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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes Mellitus

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 1815

Contacts and Locations

Study Locations

• United Kingdom
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Anita Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Recently diagnosed diabetes patients in primary care, secondary care or community.

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1 Age 18-50 at diagnosis; 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); 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); 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?

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

Collaborators and Investigators

• Sponsor: Royal Devon and Exeter NHS Foundation Trust
• Collaborators: National Institute for Health Research, United Kingdom; University of Exeter; Diabetes UK
• Investigators: Principal Investigator: Angus G Jones, MBBS MRCP, Royal Devon & Exeter NHS Foundation Trust & University of Exeter

Publications and helpful links

General Publications

• Thomas NJ, Lynam AL, Hill AV, Weedon MN, Shields BM, Oram RA, McDonald TJ, Hattersley AT, Jones AG. Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes. Diabetologia. 2019 Jul;62(7):1167-1172. doi: 10.1007/s00125-019-4863-8. Epub 2019 Apr 10.
• Eason RJ, Thomas NJ, Hill AV, Knight BA, Carr A, Hattersley AT, McDonald TJ, Shields BM, Jones AG; StartRight Study Group. Routine Islet Autoantibody Testing in Clinically Diagnosed Adult-Onset Type 1 Diabetes Can Help Identify Misclassification and the Possibility of Successful Insulin Cessation. Diabetes Care. 2022 Dec 1;45(12):2844-2851. doi: 10.2337/dc22-0623.
• Thomas NJ, Hill AV, Dayan CM, Oram RA, McDonald TJ, Shields BM, Jones AG; StartRight Study Group. Age of Diagnosis Does Not Alter the Presentation or Progression of Robustly Defined Adult-Onset Type 1 Diabetes. Diabetes Care. 2023 Jun 1;46(6):1156-1163. doi: 10.2337/dc22-2159.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Estimated): October 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: October 8, 2018
• First Submitted That Met QC Criteria: November 7, 2018
• First Posted (Actual): November 13, 2018

Study Record Updates

• Last Update Posted (Actual): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 4, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Diabetes; Insulin; Classification; C-peptide
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus
• Other Study ID Numbers: CRF243; 203567 (Other Identifier: IRAS); CS-2015-15-018 (Other Grant/Funding Number: NIHR); 17/0005624 (Other Grant/Funding Number: Diabetes UK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No