respiration in permeabilized muscle fiber using a high-resolution respirometer

  3. Gene expression changes in muscle and fat biopsies [ Time Frame: 26.02.2018-12.11.2020 ]
    TaqMan gene expression assays for all relevant genes

  4. Protein abundance and phosphorylation of all enzymes of interest [ Time Frame: 26.02.2018-12.11.2020 ]
    Protein abundance and phosphorylation of all enzymes of interest will be studied in human skeletal muscle and fat biopsies by Western blotting and quantified by densitometry in arbitrary units.

  5. Lipid droplet function, morphology, and interaction with mitochondria [ Time Frame: 26.02.2018-12.11.2020 ]
    Studies of genes and enzymes involved in the regulation of lipid droplets and their morphology and interaction with mitochondria in muscle biopsies determined by gene expression, Westen blotting and transmission electron microscopy (immunogold-labelling), all measured in arbitrary units

  6. mRNA levels and protein content and/or phosphorylation of regulators of adipose tissue expandability, mitochondrial dynamics and mitophagy, LD function, and transcriptional and signaling networks regulated by exercise [ Time Frame: 26.02.2018-12.11.2020 ]
    Determined by quantitative real-time PCR and Western blotting


Secondary Outcome Measures :
  1. Maximal oxygen consumption [ Time Frame: 26.02.2018-12.11.2020 ]
    Determined before and after 8-weeks exercise training by a graded maximal test on a cycle ergometer using indirect calorimetry.

  2. Whole body composition (lean body mass, total, and regional fat mass) [ Time Frame: 26.02.2018-12.11.2020 ]
    Determined before and after 8-weeks exercise training by a DXA-scan.


Other Outcome Measures:
  1. HbA1c [ Time Frame: 26.02.2018-12.11.2020 ]
    Determined by blood tests before and after 8-weeks exercise training

  2. Lipid profile [ Time Frame: 26.02.2018-12.11.2020 ]
    Determined by blood tests before and after 8-weeks exercise training



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:  

Due to biological gender differences, our study does not make it possible to make direct comparisons of data between men and women.

If we had chosen female project participants rather than male, we would also have to take into account whether they were pre- or postmenopausal as well as in the former case where they were in the menstrual cycle during the clamp studies.

Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • GAD65 antibody negative patients with T2D
  • Duration of diabetes 6 months to 10 years
  • No diabetic complications
  • Treated with either diet alone or diet in combination with either metformin, oral DPP-4 inhibitors or sulphonylureas
  • Patients should be able and willing to discontinue all drugs for 1 weeks prior to the studies
  • Obese and lean controls should be healthy, glucose tolerant and drug naive
  • Obese and lean controls should have no family history of diabetes
  • All participants should be able to provide informed written consent

Exclusion Criteria:

  • Any unknown disease or need for medication that occurs after inclusion
  • Abnormal ECG, screening blood tests and/or severe hypertension
  • Impaired glucose tolerance in non-diabetic subjects

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03500016


Contacts
Contact: Maria H Petersen, MD +0045 51427331 maria.petersen@rsyd.dk
Contact: Kurt Højlund, Professor, DMSc, PhD, MD kurt.hoejlund@rsyd.dk

Locations
Denmark
Department of Endocrinology, Odense University Hospital Recruiting
Odense, Denmark, 5000
Contact: Maria H Petersen, MD    +0045 51427331    maria.petersen@rsyd.dk   
Contact: Kurt Højlund, Professor, DMSc, PhD, MD       kurt.hoejlund@rsyd.dk   
Principal Investigator: Kurt Højlund, Professor, DMSc, PhD, MF         
Principal Investigator: Maria H Petersen, MD         
Sponsors and Collaborators
Odense University Hospital
Department of Sports Science, University of Southern Denmark
Investigators
Principal Investigator: Kurt Højlund, Professor, DMSc, PhD, MD Department of Endocrinology, Odense University Hospital

Responsible Party: Maria Houborg Petersen, MD, PhD student, Odense University Hospital
ClinicalTrials.gov Identifier: NCT03500016     History of Changes
Other Study ID Numbers: 17/31977
First Posted: April 17, 2018    Key Record Dates
Last Update Posted: April 19, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Maria Houborg Petersen, Odense University Hospital:
Insulin resistance
Obesity
Type 2 diabetes
Exercise training

Additional relevant MeSH terms:
Insulin Resistance
Diabetes Mellitus
Obesity
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperinsulinism
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs