Diabetes Alliance for Research in England (DARE) (Previously EXTRA)

Both major types of diabetes (Type 1 and Type 2) represent classical “complex disorders” with both genetic and environmental factors playing an important role. There is considerable evidence that genetic factors are important in the development of diabetes. Evidence for this includes the clustering of disease in families, a high concordance rate in identical twins and migration studies. However, the majority of Type 2 forms of diabetes are greatly influenced by environment as shown by the rapidly increasing prevalence in the last two decades. This does not represent an alteration in the population gene frequency but rather changes in the environment, specifically a reduction in physical activity and increased food consumption.

Diabetes is a major cause of morbidity and mortality and has been estimated to account for 10% of NHS spending and this is likely to increase. Therefore, understanding how the disease develops, progresses over time and how to prevent complications is a major health priority.

GP patient data shows that there are now 4.05 million people with diabetes in the UK, which includes 3.5 million adults who have been diagnosed, an increase of 119,965 compared to the previous year, and an increase of 65%. There are also thought to be 549,000 people with undiagnosed Type 2 diabetes [Quality and Outcomes Framework, Health and Social Care Information Centre, Information Services Division Scotland. Statistics for Wales, Department of Health, Social Services and Public Safety, 2014 – 2015].

The prevalence of diabetes is estimated to rise to 4 million by 2025 and the current cost of diabetes to the NHS is over £1.5m an hour or 10% of the NHS budget for England and Wales. This equates to over £25,000 being spent on diabetes every minute. In total, an estimated £14 billion pounds is spent a year on treating diabetes and its complications, with the cost of treating complications representing the much higher cost (http://www.diabetes.co.uk/cost-of-diabetes.html).

The Diabetes Alliance for Research in England (DARE) study, is an observational, prospective cohort study. The study was set up in 2007 to establish an epidemiologically based sample of patients with diabetes (Diabetes group) and those without (Control group), within the Exeter region. Participants were recruited in the Exeter region and the data requested relates to these participants rather than the full nationwide cohort. The Royal Devon University Healthcare NHS Foundation Trust holds the information collected directly from the participant and sends the information to NHS Digital. The NHS Digital data is then sent to The Royal Devon University Healthcare NHS Foundation Trust. The objective of this study will be to extract DNA from blood samples obtained from all consenting diabetic and control participants. Clinical information will also be gathered about a participant’s health and wellbeing, family history and diabetes treatment. With specific consent from study participants, information will be extracted about their diabetes and related conditions from health records for the duration of the study in order to follow up on participants health status. The DARE Study closed to recruitment on 31 July 2017 and is now in follow up until the proposed end date of 31 July 2047.

A primary aim of the DARE Study is to investigate and understand diabetes and how it progresses and leads to complications. The increased cardiovascular death rate seen in patients with diabetes is a major problem that needs further study. A key outcome of the DARE Study will relate to mortality in diabetes, as previous studies have been unable to report time and cause of death. The 30 years follow up duration for the study has been based on average life expectancy figures, given that the median age of diabetes study participants at time of recruitment was 68 years (60, 75). The mean Age for this cohort is 65.9.

It will be important to continue to process and share identifiable information about participants with NHS Digital for the entire duration of the follow up period to enable the Royal Devon University Healthcare NHS Foundation Trust to access mortality data (Date, Time and Cause of Death) about the DARE Study cohort. Identifiable information about participants is held by the DARE Study team at the NIHR Exeter Clinical Research Facility (Exeter CRF) which is a partnership between The University of Exeter Medical School, College of Medicine and Health and the Royal Devon University Healthcare NHS Foundation Trust.

The data under this Agreement will only be accessed by researchers substantively employed by the Royal Devon University Healthcare NHS Foundation Trust.

The DARE Study obtained specific consent from participants to join a database and to be contacted about future research studies. The database is a way to recruit the most appropriate participants for future diabetes studies. To ensure that personal information about participants is up to date and accurate, the DARE Study needs to ensure this dataset is complete and populated with the latest identifiers (name, current address) plus information on whether a participant has left the NHS.

It is also a priority to have a large collection of patients with Type 2 diabetes and associate controls from a defined geographical region to enable future research work into how genetic susceptibility and environmental factors contribute to Diabetes and the development of complications to progress.

