Type 2 diabetes in childhood: building a platform to support novel intervention strategies

Lead Research Organisation: University of Birmingham
Department Name: Clinical and Experimental Medicine

Abstract

The rise in childhood obesity has led to children developing obesity related type 2 diabetes, something that was never seen in the UK 20 years ago. We know that these children will get serious cardiovascular disease in adulthood; but we do not know what are the best treatments to prevent or delay the onset to these diseases. This proposal is to establish a UK national cohort of children with type 2 diabetes, carefully characterised, so that they can be involed in clinical trials of treatments to improve their outcomes.

Technical Summary

Obesity related Type 2 diabetes now occurs in children; we described the first UK cases in 2000 (Ehtisham S et al 2000) and shown that there are approximately 70 new cases a year under 17 completed years in the UK (Haines L et al 2007). There is a minimal evidence base for treatment of childhood type 2 diabetes, and children are not included in the NICE guidelines on the management of type 2 diabetes in the UK. We propose to establish a national cohort of children with type 2 diabetes. The purposes are to develop a tightly characterized cohort for intervention with clinical trials that will develop the evidence base for treatment; and to determine the natural history of type 2 diabetes in a UK population diagnosed in childhood.

Publications

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Candler TP (2018) Continuing rise of Type 2 diabetes incidence in children and young people in the UK. in Diabetic medicine : a journal of the British Diabetic Association

 
Guideline Title NICE Guideline on management of childhood diabetes
Description Influence on revision to NICE guidelines on management of diabetes in children
Geographic Reach National 
Policy Influence Type Citation in clinical guidelines
 
Guideline Title ISPAD Guidelines on management of childhood diabetes
Description Input into international guideline on childhood type 2 diabetes
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical guidelines
 
Description NIHR Bioresource for translational research in common and rare diseaess
Amount £425,000 (GBP)
Organisation NIHR Rare Diseases Translational Research Collaboration (RD-TRC) 
Sector Public
Country Unknown
Start 11/2017 
End 03/2022
 
Description NIHR TRC Rare Diseases Patient Cohorts round 1
Amount £320,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 11/2013 
End 03/2015
 
Description Research grant scheme/European Foundation for the Study of Diabetes
Amount £250,000 (GBP)
Organisation European Association for the Study of Diabetes (EASD) 
Department European Foundation for the Study of Diabetes (EFSD)
Sector Charity/Non Profit
Country Germany
Start 09/2010 
End 08/2012
 
Title NIHR Bioresource for Translational Research in Common and Rare Diseases 
Description The UK national cohort of childhood type 2 diabetes and cohort of Wolfram patients has been adopted by the NIHR Bioresource. This means participants are consenting to joining a recallable database of patients willing to share their medical information, provide a standardised blood sample stored in the NIHR Biosample Centre in Milton Keynes, and be contacted for future studies 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact This is part of a national initiative 
URL https://bioresource.nihr.ac.uk
 
Description Academic: EASD 
Organisation European Association for the Study of Diabetes (EASD)
Country European Union (EU) 
Sector Charity/Non Profit 
PI Contribution Co-applicant on grant, but not CI. Recruited patients from MRC patient cohort
Collaborator Contribution None
Impact Currently in write-up
Start Year 2010
 
Description Commercial - Merck Sharpe Dohme 
Organisation Merck
Country Germany 
Sector Private 
PI Contribution The title of the clinical trial is: A Phase III, Multicenter, Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-0431A (A Fixed-Dose Combination Tablet of Sitagliptin and Metformin) in Pediatric Patients with Type 2 Diabetes Mellitus from MRC cohort to phase III study. Our team has recruited the first UK patients to this study from the MRC patient cohort
Collaborator Contribution Our partners (n=60) are investigating their recruits to the MRC patient cohorts to identify other eligible children.
Impact Recruitment commenced, first patients in the UK, from the MRC patient cohort. Closed to recruitment Sept 2018. Awaiting results meeting
Start Year 2011
 
