Severe hypoglycaemia remains the most feared acute side-effect of insulin treatment for type 1 diabetes. There is an evidence-based pathway (illustrated below) to help people reduce their risk of severe hypoglycaemia. It starts with structured education in insulin self-management and continues through use of improved glucose monitoring and insulin delivery systems - continuous glucose monitoring, insulin pump therapy (continuous subcutaneous insulin infusion) and hybrid closed loop systems in which the continuous glucose monitor informs the pump insulin delivery. However, not everyone gets full benefit from such interventions. Pumps, sensors and closed loop systems only protect against hypoglycaemia when they are being worn - they do not seem to improve peoples' own awareness of hypoglycaemia and ability to avoid episodes. And some people continue to experience severe hypoglycaemia despite access to the pathway or find themselves unable to use the technologies on offer. HARPdoc is a new approach as an adjunct to existing therapies to help people who are not achieving best protection from severe hypoglycaemia despite these.
HARPdoc was developed from research into the mechanisms of impaired awareness of hypoglycaemia. This research, conducted in many research units over many years, taught us that impaired awareness of hypoglycaemia – the major modifiable risk factor for severe hypoglycaemia – was caused and maintained by repeated exposure to hypoglycaemia. The conventional treatment pathways are thought to work by reducing people’s exposure to plasma glucose concentrations less than 3 mmol/l (54 mg/dl). People with treatment-resistant problematic hypoglycaemia describe beliefs and thoughts about their hypoglycaemia which can act as barriers to its avoidance. HARPdoc was developed specifically to address these thoughts and beliefs. It was piloted in 23 people in the UK with high rates of severe hypoglycaemia despite otherwise using insulin optimally and this has been followed by a randomised controlled trial, funded by the Juvenile Diabetes Research Foundation and run in the UK and in the US, in which HARPdoc not only reduced severe hypoglycaemia rates and improved hypoglycaemia awareness – it also improved mental health, reducing scores for diabetes distress, anxiety and depression.
An evidence-based pathway for minimising severe hypoglycaemia
The image below is based on the publication Choudhary et al, 2015. It shows a research example from each step of the pathway and its impact on severe hypoglycaemia rates, with blue bars showing pre-intervention rates and the orange bars post-intervention rates. HARPdoc should be able to help people who don’t get benefit from this pathway or who can’t engage with it.
DAFNE Hopkins D et al., Diabetes Care 2012: 35:1638–1642
HypoDE Heinemann et al., Lancet 2018; 391: 1367–77
SMILE Bosi E et al., Lancet Diabetes Endocrinol. 2019 ;7:462-472
UKITC Brooks G et al., Am J Transplant. 2013 Dec;13(12):3236-43