The study has arisen from discussions at meetings held with patients with diabetes (through patients' organisation Diabetes UK), who felt that further research into who developed diabetes and who developed diabetes complications was important. A patient is on the steering committee and The DARE Study steering committee included a patient representative (who read and ave suggestions on the protocol and patient information sheet), a GP representative, the CI, study PIs, study Research Nurses and a statistician. Their collective role is to monitor progress of the study. The decision to collect and process data from NHS Digital under this Agreement was made by the study CI who is a substantive employee of Royal Devon University Healthcare NHS Foundation Trust. Therefore the Royal Devon University Healthcare NHS Foundation Trust are deemed to be the sole data controller.

Royal Devon University Healthcare NHS Foundation Trust is the sponsor for the DARE Research Study and is the Data Controller with responsibility for determining the purpose and manner in which any personal data collected, or are processed for this study.

From NHS Digital, the cohort data is sent to the Royal Devon University Healthcare NHS Foundation Trust who processes personally-identifiable data from participants who have consented to take part in the DARE Study in order to conduct research and improve health, care and services for patients with Diabetes.

The study is funded by the National Institute for Health & Care Research (NIHR) and therefore the processing of personally-identifiable information is lawful under GDPR Article 6(1)(e); as processing is ‘necessary for the performance of a task carried out in the public interest’. Where the DARE Study processes special categories data, for example data concerning participant’s health, racial or ethnic origin, processing is lawful under GDPR Article 9(2)(j); as processing is necessary for ‘scientific or historical research purposes’.

Royal Devon University Healthcare NHS Foundation Trust is the data processor for the DARE Study and is also the sponsor. It is the Royal Devon University Healthcare NHS Foundation Trust who determines what data is collected (both indirectly from the care organisation and directly from the participant) for the research study and the purpose for which data is collected.

The Royal Devon University Healthcare NHS Foundation Trust will also process the data under this Agreement processing with responsibility for the management and oversight of the study cohort database.

The Exeter Clinical Research Facility is a purpose built facility within the Royal Devon and Exeter Hospital, which was set up to encourage collaborations between research staff from the University of Exeter and the Royal Devon University Healthcare NHS Foundation Trust. Researchers from the University of Exeter will not access the data under this Agreement. The processing of research data in such a way that the data can no longer be attributed to a study participant, will only be carried out by members of the DARE study team who are substantively employed by the Royal Devon University Healthcare NHS Foundation Trust. The study database is password-protected and is held on a secure NHS server.

A primary aim of the DARE Study is to investigate and understand diabetes and how it progresses and leads to complications. A key outcome of the DARE Study will relate to mortality. It is therefore very important that the DARE Study receives Date of Inquest and Place of Death data for this purpose. It is also crucial to receive information about the participants latest occupation, as this could have an impact on the participants health and could be correlated to progression of diabetes and the development of complications. Researchers require latest identifiers including surname (also known as Surname of Deceased) Third Forename of Deceased, in order to ensure that participants are correctly matched on the study database.

The DARE Study has sought specific consent from participants to join a database and to be contacted about future research studies. In order to contact/recruit the most appropriate participants for future diabetes studies including those studies who may wish to base their study eligibility on gender, it is essential to ensure that personal information held about participants is up to date and accurate. Therefore, latest gender would be essential for this purpose.

The DARE Study is now in follow up until the proposed end date on 31 July 2047. A final study report will be published in 2047. The study team are aiming to analyse mortality data to look at predictors of mortality in the diabetes cohort compared to the control group. Mortality data from greater numbers of patients is required to achieve a sufficiently robust dataset for this question. As part of the DARE study follow up process, Royal Devon University Healthcare NHS Foundation Trust will continue to collect mortality data from NHS Digital to achieve the required dataset for this analysis.

Health and care research will serve the public interest and the interests of society as a whole; the DARE Study does this by following the UK Policy Framework for Health and Social Care Research.

The Royal Devon University Healthcare NHS Foundation Trust have already submitted several results/papers arising from this work to internationally recognised journals such as the New England Journal of Medicine, The Lancet and Nature Genetics and/or the top diabetes-specific journals such as Diabetes care, Diabetologia and Diabetic Medicine. Further results that arise from this study will be submitted to both national and international conferences for both poster and oral sessions and disseminated at local trust and University of Exeter organised research events.

The results will also be disseminated to patients with diabetes by using local publications such as at Diabetes UK group meetings and national Diabetes UK publications and meetings.

