DiabetesMISTYNCT03065140

Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity

A study testing Training or detraining in people with Diabetes, run by University of Aberdeen at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years, men onlyHealthy volunteers can take part
Conditions the study is for: Diabetes
What is being tested?: Training or detraining
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: 1 siteUnited Kingdom
Study dates: Sep 2016to Jan 2019
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
Men only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 14Show fewer

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)

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Cardiac Research Office
Aberdeen, Aberdeenshire, AB25 2ZN

Other trials in United Kingdom

About this study

Official title: Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity - the MISTY Study

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.

Read the 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
Being tested: Training or detraining
Medical subject headings: Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Training or detrainingOther
Also called Detraining or training
A period of detraining or a supervised exercise program.

Study groups in NCT03065140
Study group	Role	What they receive
Healthy Volunteers	Experimental	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 Receives: Other: Training or detraining
Diabetic Patients	Experimental	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 Receives: Other: Training or detraining

What is being measured

The primary outcome is the main question the study is designed to answer.

Non-invasive 1H Magnetic Resonance Spectroscopy of vastus lateralis
Assessment of energetics of vastus lateralis by MRS
Measured: One Hour

Secondary outcomes (1)

Saturated and unsaturated lipid pool turnover examined by stable isotopes
Lipid pool turnover as examined by stable isotope infusion
Measured: One hour

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2016Jan 2019

First posted27 Feb 2017
Study startSep 2016
Primary completionJan 2019
Study completionJan 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (35)Papers the sponsor has linked to this study.
Other trials for DiabetesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03065140
Sponsor's protocol ID: 16/NS/0024
Acronym: MISTY
Status last verified: Aug 2022
First submitted: 7 Dec 2016
Last updated: 31 Aug 2022
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Lobley GE, Holtrop G, Bremner DM, Calder AG, Milne E, Johnstone AM. Impact of short term consumption of diets high in either non-starch polysaccharides or resistant starch in comparison with moderate weight loss on indices of insulin sensitivity in subjects with metabolic syndrome. Nutrients. 2013 Jun 10;5(6):2144-72. doi: 10.3390/nu5062144.
PubMed 23752495
Wilson FA, van den Borne JJ, Calder AG, O'Kennedy N, Holtrop G, Rees WD, Lobley GE. Tissue methionine cycle activity and homocysteine metabolism in female rats: impact of dietary methionine and folate plus choline. Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E702-13. doi: 10.1152/ajpendo.90670.2008. Epub 2009 Jan 13.