Description Commercial - Novo Nordisk 
Organisation Novo Nordisk
Country Denmark 
Sector Public 
PI Contribution Study title: Effect of Liraglutide in combination with metformin versus metformin mono therapy on glycaemic control in children and adolescents with type 2 diabetes; a 14 week double-blind, randomised, parallel group, placebo controlled multi-venter study followed by a 38 week open label extension. Screening of patients from MRC patient cohort for recruitment to this phase III study
Collaborator Contribution Our 60 NHS partners who have been recruiting to the MRC patient cohort, have been screening their local patients for children eligible to this study.
Impact Screening and Recruitment was completed in March 2018. The study results (Ellipse study) were announced in January 2019. A manuscript is in preparation. Currently an abstract has been accepted for the Paediatric Endocrine Society. This is really exciting as it is the first clinical trial to show efficacy of a new treatment for type 2 diabetes in 17 years Abstract Title: The efficacy and safety of liraglutide versus placebo in children and adolescents with type 2 diabetes: the ELLIPSE randomized trial results
Start Year 2012
 
Description Commercial - Sanofi Aventis 
Organisation Sanofi
Department Aventis
Country France 
Sector Private 
PI Contribution Recruitment from MRC patient cohort to phase III study
Collaborator Contribution recruitment of patients
Impact Study on hold
Start Year 2012
 
Description Commercial: clinical study Bristol Myers Squibb 
Organisation Bristol-Myers Squibb
Country United States 
Sector Private 
PI Contribution Recruitment from MRC patient cohort to Phase III study
Collaborator Contribution Ditto
Impact Study terminated by company
Start Year 2012
 
Description Liraglutide Phase 2 trial 
Organisation Novo Nordisk
Country Denmark 
Sector Public 
PI Contribution Chief UK Investigator for the UK sites. Input into the protocol. Recruitment of patients from the MRC Patient Cohorts study of type 2 diabetes in children.
Collaborator Contribution Support for phase II clinical trial of the GLP-1 agonist Liraglutide
Impact Results have been published and added to publication record
Start Year 2010
 
Description Interview for BBC Panorama 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interview with a patient on BBC Panorama Youtube link below


https://youtu.be/dIwEiHAUyhc
Year(s) Of Engagement Activity 2017
 
Description Parent support group meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact I presented this study to our parent group at which there were 30 families with diabetes. I had interest from those families with children affected by type 2 diabetes.

Families were relieved to know that there was research going on in their child's disease area.
Year(s) Of Engagement Activity 2010
 
Description Pharmacologic approaches to the management of type 2 diabetes in children 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Third sector organisations
Results and Impact Presentation to national audience at Diabetes UK Annual Professional Conference
Year(s) Of Engagement Activity 2016
 
Description Presentation to Finnish Paediatric Diabetes Association 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Raising awareness and description of UK population with childhood type 2 diabetes
Year(s) Of Engagement Activity 2019
 
Description Presentation to Novo Nordisk global expert panel on childhood type 2 diabetes 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation developed to highlight the rapid progression of childhood type 2 diabetes compared with adult diabetes
Year(s) Of Engagement Activity 2016
 
Description Presentation to South Asian Health Foundation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This alerted delegates to the fact that type 2 diabetes disproportionately affects children from South Asian communities and black communities

Greater awareness of the issues
Year(s) Of Engagement Activity 2012
 
Description Presentation to industry and national health professionals - Servier meeting, Paris 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Presentation to raise awareness in industry of the problem of childhood type 2 diabetes
Year(s) Of Engagement Activity 2017
 
Description Presentation to international audience, International Society for Paediatric and Adolescent Diabetes (ISPAD) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation and question and answer session at international conference
Year(s) Of Engagement Activity 2016
 
Description Presentations at Novo Nordisk results meeting for Ellipse study 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation on background to childhood type 2 diabetes, case presentations
Year(s) Of Engagement Activity 2018,2019
 
Description Talk to South Asian Health Foundation - type 2 diabetes and the young 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation on findings of UK national cohort
Year(s) Of Engagement Activity 2016
 
Description Talk to Welsh paediatric diabetes group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Presentation of type 2 diabetes to national group
Year(s) Of Engagement Activity 2018
 
Description Type 2 diabetes : child and adult perspectives 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Joint presentation with colleague from adult medicine on problem of childhood type 2 diabetes
Year(s) Of Engagement Activity 2017
 
Description UK Chief Investigator talk for Astra Zeneca at clinical trial commencement meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation of issue of childhood diabetes to international health professional audience
Year(s) Of Engagement Activity 2017
 
Description Update on childhood type 2 diabetes 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact This was a presentation at the Diabetes UK annual professional and patient conference, attended by many members affected by diabetes

There was a lot of interest generated in the development of type 2 diabetes in young people
Year(s) Of Engagement Activity 2012