Participants taking part in the DARE Study will also be informed about study results via the website www.diabetesgenes.org/current-research/dare/ and study newsletters.

The study team have, and will continue to actively liaise with the Royal Devon University Healthcare NHS Foundation Trust Communications Office and University of Exeter Press and Media Office for assistance with effective dissemination of important results via social media and press releases.

These active communication and dissemination activities will ensure that any results arising from this study reaches the target audience.

At this present time the DARE Study has no intention of developing prediction models for mortality in diabetes. If in the future this was decided then specific funding would be sourced for this purpose.

For a previous clinical prediction model (MODY calculator - to determine the likelihood of MODY in patients with young-onset diabetes) which was developed by the Diabetes Research Team in Exeter and published in 2012, is completely free and open access. The model equations were published and freely available for anyone who wants to validate/use the models in their own cohorts.

Outputs delivered using the data under this Agreement so far include:

A study led by Dr Christopher Clark an Academic Clinician at the University of Exeter used mortality data provided by NHS Digital to investigate whether differences in blood pressure between arms are associated with vascular disease and increased mortality; as this had not been reported in diabetes. His research was published in Diabetes Care journal.

Clark C E, Steele A M, Taylor R S, Shore A C, Ukoumunne O C, Campbell J C. Interarm Blood Pressure Difference in People With Diabetes: Measurement and Vascular and Mortality Implications. Diabetes Care 2014 Jun; 37(6): 1613-1620

There have already been some papers arising from the DARE study published in: - Diabetic Medicine, the official journal of Diabetes UK; The Review of Diabetic Studies; Diabetes Care; Nursing Times.

Diabetic Medicine: -

A small study with big ambitions: 10 year review examining the impact and achievements of the Diabetes alliance for Research in England (DARE) within the Exeter NIHR Clinical Research Facility, Exeter and beyond.

The transcription factor 7-like 2 (TCF7L2) gene is associated with Type 2 diabetes in UK community-based cases, but the risk allele frequency is reduced compared with UK cases selected for genetic studies.

Difference in phenotype of patients recruited for genetic studies on an epidemiological rather than a familial based recruitment criteria.

Angiotensin-converting enzyme gene insertion/deletion polymorphism is not associated with severe hypoglycaemia in patients with type 2 diabetes.

What is the best case collection for defining the role of Type 2 diabetes genes? A comparison of the Diabetes UK Warren 2 Cases (W2C) and The Exeter Research Alliance for Diabetes (EXTRA).

The Review of Diabetic Studies: - The Impact of Angiotensin-converting enzyme insertion/deletion polymorphism on severe hypoglycaemia in Type 2 diabetes.

Nursing Times: - Implementing a research project on the development of diabetes.

Outputs from the DARE Study have already made a valuable contribution to clinical care for Diabetes patients at the Royal Devon and Exeter NHS Foundation Trust. Researchers have found that the use of a simple urine test, urinary C-peptide: creatinine ratio (UCPCR) offers a practical non-invasive alternative to a C-peptide blood test. A C-peptide test is used to measure if patients with diabetes are making their own insulin. It is often used to find out whether someone has Type 1 or Type 2 diabetes. However, this blood test has been shown to be less reliable in patients whose kidneys are not working properly. The UCPCR test was developed using clinical data and samples donated from DARE participants and the test better reflects the amount of insulin being produced than repeated C-peptide measurements in patients with diabetes and kidney damage.

Researchers used mortality data provided by NHS Digital to investigate whether differences in blood pressure between arms are associated with vascular disease and increased mortality; as this had not been reported in diabetes.

As of May 2022, the DARE Study is open and in follow up. The Royal Devon University Healthcare NHS Foundation Trust plan to continue to collect mortality data (Date, Time and Cause of Death) on the DARE cohort until the proposed study end date 31 July 2047.

Both major types of diabetes (Type 1 and Type 2) represent classical “complex disorders” with both genetic and environmental factors playing an important role. There is considerable evidence that genetic factors are important in the development of diabetes. Evidence for this includes the clustering of disease in families, a high concordance rate in identical twins and migration studies. However, the majority of Type 2 forms of diabetes are greatly influenced by environment as shown by the rapidly increasing prevalence in the last two decades. This does not represent an alteration in the population gene frequency but rather changes in the environment, specifically a reduction in physical activity and increased food consumption.