PubMed 19141688
Phillips DI, Caddy S, Ilic V, Fielding BA, Frayn KN, Borthwick AC, Taylor R. Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects. Metabolism. 1996 Aug;45(8):947-50. doi: 10.1016/s0026-0495(96)90260-7.
PubMed 8769349
Kumashiro N, Erion DM, Zhang D, Kahn M, Beddow SA, Chu X, Still CD, Gerhard GS, Han X, Dziura J, Petersen KF, Samuel VT, Shulman GI. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16381-5. doi: 10.1073/pnas.1113359108. Epub 2011 Sep 19.
PubMed 21930939
Goodpaster BH, He J, Watkins S, Kelley DE. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab. 2001 Dec;86(12):5755-61. doi: 10.1210/jcem.86.12.8075.
PubMed 11739435
Amati F, Dube JJ, Alvarez-Carnero E, Edreira MM, Chomentowski P, Coen PM, Switzer GE, Bickel PE, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Diabetes. 2011 Oct;60(10):2588-97. doi: 10.2337/db10-1221. Epub 2011 Aug 26.
PubMed 21873552
Manco M, Mingrone G, Greco AV, Capristo E, Gniuli D, De Gaetano A, Gasbarrini G. Insulin resistance directly correlates with increased saturated fatty acids in skeletal muscle triglycerides. Metabolism. 2000 Feb;49(2):220-4. doi: 10.1016/s0026-0495(00)91377-5.
PubMed 10690948
Anastasiou CA, Kavouras SA, Lentzas Y, Gova A, Sidossis LS, Melidonis A. Diabetes mellitus is associated with increased intramyocellular triglyceride, but not diglyceride, content in obese humans. Metabolism. 2009 Nov;58(11):1636-42. doi: 10.1016/j.metabol.2009.05.019. Epub 2009 Jul 16.
PubMed 19615699
Coen PM, Dube JJ, Amati F, Stefanovic-Racic M, Ferrell RE, Toledo FG, Goodpaster BH. Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Diabetes. 2010 Jan;59(1):80-8. doi: 10.2337/db09-0988. Epub 2009 Oct 15.
PubMed 19833891
Bergman BC, Perreault L, Hunerdosse DM, Koehler MC, Samek AM, Eckel RH. Increased intramuscular lipid synthesis and low saturation relate to insulin sensitivity in endurance-trained athletes. J Appl Physiol (1985). 2010 May;108(5):1134-41. doi: 10.1152/japplphysiol.00684.2009. Epub 2010 Mar 18.
PubMed 20299618
King DS, Dalsky GP, Clutter WE, Young DA, Staten MA, Cryer PE, Holloszy JO. Effects of exercise and lack of exercise on insulin sensitivity and responsiveness. J Appl Physiol (1985). 1988 May;64(5):1942-6. doi: 10.1152/jappl.1988.64.5.1942.
PubMed 3292505
Dube JJ, Amati F, Toledo FG, Stefanovic-Racic M, Rossi A, Coen P, Goodpaster BH. Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide. Diabetologia. 2011 May;54(5):1147-56. doi: 10.1007/s00125-011-2065-0. Epub 2011 Feb 17.
PubMed 21327867
Dube JJ, Amati F, Stefanovic-Racic M, Toledo FG, Sauers SE, Goodpaster BH. Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited. Am J Physiol Endocrinol Metab. 2008 May;294(5):E882-8. doi: 10.1152/ajpendo.00769.2007. Epub 2008 Mar 4.
PubMed 18319352
Goodpaster BH, Katsiaras A, Kelley DE. Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity. Diabetes. 2003 Sep;52(9):2191-7. doi: 10.2337/diabetes.52.9.2191.
PubMed 12941756
Summers SA, Nelson DH. A role for sphingolipids in producing the common features of type 2 diabetes, metabolic syndrome X, and Cushing's syndrome. Diabetes. 2005 Mar;54(3):591-602. doi: 10.2337/diabetes.54.3.591.
PubMed 15734832

