StartRight: Getting the Right Classification and Treatment From Diagnosis in Adults With Diabetes

Study Overview
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Brief Summary
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This study aims to achieve more accurate early classification of diabetes and identification of which patients will rapidly require insulin treatment. The investigators will recruit 1200 participants who have been diagnosed with diabetes in the last year and were aged between 18 and 50 years at the time of diagnosis. The investigators will recruit an additional cohort of 800 participants diagnosed after age 50. The investigators will record clinical features and biomarkers that may help us to determine diabetes type at diagnosis and follow participants for 3 years to assess the development of severe insulin deficiency (measured using C-peptide) and insulin requirement. The investigators will assess utility of clinical features and additional biomarkers in identifying patients with rapid progression to insulin requirement. Findings will be integrated into a freely available clinical prediction models to assist classification of diabetes at diagnosis.

Detailed Description
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The study is a prospective observational study which will assess the relationship between clinical features and biomarkers at diabetes diagnosis and type of diabetes defined by endogenous insulin secretion at 3 years diabetes duration. The investigators will recruit a prospective cohort of 1200 adults that have been diagnosed with diabetes within the previous 1 year and aged between 18 and 50 at the time of diagnosis. The investigators will also recruit an additional cohort of 800 participants diagnosed with diabetes in the last year aged >50 at diabetes diagnosis, who will be stratified by insulin treatment (insulin treated n=400). On recruitment into the study, non-fasting (within 1-5 hours of a meal) blood sample will be collected for baseline analysis biomarker assessment (serum C-peptide, routine biochemistry, Islet autoantibodies (GAD, IA2, ZnT8)) and biobanking. Clinical features will be recorded, including weight, height, waist/hip ratio & blood pressure. Participants will be asked to provide a home post-meal urine sample for Urinary C-Peptide Creatinine Ratio (UCPCR). At 1 year and 2 years post recruitment, participants will be contacted by telephone, email or in person to record concurrent treatment, hypoglycaemia and health service utilisation. Participants will be asked to collect a home post-meal urine sample for Urinary C-Peptide /Creatinine Ratio (UCPCR). HbA1c results will be obtained from participants GP practice or laboratory records. At the end of the study, 3 years post recruitment, a non-fasting blood sample will be collected for serum C-peptide, routine biochemistry and stored for future biomarker analysis. Weight change, blood pressure, concurrent treatment, hypoglycaemia and health service utilisation data will be also be recorded.

Official Title
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StartRight: Getting the Right Classification and Treatment From Diagnosis in Adults With Diabetes

Conditions
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Diabetes Mellitus

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults diagnosed with diabetes within the previous 12 months. Aged ≥18 and ≤50 at the time of diabetes diagnosis* or (additional late onset diabetes cohort) aged >50 at the time of diabetes diagnosis. Able and willing to provide informed consent Exclusion Criteria: Gestational diabetes. Known secondary diabetes (diabetes considered likely due to medication, cystic fibrosis, pancreatitis, pancreatic cancer, pancreatic surgery, hemochromatosis or Cushing's syndrome).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1 Age 18-50 at diagnosis<br>Diagnosed with diabetes within the previous 1 year. Aged between 18 and 50 years at the time of diabetes diagnosis | |
| Group 2 Late Onset (insulin)<br>Diagnosed with diabetes within the previous 1 year. Aged >50 at the time of diabetes diagnosis and treated with insulin therapy | |
| Group 3 Late Onset (no insulin)<br>Diagnosed with diabetes within the previous 1 year. Aged >50 at the time of diabetes diagnosis and treated without insulin | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diabetes type defined by insulin requirement at 3 years | Type 1 diabetes = Progression to insulin treatment and severe insulin deficiency (post meal plasma C-peptide <600pmol/L) at 3 years. Type 2 diabetes = Lack of requirement for insulin at 3 years (HbA1c <90mmol/mol without insulin treatment or post meal C-peptide ≥ 600pmol/L if insulin treated). | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stimulated plasma C-peptide <200pmol/L at 3 years ('absolute insulin deficiency') | C-peptide <200pmol/L at 3 years = absolute insulin deficiency | 3 years | 
| C-peptide rate of change (UCPCR and plasma) | The rate of change of UCPCR and plasma C-peptide | 3 years | 
| Weight change (baseline to 3 years) | Assessment of weight change from baseline to 3 year visit | 3 years | 
| HbA1c (mean and at 3 years) | Mean HbA1c for all visits and result at 3 years | 3 years | 
| Self-reported hypoglycaemia & hypoglycaemic awareness (Modified Clark and Gold) | Results from Hypoglycaemia questionnaire | 3 years | 
| Resilience (CD-RISC questionnaires) | Results from analysis of data from CD-RISC questionnaire | 3 years | 
| Ketoacidosis (self-reported and confirmed from medical notes) | Self reported Ketoacidosis and confirmation in medical notes | 3 years | 
| Wellbeing (SF12 questionnaire) | Results from analysis of data from SF12 questionnaire | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, C-peptide, Insulin, Classification