Diabetes Interventional Assessment of Slimming or Training to Lessen Inconspicuous Cardiovascular Dysfunction

NCT02590822 | Recruiting

• 2 other identifiers: 0498182089
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

There is an epidemic of type 2 diabetes in younger adults. These patients are at very high lifetime risk of heart-related complications. Subtle heart abnormalities can be present even at a young age in these patients and may predispose them to heart failure and ultimately premature death. There is emerging evidence that type 2 diabetes can be reversed with weight loss. We propose that weight loss can also reverse the fatty changes seen in the liver and heart in these patients, and in turn lead to improved heart function. This project aims to identify how type 2 diabetes causes changes in the heart in young people with type 2 diabetes by performing detailed scans and other tests of the heart's structure and function. In addition we will attempt to see if the heart's pumping function can be improved, either by a weight loss program with a special low calorie diet, or by a structured program of exercise. This will be compared with the usual standard diabetes care. As well as looking to see if the heart's function can be improved with the intervention, we also aim to identify what the mechanism of any improvement would be. We suspect that changes in the amount of fat within the liver and the heart may be responsible, and will measure these at the beginning, end and in some patients halfway through the study to explore possible mechanisms amongst other clinical variables (e.g. HbA1c)

Conditions

Diabetes

Keywords

Diabetes; T2DM; young adults; heart; weight loss; MRI; exercise; diastolic function

Outcome Measures

Primary Outcomes (1)

• Increase in circumferential PEDSR rate as measured by CMR at 12 weeks.

  The aim of these analyses is to compare the primary outcome (diastolic strain rate) measured by CMR at 12 weeks between the TDR and standard care arms, and between the exercise and standard care arms. The primary analysis will be a per protocol analysis as this is a proof of principle study where we are primarily interested in the size of the treatment effect, rather than the practicability of the intervention.

  12 weeks

Secondary Outcomes (54)

• Left ventricular mass

  Baseline, 4 and 12 weeks

• End diastolic volume

  Baseline, 4 and 12 weeks

• End systolic volume

  Baseline, 4 and 12 weeks

• Ejection Fraction

  Baseline, 4 and 12 weeks

• LA Volumes

  Baseline, 4 and 12 weeks

Study Arms (3)

Standard Care

NO INTERVENTION

The Standard Care group will be contacted weekly (where possible) to reinforce cognitive behavioural adaptations and encourage compliance to diet and exercise. They will be provided with standard lifestyle advice according to NICE guidance.

Total Dietary Replacement

EXPERIMENTAL

Group receives a total meal replacement diet from Cambridge Weight Plan containing 810 kcal/day (40% protein, 50% carbohydrate, 10% fat). The diet will be stopped, and a maintenance diet re-introduced once 50% excess body weight has been lost, or by 12 weeks, whichever comes first. The TDR will be undertaken alongside health behaviour coaching and relapse prevention contact \& current medications will need to be adjusted initially and throughout the study.

Dietary Supplement: Cambridge Weight Plan

Supervised Exercise

EXPERIMENTAL

The exercise group will attend thrice weekly 60minute supervised exercise sessions at the Leicester-Loughborough Diet, Lifestyle and Physical Activity (LLP) BRU or at the Leicester Diabetes Centre. An initial assessment of cardiorespiratory fitness will be performed (VO2 max) to allow design of a tailored exercise programme. Current medication will need to be adjusted initially and throughout the study.

Other: Supervised Exercise Sessions

Interventions

Cambridge Weight Plan DIETARY_SUPPLEMENT

Group receives a total meal replacement diet from Cambridge Weight Plan containing 810 kcal/day (40% protein, 50% carbohydrate, 10% fat). As 3 or 4 mini-meals daily in flavoured formula food packets made up with water, milk or non-dairy alternative; or as snack bars based on preference. Supplemented with up to three portions of non-starchy vegetables and 2 litres of water, or other non-calorific drinks, per day. Participants to abstain from alcohol for study duration. The diet will be stopped, and a maintenance diet re-introduced once 50% excess body weight has been lost, or by 12 weeks, whichever comes first. The TDR will be undertaken alongside health behaviour coaching and relapse prevention through weekly, where possible, contact (telephone or face-to-face) with a qualified dietician or equivalent. Due to the potential risk of hypoglycaemia and symptomatic hypotension; medication at enrolment will need to be adjusted initially and throughout the study.

