The StartRIGHT Pilot Study; Getting the Right Classification and Treatment From Diagnosis in Adults With Diabetes

Diabetes is stratified into recognised subtypes with major implications for patients' treatment. The treatment of Type 1 diabetes (T1D), Type 2 diabetes (T2D) and Maturity-onset diabetes of the young (MODY) is markedly different and based on clear differences in underlying pathophysiology. The difficult part of this stratification is correctly diagnosing the subtype especially in young adults. The clear differentiation of T1D as slim and young, and T2D as obese and old, no longer holds with the rapid increase in obesity in the population: T1D patients may be obese and T2D patients may be diagnosed young. 90% of MODY patients are misdiagnosed with T1D or T2D as the diagnosis of MODY is rarely considered. This results in 7-15% of young adults with diabetes being wrongly classified and incorrectly treated. Initial clinical diagnosis is not systematic and once made is rarely changed. Misdiagnosis of T2D or MODY as T1D results in unnecessary initial insulin treatment leading to higher drug/monitoring costs, more side effects (weight gain, hypos), and patient inconvenience/dissatisfaction. Misdiagnosis of T1D as T2D, or MODY (initial treatment diet/tablets), results in poor glycaemic control, frequent contact for increased treatment, inappropriate insulin regimes and the risk of life threatening ketoacidosis.

The investigators have developed an optimized diagnostic strategy (ODS) based on integrating Clinical information (a validated clinical probability model), Biomarkers (GAD, Islet antigen-2 (IA2) and ZnT8 autoantibodies) and Genetic testing for MODY. This has the potential to determine the subtype of diabetes in young adults leading to improved treatment and care. Prior to undertaking a comprehensive RCT to test our ODS against standard care, the investigators must first undertake this pilot study to assess the feasibility of such a project.

Objectives: To assess the feasibility of recruitment and retention for a proposed large scale RCT, optimize recruitment and retention strategies, develop and assess the protocols and procedures, test delivery of the ODS, assess the impact of the ODS and obtain pilot data to inform sample size calculations for the proposed RCT Potential participants will be identified from routine clinical care, with clinicians informing patients of the project in general terms and seeking permission for their contact details to be passed to the research team. A range of referral strategies will be assessed and all potential participants who appear to meet the entry criteria will be invited to participate.

Referral strategies to be assessed will include: referral to research team by GP/ Practice Nurse/diabetes specialist nurse, regular GP practice database searches, via pathology lab following raised Hba1c Initial visit (I hour): Participants will meet with a member of the research team who will obtain consent and collect baseline blood samples, demographic and QoL data. Participants will be randomised to either the intervention or control arm using a computer generated randomisation schedule. For participants in the intervention arm the blood samples will be analysed at the Royal Devon &Exeter National Health Service Foundation Trust (RD&E NHS FT) Biochemistry Department for HbA1c, C-peptide and islet autoantibodies (GAD, IA2 and ZnT8) with DNA extracted and stored for genetic testing if appropriate. These blood results will then be immediately incorporated into the ODS for feedback to Clinicians and participants with recommendations that appropriate national guidelines for the ODS diagnosis (e.g. NICE guidelines for Type 1 or Type 2 diabetes) are followed. For participants in the control arm their current clinical features will be recorded and their blood samples will be stored for future analysis. At the end of their involvement in the study, both recorded clinical features and results from stored blood samples will then be and incorporated into the ODS for feedback to both clinicians and participant.

Follow up (6 monthly intervals over 3 years): Participants will then be followed up at 6 monthly intervals over a 3 year period (choice given of text, phone, or email) to maintain participant engagement and enable collection of details of current treatment, treatment changes and frequency of hypoglycaemia. Results from routinely collected HbA1cs will be obtained from clinical practice.