Understanding barriers to accurate early laboratory diagnosis and patient centric control of Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is a condition characterised by high blood glucose levels, with first onset during pregnancy. GDM increases the risk of complications for both mother and child. Evidently, early detection and treatment improve outcomes, but many women are at serious risk of going undiagnosed due to a lack of universally accepted diagnostic criteria, and disagreement over the glucose range deemed healthy. The most commonly used range is reported by the World Health Organisation to be 'somehow arbitrary'. Furthermore, poorly controlled GDM leads to adverse maternal and infant outcomes and increased likelihood of developing type 2 diabetes later in life. On the other hand, tight glucose control increases the risk of severe hypoglycaemia (low glucose levels), which may also compromise the wellbeing of mother and child.

The overall clinical goal is to improve the criteria, enable diagnosis as early as possible in pregnancy, discover better GDM markers and improve management of the condition to ensure that blood glucose levels remain under control throughout pregnancy. In addition to the impact on wellbeing and quality of life for both mother and child, any improvement in the management of this condition will reduce the burden on the national economy.

By facilitating hospital-based training for an engineering scientist, this discipline hop has the following aims:

- gaining for the principal investigator of a full grasp of the clinical challenges preventing the transformation of diagnosis and treatment of GDM;

- the establishment of a permanent network linking engineering science specialists with endocrinologists, obstetricians, pathologists, other allied healthcare colleagues and patients to tackle together the unsolved challenges of effective GDM care;

- the co-creation by the principal investigator and the other stakeholders above of a research strategy to improve GDM care.

The project will look at utilisation of routinely collected NHS data for research, give consideration to glucose variability to go beyond diagnosis based on glucose levels at single time points, and to personalisation for better management of glucose variability throughout pregnancy.

The training will include:

(a) engagement with patients and clinical professionals to understand how GDM is currently managed in the clinic, the practical realities constraining current practice, and how patients and different clinical professionals envisage improving care beyond today's approaches founded on population averages towards personalised alternatives

(b) training in available databases and laboratory sample testing to learn the structure of routinely collected NHS data, identify their limitations, and the implications for data analyses and modelling

(c) training in Good Clinical Practice covering ethical and regulatory requirements for research, the code of conduct for clinic-based research, a researcher's responsibilities towards study participants, limitations of measurements, reliability of data and other areas that are typically left unexplored by engineering and physical sciences researchers, and

(d) experience in recruitment for longitudinal measurements, together with assessment of our ability to recruit and the feasibility of personalisation based on longitudinal data obtained from continuous glucose monitoring, via preliminary data analysis and modelling.

As a long-term goal, the emergent collaboration aims to support the EPSRC Healthy Nation programme via better understanding of individual glucose variability, optimised care through effective diagnosis, patient-specific prediction and evidence-based treatment planning, minimisation of costs of care and reduction of risks to GDM patients and their children. The knowledge acquired from the project will form a platform to translate our findings into a large scale trial, which in turn can form the basis of changing current clinical practice in this field.

This proposed discipline hopping training and the subsequent research will bring benefits to the following areas and individuals.

People with gestational diabetes mellitus (GDM), healthcare professionals and wider society: GDM increases the risk of complications for both mother and child during pregnancy, at childbirth and beyond with increasing prevalence. It is estimated to affect 7% of all pregnancies. Evidence suggests that early detection and treatment improve pregnancy outcomes, whereas mis-diagnosis and a poorly controlled condition can lead to adverse maternal and infant outcomes, including pre-eclampsia, fetal macrosomia and respiratory distress syndrome, to name a few. They also increase the likelihood of developing type 2 diabetes later in life. Indeed, the incidence of type 2 diabetes among women with GDM is 20 to 50% within 5 years of giving birth. Currently, there are two main goals in the management of GDM: early diagnosis and prevention of complications through effective treatment. The existing diagnostic threshold is reported by the World Health Organisation to be 'somehow arbitrary', requiring further research to find ways of improving diagnosis and reduce the costs of treatment. People with GDM and the wider society will benefit from this line of research via improved accuracy and timing of diagnosis, effective personalised management and knowledge about self-management of GDM, ultimately easing the condition, preventing its complications, reducing negative impact on new born child, and reducing the numbers of type 2 diabetes cases due to GDM complications. This approach may also facilitate diagnostic interpretations in other areas of metabolic medicine, for example type 2 diabetes. Overall, this will improve quality of life, mitigate distress, reduce morbidity of patients with GDM, improve wellbeing of their friends and family and the wider community.

Economy: GDM is a growing public health concern and is associated with overall increased healthcare costs. The prevalence of GDM is increasing alongside the prevalence of diabetes mellitus, with the total costs for NHS diabetes care being over £1.5m an hour or 10% of the NHS budget for England and Wales. This equates to over £25,000 spent on diabetes every minute. In total, an estimated £14 billion is spent a year on treating diabetes and its complications. Figures for GDM are influenced by criteria used for diagnosis due to the fact that lower cut-off thresholds identify more women as having GDM, and by general obesity numbers and screening strategies. As is evident from research publications, modest improvements in glycaemic control and diagnostic strategy may generate a significant reduction in the cost of complications, at the same time as increasing the ability to participate productively within society, with significant savings to the UK economy. Improved GDM care also has great economic benefits through a reduced need for hospital admission due to hyper- and hypoglycaemia and costly procedures resulting from admission for GDM-related complications. There is also the potential for improved work productivity and contribution towards national GDP through avoidance of hypoglycaemia, which is essential for the quality of life and fitness to work of many individuals.

Knowledge: This cross-disciplinary initiative will form a critical pathway to economic and social impact through advances in the exploitation of biomedical engineering approaches in healthcare. Two fundamentally novel aspects relevant to healthcare are: (1) quantitative knowledge, developed for the first time, to understand the variety of glucose variations in women developing GDM; (2) a novel personalised approach to early diagnosis and management of GDM, aiming to establish a long-term programme for clinical use that is tailored to individual patients' phenotypes and needs.