Diabetes is a major cause of morbidity and mortality and has been estimated to account for 10% of NHS spending and this is likely to increase. Therefore, understanding how the disease develops, progresses over time and how to prevent complications is a major health priority. The Diabetes Alliance for Research in England (DARE) study, is an observational, prospective cohort study. The study was set up in 2007 to establish an epidemiologically based sample of patients with diabetes (Diabetes group) and those without (Control group), within the Exeter region. Participants are recruited in the Exeter region and the data requested relates to these participants rather than the full nationwide cohort. The objective of this study will be to extract DNA from blood samples obtained from all consenting diabetic and control participants. Clinical information will also be gathered about a participant’s health and wellbeing, family history and diabetes treatment. With specific consent from study participants, information will be extracted about their diabetes and related conditions from health records for the duration of the study in order to follow up on participants health status. The DARE Study closed to recruitment on 31 July 2017 and is now in follow up until the proposed end date on 31 July 2047.

A primary aim of the DARE Study is to investigate and understand diabetes and how it progresses and leads to complications. The increased cardiovascular death rate seen in patients with diabetes is a major problem that needs further study. A key outcome of the DARE Study will relate to mortality in diabetes, as previous studies have been unable to report time and cause of death. The 30 years follow up duration for the study has been based on average life expectancy figures, given that the median age of diabetes study participants at time of recruitment was 68 years (60, 75). The mean Age for this cohort is 65.9.

It will be important to continue to process and share identifiable information about participants with NHS Digital for the entire duration of the follow up period to enable the Royal Devon & Exeter Foundation Trust to access mortality data (Date, Time and Cause of Death) about the DARE Study cohort.

The DARE Study will also seek specific consent from participants to join a database and to be contacted about future research studies. The database will be used as a way to recruit the most appropriate participants for future diabetes studies. To ensure that personal information about participants is up to date and accurate, the DARE Study needs to ensure this dataset is complete and populated with the latest identifiers (name, current address, whether a participant has left the NHS).

It is also a priority to have a large collection of patients with Type 2 diabetes and associate controls from a defined geographical region to enable future research work into how genetic susceptibility and environmental factors contribute to Diabetes and the development of complications to progress.

The study has arisen from discussion at meetings held with patients with diabetes (through patients organisation Diabetes UK) who felt that further research into who developed diabetes and who developed diabetes complications is important. A patient is on the steering committee and has read and given suggestions on the protocol and patient information sheet.

The Royal Devon and Exeter NHS Foundation Trust is the sponsor for the DARE Research Study based in the United Kingdom and is the registered Data Controller responsible for determining the purpose and manner in which any personal data collected for clinical research are, or are to be processed for this study.

The Royal Devon and Exeter NHS Foundation Trust will use and process personally-identifiable information from people who have consented to take part in the DARE Study in order to conduct research and improve health, care and services for patients with Diabetes.

The Royal Devon and Exeter NHS Foundation Trust is a publicly-funded organisation and therefore the processing of personally-identifiable information is lawful under GDPR Article 6(1) (e); as processing is ‘necessary for the performance of a task carried out in the public interest’. Where the DARE Study processes special categories data, for example data concerning participant’s health, racial or ethnic origin, processing is lawful under GDPR Article 9 (2) (j); as processing is necessary for ‘scientific or historical research purposes’.

Health and care research will serve the public interest and the interests of society as a whole; the DARE Study does this by following the UK Policy Framework for Health and Social Care Research. As the participants have consented to partake in the study, the Royal Devon and Exeter NHS Foundation Trust do not forsee any moral or ethical issues arising from the dissemination of this data.

Royal Devon and Exeter NHS Foundation Trust aim to submit the results/papers arising from this work to internationally recognised journals such as the New England Journal of Medicine, The Lancet and Nature Genetics and/or the top diabetes-specific journals such as Diabetes care, Diabetologia and Diabetic Medicine. Results that arise from this study will be submitted to both national and international conferences for both poster and oral sessions and disseminated at local trust and University of Exeter organised research events.

The results will also be disseminated to patients with diabetes by using local publications such as DIRECT (a SW Peninsula-wide Diabetes Charity), at Diabetes UK group meetings and national Diabetes UK publications and meetings.

