Detecting hidden biomarkers to investigate and diagnose diabetic vascular pathology

Rationale

Diabetes is a common cause of heart disease, with patients in the UK with diabetes numbering 3.8 million in 2014. It is well known that diabetes severely damages blood vessels, causing heart attacks and strokes.

Identifying changes in blood vessels would allow earlier disease detection. Cells in blood vessels produce ‘biomarkers’ due to diabetes effects, which are later released into the circulation. This study will use our newly developed technique, in which we can collect proteins from cells without destroying them. The technique involves applying a chemical (SMA) which obtains proteins while leaving cells intact. This can assess if cells are changed by disease and track changes as disease develops. We will use this technology to find unreleased biomarkers, thus advancing the stage at which diabetes is detected. 

Work plan, study impacts

As the target is identifying ‘biomarkers’ of diabetes before the disease actually develops, we will use a model of disease where blood vessels are initially healthy but are certain to develop diabetes – a genetic model of diabetes in mice (as identifying ‘advance warning’ biomarkers in humans is unfeasible). We will simply breed and maintain an already-existing genetically modified mouse that models diabetes. We will collect blood vessel tissue from mice over a range of ages (up to 14 weeks) and sample from post-mortem tissue with SMA. We will also analyse blood and vessel wall changes, thereby correlating biomarker appearance with disease development. 

This study will identify specific markers of diabetes, identifying the disease earlier than currently possible. Detecting a ‘biomarker’ of change to blood vessels due to the pre-diabetes state will allow intervention to prevent diabetes before disease progress has gone too far to fully reverse. Our aim is for the ‘biomarkers’ found to provide clinical diagnosis tools, after further technique development. A broad gain is that earlier detection of imminent diabetes allows potentially huge savings in healthcare costs, as earlier treatment to prevent disease is far less expensive than management once developed. 

Animal welfare

This study is designed so that tissue samples are obtained without causing the animals any distress, pain or suffering. Other than the disease phenotype, there will be no other causes of distress or variation from normal laboratory animal maintenance and care. All staff handling animals, including the researcher dedicated to this project, will be fully trained in animal handling and care, including recognising signs of distress and the ability to quickly, humanely end suffering if necessary. 

Non-technical summary 

Read a non-technical summary of detecting hidden biomarkers to investigate and diagnose diabetic vascular pathology (PDF).

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