Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity

NCT ID: NCT03065140

Last Updated: 2022-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2019-01-31

Brief Summary

Early research found that high levels of fat within muscle meant poorer control of blood sugar. However, more recent research has shown that athletes have similar levels of fat within muscle, but in contrast, they have very good control of blood sugar. The investigators are not sure why this is and want to find out if the fat within muscle can be changed to improve blood sugar control, as good blood sugar control reduces the risk of heart disease, diabetes and stroke.

Detailed Description

Higher levels of triglycerides (TG) and diacylglycerols (DAG) are found in skeletal muscle of patients with obesity/diabetes as well as in trained athletes. Despite similar metabolic storage, patients and athletes have opposite insulin sensitivity phenotypes and an explanation for this is lacking. The investigators' objective is to understand how these fat compartments can be beneficially modulated to improve insulin resistance and cardio-metabolic risk. The investigators will investigate if either structural differences (saturated versus unsaturated balance of TG and DAG side-chains) or different handling abilities (fast versus slow lipid pool turnover) will be induced by exercise capacity interventions in athletes and in diabetic patients. In a longitudinal study pre- and post-exercise, the investigators will use novel, non-invasive 1H-Magnetic Resonance Spectroscopy to benchmark the saturated/unsaturated compartments against skeletal muscle biopsies for the first time and stable isotope analysis for fat compartments' rate of turnover.

Conditions

Diabetes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy Volunteers

Healthy volunteers will undergo the following:

• CPEX with/without stable isotope infusion
• Muscle biopsies
• Magnetic Resonance Spectroscopy Followed by a period of detraining.

They will then undergo the following:

• CPEX with/without stable isotope infusion
• Muscle biopsies
• Magnetic Resonance Spectroscopy

Group Type: EXPERIMENTAL

Training or detraining

Intervention Type: OTHER

A period of detraining or a supervised exercise program.

Diabetic Patients

Diabetic patients will undergo the following:

• CPEX with/without stable isotope infusion
• Muscle biopsies
• Magnetic Resonance Spectroscopy They will then undergo a supervised training period.

They will then undergo the following:

• CPEX with/without stable isotope infusion
• Muscle biopsies
• Magnetic Resonance Spectroscopy

Group Type: EXPERIMENTAL

Training or detraining

Intervention Type: OTHER

A period of detraining or a supervised exercise program.

Interventions

Training or detraining

A period of detraining or a supervised exercise program.

Intervention Type: OTHER

Other Intervention Names

Detraining or training

Eligibility Criteria

Inclusion Criteria

• Type 2 diabetic patients, aged between 20-65, diagnosed as per WHO criteria, diet controlled or diet and any of the following oral hypoglycemics: metformin, sulphonylureas, glitazones, gliptins, acarbose, but not requiring insulin for controlling of blood glucose.
• Trained, athletic healthy controls, aged 18 and over.
• Participant who is willing and able to give informed consent for participation in the study.
• Able to perform exercise testing.

Exclusion Criteria

• Any history of known coronary artery disease.
• Other endocrine conditions
• Impaired renal function defined as eGFR<60mls/min/1.73m2
• Known resting/24 hour BP >160/100mmHg
• Participants on ACE inhibitors
• Participants on PPAR agonists
• Participants on omega 3 fatty acids
• The existence of any medical or surgical condition that in the judgement of the investigators may interfere with the exercise regime, FA metabolism or may compromise the safety of the subject
• Presence of other significant concomitant heart diseases such as ischaemic, valvular, pericardial heart disease or cardiomyopathy, skeletal muscle disorders
• Healthy volunteers that are on any chronic medication that in the judgment of the investigators is likely to affect the outcome of the study
• Significant asthma
• Significant pulmonary disease
• Participants unable to cycle on the ergometer
• Unable to perform exercise testing (e.g. prosthetic limbs)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

NHS Grampian

OTHER_GOV

Sponsor Role: collaborator

University of Aberdeen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dana Dawson, MD

Role: PRINCIPAL_INVESTIGATOR

University of Aberdeen Employee

Locations

Cardiac Research Office

Aberdeen, Aberdeenshire, United Kingdom

Countries

United Kingdom

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Other Identifiers

16/NS/0024

Identifier Type: -

Identifier Source: org_study_id