Participants taking part in the DARE Study will also be informed about study results via the website www.diabetesgenes.org/current-research/dare/ and study newsletters.

The study team will actively liaise with the Royal Devon and Exeter NHS Foundation Trust Communications Office and University of Exeter Press and Media Office for assistance with effective dissemination of important results via social media and press releases.

The DARE Study is now in follow up until the proposed end date on 31 July 2047. A final study report will be published in 2047. The study team are aiming to analyse mortality data to look at predictors of mortality in the diabetes cohort compared to the control group. Mortality data from greater numbers of patients is required to achieve a sufficiently robust dataset for this question. As part of the DARE study follow up process, Royal Devon and Exeter NHS Foundation Trust will continue to collect mortality data from NHS Digital to achieve the required dataset for this analysis.

These active communication and dissemination activities will ensure that any results arising from this study reaches the target audience.

At this present time the DARE Study has no intention of developing prediction models for mortality in diabetes. If in the future this was decided then specific funding would be sourced for this purpose.

For a previous clinical prediction model (MODY calculator - to determine the likelihood of MODY in patients with young-onset diabetes) which was developed by the Diabetes Research Team in Exeter and published in 2012, is completely free and open access. The model equations were published and freely available for anyone who wants to validate/use the models in their own cohorts.

Since the last application in March 2018, no further papers have been written but it is envisaged that there will be some in the future. Currently, the major benefit is ensuring that the Royal Devon and Exeter NHS Foundation Trust does not try and contact those participants who have passed away and to minimise any distress to participants' families.

Outputs from the DARE Study have already made a valuable contribution to clinical care for Diabetes patients at the Royal Devon and Exeter NHS Foundation Trust. A Principal Clinical Scientist at the Royal Devon and Exeter Hospital and his colleagues from the University of Exeter have discovered that the use of a simple urine test, urinary C-peptide: creatinine ratio (UCPCR) offers a practical non-invasive alternative to a C-peptide blood test. A C-peptide test is used to measure if patients with diabetes are making their own insulin. It is often used to find out whether someone has Type 1 or Type 2 diabetes. However, this blood test has been shown to be less reliable in patients whose kidneys are not working properly. The UCPCR test was developed using clinical data and samples donated from DARE participants and the test better reflects the amount of insulin being produced than repeated C-peptide measurements in patients with diabetes and kidney damage.

A study led by Dr Christopher Clark an Academic Clinician at the University of Exeter used mortality data provided by NHS Digital to investigate whether differences in blood pressure between arms are associated with vascular disease and increased mortality; as this had not been reported in diabetes. His research was published in Diabetes Care journal.

Clark C E, Steele A M, Taylor R S, Shore A C, Ukoumunne O C, Campbell J C. Interarm Blood Pressure Difference in People With Diabetes: Measurement and Vascular and Mortality Implications. Diabetes Care 2014 Jun; 37(6): 1613-1620

There have already been some papers arising from the DARE study published in: - Diabetic Medicine, the official journal of Diabetes UK; The Review of Diabetic Studies; Diabetes Care; Nursing Times.

Diabetic Medicine: -

A small study with big ambitions: 10 year review examining the impact and achievements of the Diabetes alliance for Research in England (DARE) within the Exeter NIHR Clinical Research Facility, Exeter and beyond.

The transcription factor 7-like 2 (TCF7L2) gene is associated with Type 2 diabetes in UK community-based cases, but the risk allele frequency is reduced compared with UK cases selected for genetic studies.

Difference in phenotype of patients recruited for genetic studies on an epidemiological rather than a familial based recruitment criteria.

Angiotensin-converting enzyme gene insertion/deletion polymorphism is not associated with severe hypoglycaemia in patients with type 2 diabetes.

What is the best case collection for defining the role of Type 2 diabetes genes? A comparison of the Diabetes UK Warren 2 Cases (W2C) and The Exeter Research Alliance for Diabetes (EXTRA).

The Review of Diabetic Studies: - The Impact of Angiotensin-converting enzyme insertion/deletion polymorphism on severe hypoglycaemia in Type 2 diabetes.

Nursing Times: - Implementing a research project on the development of diabetes.

