Using Pharmacogenetics to Improve Treatment in Early-onset Diabetes

NCT01238380 | Completed DMC

• 2 other identifiers: REC 10/H0106/63HICF-1009-041
• Study Type: observational
• Target: 1,916
• Locations: 1 country
• Sites: 3

Brief Summary

Monogenic diabetes is an unusual form of diabetes. It usually presents in patients under the age of 30, so is often misdiagnosed as Type 1 diabetes which is more common. Patients with monogenic diabetes can often be treated with tablets rather than insulin injections, leading to better control of their diabetes, and fewer side-effects and complications. Less than 5% of people with monogenic diabetes in the UK have been identified, meaning up to 20,000 patients may still be misdiagnosed and receiving inappropriate treatment. We want to identify the best way of ensuring that people diagnosed with diabetes under the age of 30 have all the necessary tests to ensure they have the correct treatment for their particular type of diabetes. A small number of people may, as part of this study, be found to have a specific genetic cause of their diabetes and in these cases we will measure the success and benefits of changing their treatment, usually from insulin injections to sulphonylurea tablets.

Conditions

Diabetes

Keywords

Monogenic diabetes; HNF1A; HNF4A; GCK; genetic testing; health economic model

Outcome Measures

Primary Outcomes (1)

• Identification of patients with monogenic diabetes

  The aim of this project is to identify the prevalence of patients with monogenic diabetes resulting from mutations in the HNF1A/HNF4A/GCK genes, amongst patients with early-onset diabetes, diagnosed less than 30 years.

  Within 4 years from start of project

Secondary Outcomes (2)

• To examine the impact of making a diagnosis of monogenic diabetes on patients' treatment, glucose control and quality of life.

  Within 4 years of the project start date.

• To develop a health economic model of the care pathway leading to testing of monogenic diabetes.

  Within 4 years of the project start date.

Study Arms (1)

Diabetes diagnosed under 30 years

Patients currently under 50 years of age diagnosed with diabetes under 30 years.

Other: patient care pathway

Interventions

patient care pathway OTHER

Stage 1: Urinary c-peptide creatinine ratio (UCPCR); if positive progress to Stage 2. Stage 2: Pancreatic auto-antibodies measurement (GAD65 \& IA2); if negative progress to genetic testing. Genetic testing for HNF1A, HNF4A, GCK. If positive, progress to Stage 3. Stage 3: review and potential change of diabetes treatment. Monitor success via use of three standardised health and quality of life questionnaires and Hba1c pre-treatment change and at 1, 3, 6 and 12 months post-treatment change.

Diabetes diagnosed under 30 years

Eligibility Criteria

• Age: Up to 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients currently under the age of 50 years, diagnosed under the age of 30years, from South-West England and Tayside, Scotland, UK.

You may qualify if:

• clinical diagnosis of diabetes
• diagnosed under 30 years of ages
• current age less than 50 years
• willing and able to provide informed consent.

You may not qualify if:

• age over 50 years
• age at diagnosis over 30 years
• adult with incapacity to consent
• child with incapacity to assent

Sponsors & Collaborators

• University of Exeter: lead
• University of Dundee: collaborator
• Wellcome Trust: collaborator
• Department of Health, United Kingdom: collaborator

Study Sites (3)

Peninsula NIHR Clinical Research Facility, Peninsula Medical School, Barrack Rd,

Exeter, Devon, EX2 5DW, United Kingdom

Location

Peninsula College of Medicine & Dentistry, University of Plymouth, John Bull Building, Tamar Science Park,

Plymouth, Devon, PL6 8BU, United Kingdom

Location

Biomedical Research Institute, University of Dundee,

Dundee, DD1 9SY, United Kingdom

Location

Related Publications (9)

• Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, Ellard S. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia. 2010 Dec;53(12):2504-8. doi: 10.1007/s00125-010-1799-4. Epub 2010 May 25.

  PMID: 20499044 BACKGROUND

• McDonald TJ, Knight BA, Shields BM, Bowman P, Salzmann MB, Hattersley AT. Stability and reproducibility of a single-sample urinary C-peptide/creatinine ratio and its correlation with 24-h urinary C-peptide. Clin Chem. 2009 Nov;55(11):2035-9. doi: 10.1373/clinchem.2009.129312. Epub 2009 Aug 27.

  PMID: 19713273 BACKGROUND

• Shepherd M, Shields B, Ellard S, Rubio-Cabezas O, Hattersley AT. A genetic diagnosis of HNF1A diabetes alters treatment and improves glycaemic control in the majority of insulin-treated patients. Diabet Med. 2009 Apr;26(4):437-41. doi: 10.1111/j.1464-5491.2009.02690.x.

  PMID: 19388975 BACKGROUND

• Ellard S, Bellanne-Chantelot C, Hattersley AT; European Molecular Genetics Quality Network (EMQN) MODY group. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia. 2008 Apr;51(4):546-53. doi: 10.1007/s00125-008-0942-y. Epub 2008 Feb 23.

  PMID: 18297260 BACKGROUND

• Pearson ER, Pruhova S, Tack CJ, Johansen A, Castleden HA, Lumb PJ, Wierzbicki AS, Clark PM, Lebl J, Pedersen O, Ellard S, Hansen T, Hattersley AT. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection. Diabetologia. 2005 May;48(5):878-85. doi: 10.1007/s00125-005-1738-y. Epub 2005 Apr 14.

  PMID: 15830177 BACKGROUND

• Pearson ER, Starkey BJ, Powell RJ, Gribble FM, Clark PM, Hattersley AT. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet. 2003 Oct 18;362(9392):1275-81. doi: 10.1016/S0140-6736(03)14571-0.

  PMID: 14575972 BACKGROUND

• Grace SL, Cooper A, Jones AG, McDonald TJ. Zinc transporter 8 autoantibody testing requires age-related cut-offs. BMJ Open Diabetes Res Care. 2021 Aug;9(1):e002296. doi: 10.1136/bmjdrc-2021-002296.

  PMID: 34348918 DERIVED

• Peters JL, Anderson R, Shields B, King S, Hudson M, Shepherd M, McDonald TJ, Pearson E, Hattersley A, Hyde C. Strategies to identify individuals with monogenic diabetes: results of an economic evaluation. BMJ Open. 2020 Mar 18;10(3):e034716. doi: 10.1136/bmjopen-2019-034716.

  PMID: 32193268 DERIVED

• Shields BM, Shepherd M, Hudson M, McDonald TJ, Colclough K, Peters J, Knight B, Hyde C, Ellard S, Pearson ER, Hattersley AT; UNITED study team. Population-Based Assessment of a Biomarker-Based Screening Pathway to Aid Diagnosis of Monogenic Diabetes in Young-Onset Patients. Diabetes Care. 2017 Aug;40(8):1017-1025. doi: 10.2337/dc17-0224.

  PMID: 28701371 DERIVED

Related Links

• website providing information regarding monogenic diabetes

Biospecimen

Retention: SAMPLES WITH DNA

Samples with DNA and plasma samples.

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Andrew T Hattersley

  Peninsula NIHR Clinical Research Facility, Peninsula Medical School, University of Exeter, Barrack Rd, Exeter, EX2 5DW

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2010
• First Posted: November 10, 2010
• Study Start: December 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: March 19, 2019

Record last verified: 2019-03

Locations

GB (3)