Total Dietary Replacement

Supervised Exercise Sessions OTHER

The exercise group will attend supervised exercise sessions at the Leicester-Loughborough Diet, Lifestyle and Physical Activity (LLP) BRU or at the Leicester Diabetes Centre. The exercise program will typically consist of a thrice weekly, 60 minute session of moderate intensity aerobic exercise, in line with prevailing guidelines. An initial assessment of cardiorespiratory fitness will be performed, and exercise intensity titrated to aim for a workload of approximately 60% of the patient's VO2 max. Due to the potential risk of hypoglycaemia and symptomatic hypotension; medication at enrolment will need to be adjusted initially and throughout the study.

Also known as: Physical Activity

Supervised Exercise

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capacity to provide informed consent before any trial-related activities
• Established T2DM (≥3months)
• HbA1c ≤ 9% if on triple therapy or ≤ 10% on diet \& exercise or monotherapy or dual therapy
• Current glucose lowering therapy either mono, dual or triple of any combination of metformin, sulphonylurea, DPP-IV inhibitor, GLP-1 therapy or an SGLT2 +/- diet and exercise
• Body mass index \> 30Kg/m2 or \> 27.5 Kg/m2 (South Asian),
• Diagnosis of T2DM before the age of 60 years of age
• Age ≥18 and ≤ 65 years

You may not qualify if:

• Diabetes duration \>12 years
• Currently taking more than three glucose lowering therapies
• Weight-loss of \>5kg in the preceding 6 months
• Stage 4 or 5 chronic kidney disease (eGFR\< 30ml/min/1.73m2),
• Current therapy with Insulin, thiazolidinediones, steroids or atypical antipsychotic medication
• Untreated thyroid disease
• Known macrovascular disease including coronary artery disease, stroke/TIA or peripheral vascular disease
• Presence of arrhythmia (including atrial fibrillation, atrial flutter, or 2nd or 3rd degree atrioventricular block)
• Known heart failure
• Other clinically relevant heart disease
• Inability to exercise or undertake a MRP
• Absolute contraindication to CMR
• Cardiovascular symptoms (angina, limiting dyspnoea during normal physical activity)
• Inflammatory condition e.g. Connective tissue disorder, Rheumatoid arthritis

Sponsors & Collaborators

• University of Leicester: lead
• University Hospitals, Leicester: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

Glenfield Hospital (University Hospitals of Leicester NHS Trust)

Leicester, LE3 9QP, United Kingdom

RECRUITING

Related Publications (8)

• Khan JN, Wilmot EG, Leggate M, Singh A, Yates T, Nimmo M, Khunti K, Horsfield MA, Biglands J, Clarysse P, Croisille P, Davies M, McCann GP. Subclinical diastolic dysfunction in young adults with Type 2 diabetes mellitus: a multiparametric contrast-enhanced cardiovascular magnetic resonance pilot study assessing potential mechanisms. Eur Heart J Cardiovasc Imaging. 2014 Nov;15(11):1263-9. doi: 10.1093/ehjci/jeu121. Epub 2014 Jun 26.

  PMID: 24970723 RESULT

• Brady EM, Cao TH, Moss AJ, Athithan L, Ayton SL, Redman E, Argyridou S, Graham-Brown MPM, Maxwell CB, Jones DJL, Ng L, Yates T, Davies MJ, McCann GP, Gulsin GS. Circulating sphingolipids and relationship to cardiac remodelling before and following a low-energy diet in asymptomatic Type 2 Diabetes. BMC Cardiovasc Disord. 2024 Jan 3;24(1):25. doi: 10.1186/s12872-023-03623-y.

