Towards a type 2 diabetes precision diagnosis approach with glycated haemoglobin (HbA1c) measurement (360G-Wellcome-227897_Z_23_Z)

Diabetes diagnosis is crucial to ensure appropriate treatment reduces the risks of life threatening complications associated with raised blood glucose. Since 2011, the measurement of glycated haemoglobin (HbA1c) has become the routine test used to diagnose type 2 diabetes (T2D) in the UK, and most of the world. HbA1c reflects glycaemia in the preceding 8 -12 weeks for any specific individual. However, our and others' work shows HbA1c is also altered between individuals by non-glycaemic factors such as genetic variants, ancestry and age. This means that the current use of a single diagnostic threshold for T2D will result in both over- and under-diagnosis, especially in UK minorities and older individuals, potentially increasing health disparities. Our goal is to better understand the non-glycaemic factors altering HbA1c so when it is used for T2D diagnosis it reflects a consistent level of glycaemia. We will identify genetic variants altering HbA1c in diverse populations; conduct participant physiological and longitudinal studies to assess T2D diagnosis and progression to complications; and develop diagnostic models leveraging additional clinical and genetic information, so that diagnosis reflects consistent underlying glycaemia. This will allow us to develop a precision diagnosis approach to define T2D diagnosis based on individualised HbA1c thresholds.