Both major types of diabetes (Type 1 and Type 2) represent classical “complex disorders” with both genetic and environmental factors playing an important role. There is considerable evidence that genetic factors are important in the development of diabetes. Evidence for this includes the clustering of disease in families, a high concordance rate in identical twins and migration studies. However, the majority of Type 2 forms of diabetes are greatly influenced by environment as shown by the rapidly increasing prevalence in the last two decades. This does not represent an alteration in the population gene frequency but rather changes in the environment, specifically a reduction in physical activity and increased food consumption.

Diabetes is a major cause of morbidity and mortality and has been estimated to account for 10% of NHS spending and this is likely to increase. Therefore, understanding how the disease develops, progresses over time and how to prevent complications is a major health priority. The Diabetes Alliance for Research in England (DARE) study, is an observational, prospective cohort study. The study was set up in 2007 to establish an epidemiologically based sample of patients with diabetes (Diabetes group) and those without (Control group), within the Exeter region. Participants are recruited in the Exeter region and the data requested relates to these participants rather than the full nationwide cohort. The objective of this study will be to extract DNA from blood samples obtained from all consenting diabetic and control participants. Clinical information will also be gathered about a participant’s health and wellbeing, family history and diabetes treatment. With specific consent from study participants, information will be extracted about their diabetes and related conditions from health records for the duration of the study in order to follow up on participants health status. The DARE Study closed to recruitment on 31 July 2017 and is now in follow up until the proposed end date on 31 July 2047.

A primary aim of the DARE Study is to investigate and understand diabetes and how it progresses and leads to complications. The increased cardiovascular death rate seen in patients with diabetes is a major problem that needs further study. A key outcome of the DARE Study will relate to mortality in diabetes, as previous studies have been unable to report time and cause of death. The 30 years follow up duration for the study has been based on average life expectancy figures, given that the median age of diabetes study participants at time of recruitment was 68 years (60, 75). The mean Age for this cohort is 65.9.

It will be important to continue to process and share identifiable information about participants with NHS Digital for the entire duration of the follow up period to enable the Royal Devon & Exeter Foundation Trust to access mortality data (Date, Time and Cause of Death) about the DARE Study cohort.

The DARE Study will also seek specific consent from participants to join a database and to be contacted about future research studies. The database will be used as a way to recruit the most appropriate participants for future diabetes studies. To ensure that personal information about participants is up to date and accurate, the DARE Study needs to ensure this dataset is complete and populated with the latest identifiers (name, current address, whether a participant has left the NHS).

It is also a priority to have a large collection of patients with Type 2 diabetes and associate controls from a defined geographical region to enable future research work into how genetic susceptibility and environmental factors contribute to Diabetes and the development of complications to progress.

The study has arisen from discussion at meetings held with patients with diabetes (through patients organisation Diabetes UK) who felt that further research into who developed diabetes and who developed diabetes complications is important. A patient is on the steering committee and has read and given suggestions on the protocol and patient information sheet.

The Royal Devon and Exeter NHS Foundation Trust is the sponsor for the DARE Research Study based in the United Kingdom and is the registered Data Controller responsible for determining the purpose and manner in which any personal data collected for clinical research are, or are to be processed for this study.

The Royal Devon and Exeter NHS Foundation Trust will use and process personally-identifiable information from people who have consented to take part in the DARE Study in order to conduct research and improve health, care and services for patients with Diabetes.

The Royal Devon and Exeter NHS Foundation Trust is a publicly-funded organisation and therefore the processing of personally-identifiable information is lawful under GDPR Article 6(1) (e); as processing is ‘necessary for the performance of a task carried out in the public interest’. Where the DARE Study processes special categories data, for example data concerning participant’s health, racial or ethnic origin, processing is lawful under GDPR Article 9 (2) (j); as processing is necessary for ‘scientific or historical research purposes’.

Health and care research will serve the public interest and the interests of society as a whole; the DARE Study does this by following the UK Policy Framework for Health and Social Care Research. As the participants have consented to partake in the study, the Royal Devon and Exeter NHS Foundation Trust do not forsee any moral or ethical issues arising from the dissemination of this data.

Royal Devon and Exeter NHS Foundation Trust aim to submit the results/papers arising from this work to internationally recognised journals such as the New England Journal of Medicine, The Lancet and Nature Genetics and/or the top diabetes-specific journals such as Diabetes care, Diabetologia and Diabetic Medicine. Results that arise from this study will be submitted to both national and international conferences for both poster and oral sessions and disseminated at local trust and University of Exeter organised research events.