  PMID: 38172712 DERIVED

• Athithan L, Gulsin GS, Henson J, Althagafi L, Redman E, Argyridou S, Parke KS, Yeo J, Yates T, Khunti K, Davies MJ, McCann GP, Brady EM. Response to a low-energy meal replacement plan on glycometabolic profile and reverse cardiac remodelling in type 2 diabetes: a comparison between South Asians and White Europeans. Ther Adv Endocrinol Metab. 2023 Oct 6;14:20420188231193231. doi: 10.1177/20420188231193231. eCollection 2023.

  PMID: 37811525 DERIVED

• Alfuhied A, Gulsin GS, Athithan L, Brady EM, Parke K, Henson J, Redman E, Marsh AM, Yates T, Davies MJ, McCann GP, Singh A. The impact of lifestyle intervention on left atrial function in type 2 diabetes: results from the DIASTOLIC study. Int J Cardiovasc Imaging. 2022 Sep;38(9):2013-2023. doi: 10.1007/s10554-022-02578-z. Epub 2022 Mar 2.

  PMID: 35233724 DERIVED

• Walters GWM, Redman E, Gulsin GS, Henson J, Argyridou S, Yates T, Davies MJ, Parke K, McCann GP, Brady EM. Interrelationship between micronutrients and cardiovascular structure and function in type 2 diabetes. J Nutr Sci. 2021 Oct 4;10:e88. doi: 10.1017/jns.2021.82. eCollection 2021.

  PMID: 34733500 DERIVED

• Gulsin GS, Swarbrick DJ, Athithan L, Brady EM, Henson J, Baldry E, Argyridou S, Jaicim NB, Squire G, Walters Y, Marsh AM, McAdam J, Parke KS, Biglands JD, Yates T, Khunti K, Davies MJ, McCann GP. Effects of Low-Energy Diet or Exercise on Cardiovascular Function in Working-Age Adults With Type 2 Diabetes: A Prospective, Randomized, Open-Label, Blinded End Point Trial. Diabetes Care. 2020 Jun;43(6):1300-1310. doi: 10.2337/dc20-0129. Epub 2020 Mar 27.

  PMID: 32220917 DERIVED

• Gulsin GS, Brady EM, Swarbrick DJ, Athithan L, Henson J, Baldry E, McAdam J, Marsh AM, Parke KS, Wormleighton JV, Levelt E, Yates T, Bodicoat D, Khunti K, Davies MJ, McCann GP. Rationale, design and study protocol of the randomised controlled trial: Diabetes Interventional Assessment of Slimming or Training tO Lessen Inconspicuous Cardiovascular Dysfunction (the DIASTOLIC study). BMJ Open. 2019 Mar 30;9(3):e023207. doi: 10.1136/bmjopen-2018-023207.

  PMID: 30928925 DERIVED

• Gulsin GS, Swarbrick DJ, Hunt WH, Levelt E, Graham-Brown MPM, Parke KS, Wormleighton JV, Lai FY, Yates T, Wilmot EG, Webb DR, Davies MJ, McCann GP. Relation of Aortic Stiffness to Left Ventricular Remodeling in Younger Adults With Type 2 Diabetes. Diabetes. 2018 Jul;67(7):1395-1400. doi: 10.2337/db18-0112. Epub 2018 Apr 16.

  PMID: 29661781 DERIVED

Related Links

• Leicester Diabetes Centre

MeSH Terms

Conditions

Diabetes Mellitus; Weight Loss; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Gerry Dr McCann, MD

  University of Leicester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gerry P McCann, MD

CONTACT

0116 258; Gerry.McCann@uhl-tr.nhs.uk

Emer Brady, PhD

CONTACT

0116 258; emer.brady@uhl-tr.nhs.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2015
• First Posted: October 29, 2015
• Study Start: October 2, 2015
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: January 5, 2024

Record last verified: 2024-01

Locations

GB (1)