NCT03500016

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 high intensity interval exercise-training on

  1. 1.insulin sensitivity, body composition, cardiorespiratory fitness and energy metabolism,
  2. 2.insulin signaling, mitochondrial dynamics and mitophagy in skeletal muscle

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Feb 2018

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 2, 2018

Completed
24 days until next milestone

Study Start

First participant enrolled

February 26, 2018

Completed
2 months until next milestone

First Posted

Study publicly available on registry

April 17, 2018

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 12, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 12, 2021

Completed
Last Updated

September 2, 2022

Status Verified

August 1, 2022

Enrollment Period

3.7 years

First QC Date

February 2, 2018

Last Update Submit

August 31, 2022

Conditions

Type2 DiabetesInsulin Resistance

Keywords

Insulin resistanceObesityType 2 diabetesExercise training

Outcome Measures

Primary Outcomes (3)

  • Insulin sensitivity

    Determined by euglycemic-hyperinsulinemic clamp, DXA-scans and VO2max test before and after 8-weeks HIIT

    26.02.2018-12.11.2020

  • Whole body composition (lean body mass, total, and regional fat mass)

    Determined before and after 8-weeks HIIT by a DXA-scan.

    26.02.2018-12.11.2010

  • Cardiorespiratory fittness/maximal oxygen consumption

    Determined before and after 8-weeks HIIT by a graded maximal test on a cycle ergometer using indirect calorimetry.

    26.02.2018-12.11.2020

Secondary Outcomes (5)

  • Insulin secretion adjusted for insulin sensitivity

    26.02.2018-12.11.2020

  • Lipid droplet function, morphology, and interaction with mitochondria

    26.02.2018-12.11.2020

  • Global gene expression and protein changes in muscle and fat biopsies and mRNA levels of selected genes in fat or muscle

    26.02.2018-12.11.2020

  • Protein abundance and phosphorylation of all enzymes of interest

    26.02.2018-12.11.2020

  • Plasma and tisue metabolomics

    26.02.2018-12.11.202

Other Outcomes (2)

  • HbA1c, insulin, glucose, selected adipokines, myokines, hepatokines (exerkines)

    26.02.2018-12.11.2020

  • Lipid profile

    26.02.2018-12.11.2020

Study Arms (1)

Acute exercise and high intensity interval training

EXPERIMENTAL

Euglycemic-hyperinsulinemic clamp, IVGTT, DXA scan, VO2max, plasma samples, fat and muscle biopsies before and after 8 weeks supervised high intensity interval training (HIIT). Before the 8 weeks HIIT-protocol the participants will also perform an 1-h acute exercise with plasma samples and musce samples before and immediately after the exercise bout and 4 hours into recovery

Other: High intensity interval training

Interventions

High intensity interval trainingOTHER

See under arm description.

Also known as: Acute exercise
Acute exercise and high intensity interval training

Eligibility Criteria

Age40 Years - 65 Years
Sexmale(Gender-based eligibility)
Gender Eligibility DetailsDue 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.
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Abnormal ECG, screening blood tests and/or severe hypertension
  • Impaired glucose tolerance in non-diabetic subjects

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Endocrinology, Odense University Hospital

Odense, 5000, Denmark

Location

Related Publications (1)

  • Houborg Petersen M, Stidsen JV, Eisemann de Almeida M, Kleis Wentorf E, Jensen K, Ortenblad N, Hojlund K. High-intensity interval training combining rowing and cycling improves but does not restore beta-cell function in type 2 diabetes. Endocr Connect. 2024 Apr 12;13(5):e230558. doi: 10.1530/EC-23-0558. Print 2024 May 1.

    PMID: 38513367DERIVED

MeSH Terms

Conditions

Insulin ResistanceObesityDiabetes Mellitus, Type 2

Interventions

High-Intensity Interval TrainingExercise

Condition Hierarchy (Ancestors)

HyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesOverweightOvernutritionNutrition DisordersBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsDiabetes MellitusEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Physical Conditioning, HumanMotor ActivityMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological Phenomena

Study Officials

  • Kurt Højlund, Professor, DMSc, PhD, MD

    Department of Endocrinology, Odense University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD student

Study Record Dates

First Submitted

February 2, 2018

First Posted

April 17, 2018

Study Start

February 26, 2018

Primary Completion

November 12, 2021

Study Completion

November 12, 2021

Last Updated

September 2, 2022

Record last verified: 2022-08

Locations

DK(1)