The results will also be disseminated to patients with diabetes by using local publications such as DIRECT (a SW Peninsula-wide Diabetes Charity), at Diabetes UK group meetings and national Diabetes UK publications and meetings.

Participants taking part in the DARE Study will also be informed about study results via the website www.diabetesgenes.org/current-research/dare/ and study newsletters.

The study team will actively liaise with the Royal Devon and Exeter NHS Foundation Trust Communications Office and University of Exeter Press and Media Office for assistance with effective dissemination of important results via social media and press releases.

The DARE Study is now in follow up until the proposed end date on 31 July 2047. A final study report will be published in 2047. The study team are aiming to analyse mortality data to look at predictors of mortality in the diabetes cohort compared to the control group. Mortality data from greater numbers of patients is required to achieve a sufficiently robust dataset for this question. As part of the DARE study follow up process, Royal Devon and Exeter NHS Foundation Trust will continue to collect mortality data from NHS Digital to achieve the required dataset for this analysis.

These active communication and dissemination activities will ensure that any results arising from this study reaches the target audience.

At this present time the DARE Study has no intention of developing prediction models for mortality in diabetes. If in the future this was decided then specific funding would be sourced for this purpose.

For a previous clinical prediction model (MODY calculator - to determine the likelihood of MODY in patients with young-onset diabetes) which was developed by the Diabetes Research Team in Exeter and published in 2012, is completely free and open access. The model equations were published and freely available for anyone who wants to validate/use the models in their own cohorts.

Since the last application in March 2018, no further papers have been written but it is envisaged that there will be some in the future. Currently, the major benefit is ensuring that the Royal Devon and Exeter NHS Foundation Trust does not try and contact those participants who have passed away and to minimise any distress to participants' families.

Outputs from the DARE Study have already made a valuable contribution to clinical care for Diabetes patients at the Royal Devon and Exeter NHS Foundation Trust. A Principal Clinical Scientist at the Royal Devon and Exeter Hospital and his colleagues from the University of Exeter have discovered that the use of a simple urine test, urinary C-peptide: creatinine ratio (UCPCR) offers a practical non-invasive alternative to a C-peptide blood test. A C-peptide test is used to measure if patients with diabetes are making their own insulin. It is often used to find out whether someone has Type 1 or Type 2 diabetes. However, this blood test has been shown to be less reliable in patients whose kidneys are not working properly. The UCPCR test was developed using clinical data and samples donated from DARE participants and the test better reflects the amount of insulin being produced than repeated C-peptide measurements in patients with diabetes and kidney damage.

A study led by Dr Christopher Clark an Academic Clinician at the University of Exeter used mortality data provided by NHS Digital to investigate whether differences in blood pressure between arms are associated with vascular disease and increased mortality; as this had not been reported in diabetes. His research was published in Diabetes Care journal.

Clark C E, Steele A M, Taylor R S, Shore A C, Ukoumunne O C, Campbell J C. Interarm Blood Pressure Difference in People With Diabetes: Measurement and Vascular and Mortality Implications. Diabetes Care 2014 Jun; 37(6): 1613-1620

There have already been some papers arising from the DARE study published in: - Diabetic Medicine, the official journal of Diabetes UK; The Review of Diabetic Studies; Diabetes Care; Nursing Times.

Diabetic Medicine: -

A small study with big ambitions: 10 year review examining the impact and achievements of the Diabetes alliance for Research in England (DARE) within the Exeter NIHR Clinical Research Facility, Exeter and beyond.

The transcription factor 7-like 2 (TCF7L2) gene is associated with Type 2 diabetes in UK community-based cases, but the risk allele frequency is reduced compared with UK cases selected for genetic studies.

Difference in phenotype of patients recruited for genetic studies on an epidemiological rather than a familial based recruitment criteria.

Angiotensin-converting enzyme gene insertion/deletion polymorphism is not associated with severe hypoglycaemia in patients with type 2 diabetes.

What is the best case collection for defining the role of Type 2 diabetes genes? A comparison of the Diabetes UK Warren 2 Cases (W2C) and The Exeter Research Alliance for Diabetes (EXTRA).

The Review of Diabetic Studies: - The Impact of Angiotensin-converting enzyme insertion/deletion polymorphism on severe hypoglycaemia in Type 2 diabetes.

Nursing Times: - Implementing a research project on the development of diabetes.