Cellular Adaptations to Training in Patients With Type 2 Diabetes

NCT04945551 | Unknown

• 1 other identifier: Training Adaptations in T2D
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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 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?

Conditions

Diabetes Mellitus, Type 2

Keywords

Diabetes Mellitus, Type 2; Aerobic exercise; Insulin sensitivity

Outcome Measures

Primary Outcomes (3)

• Insulin sensitivity

  Euglycemic hyperinsulinemic clamp

  Change from baseline at 12 weeks

• Blood flow

  Pulsed-wave Doppler ultrasound (A. femoralis) and venous occlusion strain-gauge plethysmography (forearm)

  Change from baseline at 12 weeks

• Gene expression will be quantitatively determined at cellular resolution using single nuclei sequencing

  The snSeq data will be analysed using state of the art computational approaches to detect changes in cell type composition and differences in gene expression patterns of specific cell types. These approaches will include: I) normalizations of raw counts; II) feature selection based on most variable genes; III) Conos or Canonical correlation analysis to align the cells across samples; IV) Visualization using dimensionality reduction approaches such as Uniform Approximation and Projection (UMAP) and t-distributed Stochastic Neighbour Embedding (t-SNE); V) RNA velocity and trajectory inference methods to follow changes in cell type identities.

  Change from baseline at 12 weeks

Secondary Outcomes (2)

• Glucose homeostasis

  Change from baseline at 12 weeks

• Cardiorespiratory fitness

  Baseline and after 3, 6, 9 and 12 weeks of aerobic exercise training

Study Arms (2)

Diabetes

EXPERIMENTAL

Aerobic exercise training

Behavioral: Aerobic exercise training

Healthy

EXPERIMENTAL

Aerobic exercise training

Behavioral: Aerobic exercise training

Interventions

Aerobic exercise training BEHAVIORAL

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.

Diabetes; Healthy

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Overweight to obese (BMI 28-35 kg/m2)
• 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

You may not qualify if:

• Diagnosed with cardiovascular disease (minor to moderate hypertension allowed, defined as prescribed maximally two different antihypertensive drugs)
• 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

Sponsors & Collaborators

• University of Copenhagen: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Xlab, Faculty of Health and Medical Sciences, University of Copenhagen

Copenhagen, 2200, Denmark

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Study Officials

• Flemming Dela, MD, DMSc

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Hansen, MD

CONTACT

+4529210442; mariahan@sund.ku.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Thirty obese patients with (n=15) and without (n=15) type 2 diabetes will be included in the study. Both groups will undergo a 12-week aerobic exercise training intervention.

Study Record Dates

• First Submitted: June 7, 2021
• First Posted: June 30, 2021
• Study Start: February 20, 2021
• Primary Completion: July 1, 2022
• Study Completion: October 1, 2023
• Last Updated: June 30, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)