Prediction and Detection of Hypoglycaemia in Type 1 Diabetes

Change log
Neupane, Sankalpa 

Patients with Type 1 Diabetes still suffer from recurrent and troublesome hypoglycaemia despite improvements in glucose monitoring, insulin delivery and structured education.
The key objectives of my thesis were to explore ways to identify patients at greater risk to develop hypoglycaemia and to investigate novel ways to prevent hypoglycaemic episodes by detecting this early and with ease. This might ultimately translate into reduction in overall risk of hypoglycaemia occurrence in those with Type 1 Diabetes. I investigated potential factors that could predict persistent presence of severe hypoglycaemia in the HypoCOMPaSS study, a multi-centre UK study examining clinical strategies to reduce burden of hypoglycaemia. Looking at a subset of these participants who underwent detailed hypoglycaemic clamp studies, I found no obvious parameters predicting persistent risk of severe hypoglycaemia. I then examined whether individual genetic factors might contribute to risk of persistent severe hypoglycaemia, exploring the association between polymorphisms in Angiotensin Converting Enzyme ACE gene and severe hypoglycaemia in 77 participants in HypoCOMPaSS study. Interestingly, I found that the homozygous DD ACE gene polymorphism was associated with a significantly increased risk of severe hypoglycaemia. Considering then practical approaches to trying to minimise hypoglycaemia risk, I examined the efficacy and safety of a novel implantable Continuous Glucose Monitoring Senseonics CGM System in 10 subjects with Type 1 Diabetes from the Cambridge cohort of the pivotal European PRECISE 1 study. In keeping with the global data, I found in Cambridge participants that this novel system was safe and its efficacy was comparable to commercially available Continuous Glucose Monitoring. This device was useful in detecting hypoglycaemia early with high device satisfaction among the users. I also explored alternative non-invasive methods to measure blood glucose and detect hypoglycaemia easily using breath sample in Type 1 Diabetes participants during experimental hypoglycaemia. The concentration of Isoprene exhaled in breath was significantly raised during hypoglycaemia. Finally, I looked at the stability of ‘diluted insulin aspart (NovoRapid®)’ in ambient temperature and CSII over 30 days. Both neat and diluted insulin aspart were stable beyond 30 days and could potentially be used by patients with T1D requiring very low insulin doses to avoid hypoglycaemia.

Evans, Dr Mark
hypoglycaemia, type 1 diabetes, detection
Doctor of Philosophy (PhD)
Awarding Institution
University of Cambridge
NIHR Cambridge Biomedical research centre, Diabetes UK, University of East Anglia Senseonics Inc. Dr Frank Waldron-Lynch