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 31 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity - the MISTY Study
ClinicalTrials.gov ID: NCT03065140
Acronym / sponsor ID: MISTY / 16/NS/0024
Conditions: Diabetes
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: University of AberdeenUniversity, hospital or other
Collaborators: NHS Grampian
Study start: Sep 2016 (actual)
Primary completion: Jan 2019 (actual)
Study completion: Jan 2019 (actual)
First posted: 27 Feb 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Healthy Volunteers	Experimental	Other: Training or detrainingHealthy 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
Diabetic Patients	Experimental	Other: Training or detrainingDiabetic 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

Who may qualify

Ages: 18 to 65 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (14 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Training or detrainingAlso: Detraining or trainingA period of detraining or a supervised exercise program.	Other	Diabetic Patients, Healthy Volunteers

Primary outcome

Non-invasive 1H Magnetic Resonance Spectroscopy of vastus lateralis
Time frame: One Hour
Assessment of energetics of vastus lateralis by MRS

1 secondary outcome

Saturated and unsaturated lipid pool turnover examined by stable isotopes
Time frame: One hour

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2022.
Background: PubMed 23752495Lobley GE, Holtrop G, Bremner DM, Calder AG, Milne E, Johnstone AM. Impact of short term consumption of diets high in either non-starch polysaccharides or resistant starch in comparison with moderate weight loss on indices of insulin sensitivity in subjects with metabolic syndrome. Nutrients. 2013 Jun 10;5(6):2144-72. doi: 10.3390/nu5062144.
Background: PubMed 19141688Wilson FA, van den Borne JJ, Calder AG, O'Kennedy N, Holtrop G, Rees WD, Lobley GE. Tissue methionine cycle activity and homocysteine metabolism in female rats: impact of dietary methionine and folate plus choline. Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E702-13. doi: 10.1152/ajpendo.90670.2008. Epub 2009 Jan 13.
Background: PubMed 8769349Phillips DI, Caddy S, Ilic V, Fielding BA, Frayn KN, Borthwick AC, Taylor R. Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects. Metabolism. 1996 Aug;45(8):947-50. doi: 10.1016/s0026-0495(96)90260-7.
Background: PubMed 21930939Kumashiro N, Erion DM, Zhang D, Kahn M, Beddow SA, Chu X, Still CD, Gerhard GS, Han X, Dziura J, Petersen KF, Samuel VT, Shulman GI. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16381-5. doi: 10.1073/pnas.1113359108. Epub 2011 Sep 19.
Background: PubMed 11739435Goodpaster BH, He J, Watkins S, Kelley DE. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab. 2001 Dec;86(12):5755-61. doi: 10.1210/jcem.86.12.8075.
Background: PubMed 21873552Amati F, Dube JJ, Alvarez-Carnero E, Edreira MM, Chomentowski P, Coen PM, Switzer GE, Bickel PE, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Diabetes. 2011 Oct;60(10):2588-97. doi: 10.2337/db10-1221. Epub 2011 Aug 26.
Background: PubMed 10690948Manco M, Mingrone G, Greco AV, Capristo E, Gniuli D, De Gaetano A, Gasbarrini G. Insulin resistance directly correlates with increased saturated fatty acids in skeletal muscle triglycerides. Metabolism. 2000 Feb;49(2):220-4. doi: 10.1016/s0026-0495(00)91377-5.
Background: PubMed 19615699Anastasiou CA, Kavouras SA, Lentzas Y, Gova A, Sidossis LS, Melidonis A. Diabetes mellitus is associated with increased intramyocellular triglyceride, but not diglyceride, content in obese humans. Metabolism. 2009 Nov;58(11):1636-42. doi: 10.1016/j.metabol.2009.05.019. Epub 2009 Jul 16.
Background: PubMed 19833891Coen PM, Dube JJ, Amati F, Stefanovic-Racic M, Ferrell RE, Toledo FG, Goodpaster BH. Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Diabetes. 2010 Jan;59(1):80-8. doi: 10.2337/db09-0988. Epub 2009 Oct 15.
Background: PubMed 20299618Bergman BC, Perreault L, Hunerdosse DM, Koehler MC, Samek AM, Eckel RH. Increased intramuscular lipid synthesis and low saturation relate to insulin sensitivity in endurance-trained athletes. J Appl Physiol (1985). 2010 May;108(5):1134-41. doi: 10.1152/japplphysiol.00684.2009. Epub 2010 Mar 18.
Background: PubMed 3292505King DS, Dalsky GP, Clutter WE, Young DA, Staten MA, Cryer PE, Holloszy JO. Effects of exercise and lack of exercise on insulin sensitivity and responsiveness. J Appl Physiol (1985). 1988 May;64(5):1942-6. doi: 10.1152/jappl.1988.64.5.1942.
Background: PubMed 21327867Dube JJ, Amati F, Toledo FG, Stefanovic-Racic M, Rossi A, Coen P, Goodpaster BH. Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide. Diabetologia. 2011 May;54(5):1147-56. doi: 10.1007/s00125-011-2065-0. Epub 2011 Feb 17.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Dana Dawson, MD principal investigator

University of Aberdeen Employee

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Training or detraining in people with Diabetes, run by University of Aberdeen at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Non-invasive 1H Magnetic Resonance Spectroscopy of vastus lateralis (time frame: One Hour). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03065140, which also lists 35 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2022.