Hybrid closed loop insulin pumps and early worsening of diabetic retinopathy in Type 1 diabetes
| ISRCTN | ISRCTN11740459 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11740459 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Integrated Research Application System (IRAS) | 349443 |
| Protocol serial number | CPMS 65120 |
| Sponsor | University of Liverpool |
| Funders | Breakthrough T1D UK, Novo Nordisk UK Research Foundation, University Hospitals of Liverpool Charity |
- Submission date
- 10/11/2025
- Registration date
- 22/12/2025
- Last edited
- 22/12/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
People with type 1 diabetes need insulin to control their blood sugar levels. New technologies called hybrid closed loop (HCL) insulin pumps, sometimes called “artificial pancreas” systems, automatically adjust insulin delivery using continuous glucose monitoring. These systems help people achieve much tighter glucose control.
However, when blood sugar levels improve very quickly, there can sometimes be a temporary worsening of eye disease known as early worsening of diabetic retinopathy (EWDR). This effect has been seen in the past when diabetes treatment was intensified, but it is not known how often it happens with new HCL systems.
The INSIGHT 1 study will follow people with type 1 diabetes who are starting on HCL insulin systems and compare them with people who continue using multiple daily insulin injections (MDI) or stand alone (open loop) pumps.
Who can participate?
Anyone with type 1 diabetes who is within 28 days of starting a HCL system or anyone who chooses to remain on MDI or open loop insulin pumps
What does the study involve?
Participants will have detailed eye examinations including:
1. Retinal photographs and optical coherence tomography (OCT) scans to achieved detailed 2D and 3D pictures of the back of the eye
2. Electroretinography (ERG) to measure how the nerves around the retina function
3. Blood samples to look for biological markers (such as growth factors and inflammation) which may be implicated in EWDR
What are the possible benefits and risks of participating?
The only direct benefit from this study would be the identification of a previously unknown health problem whose prompt treatment may improve your health. We don’t envisage there to be any significant risks of taking part. The knowledge gained from this study may affect the tests and structure of clinic appointments employed in the future that aim to assess the eye-health needs of people with type 1 diabetes who are started on hybrid closed loop technologies.
Where is the study run from?
The study will take place at St Paul’s Eye Unit, Royal Liverpool Hospital, University Hospitals of Liverpool Group, Liverpool, UK
When is the study starting and how long is it expected to run for?
The study started recruiting in May 2025 and we envisage recruitment to end in July 2027. We envisage the end of study visits to be July 2028 and the data collection to be July 2029.
Who is funding the study?
This study is jointly funded by Breakthrough T1D and the Novo Nordisk UK Research Foundation, with support for reading of the images provided by a University Hospitals of Liverpool Charity Grant.
Who is the main contact?
Please contact Dr Matthew Anson (manson1@liverpool.ac.uk) for any queries
Contact information
Public, Scientific
Institute of Life Course and Medical Sciences
University of Liverpool
William Henry Duncan Building
6 West Derby Street
Liverpool
L7 8TX
United Kingdom
| Phone | +44 (0)151 529 5917 |
|---|---|
| manson1@liverpool.ac.uk |
Principal investigator
Clinical Sciences Centre
University Hospital Aintree
Longmoor Lane
Liverpool
L9 7AL
United Kingdom
| Phone | +44 (0)151 529 5917 |
|---|---|
| ualam@liverpool.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Study design | Prospective non-interventional cohort study |
| Secondary study design | Cohort study |
| Study type | Participant information sheet |
| Scientific title | Evaluating the association between hybrid closed-loop insulin pump therapy and early worsening of diabetic retinopathy in adults with Type 1 diabetes over a 24-month period: a prospective cohort comparison with multiple daily injections or stand-alone CSII |
| Study acronym | INSIGHT-1 |
| Study objectives | The aim of INSIGHT-1 is to evaluate whether HCL insulin delivery is associated with development of EWDR, and to gain mechanistic insights into the condition. |
| Ethics approval(s) |
Approved 02/12/2024, London - Harrow Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 1048 154; harrow.rec@hra.nhs.uk), ref: 24/PR/1353 |
| Health condition(s) or problem(s) studied | Type 1 diabetes |
| Intervention | All participants will undergo digital colour fundoscopy, optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), electroretinography (ERG), routine blood tests, additional blood tests for inflammatory cytokines, height and weight measurement, measurement of visual acuity and undertake an eye health questionnaire. These assessments will be done at baseline, and repeat and 3, 6 and 12 months. A virtual review of health records will be conducted at 24 months. |
| Intervention type | Other |
| Primary outcome measure(s) |
The rate of early worsening of diabetic retinopathy (EWDR) in individuals who are newly initiated on a hybrid closed loop insulin pump (HCL). EWDR will be defined as either: |
| Key secondary outcome measure(s) |
1. The rate of one-step change in ETDRS (baseline vs 3 months; baseline vs 6 months; baseline vs 12 months) |
| Completion date | 04/08/2029 |
Eligibility
| Participant type(s) | Population |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | All |
| Target sample size at registration | 203 |
| Key inclusion criteria | HCL group: 1. Able to attend screening visit within 28 days of initiation on a HCL 2. Baseline HbA1c ≥58 mmol/mol Control group: 1. Does not meet the national criteria for HCL initiation (MDI or stand alone/open loop insulin pump) |
| Key exclusion criteria | 1. Pregnancy. This is because pregnancy is an established risk factor for EWDR and would be a significant confounding variable 2. Unable to give informed consent 3. Type 2 diabetes, MODY, cystic fibrosis related diabetes, other secondary causes of diabetes |
| Date of first enrolment | 07/05/2025 |
| Date of final enrolment | 31/07/2027 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
St Paul's Eye Unit
Lower Ground Floor
Liverpool
L7 8YE
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available in an anonymised format upon request (contact Dr Matthew Anson, manson1@liverpool.ac.uk) |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
11/11/2025: Study's existence confirmed by the HRA.
