Hypo-RESOLVE

To treat diabetes, an increasing number of patients take insulin, which prevents them from experiencing blood glucose levels that are too high. But unfortunately, a common side-effect of taking insulin is that patients experience hypoglycaemic events, which happen when blood glucose levels drop.

On average people with type 1 diabetes will experience hypoglycaemic events 2-3 times per week, although some experience it on a daily basis. It can lead to cognitive decline, fainting episodes, cardiovascular events and even death. Everyone who has type 1 or type 2 diabetes and who has been treated with insulin will experience hypoglycaemia at one stage or another – but little is known about it. There is a known link between hypoglycaemia and cardiovascular events, but it is poorly understood.

Hypo-RESOLVE helped to narrow that gap in understanding, by investigating the mechanisms underlying the association of hypoglycaemia with cardiovascular disease, and also by examining the psychological impact of hypoglycaemia on diabetes patients and their families.

The project constructed a large clinical database consisting of data from almost 100 trials, and more than 80 000 people with type 1 or type 2 diabetes. Analysis of data from almost 40 000 people from this database showed that there was a clear association between hypoglycaemia in people living with diabetes of any type with cardiovascular events and mortality.

An experimental study was carried out by the project to test how people (those with and without diabetes) responded to hypoglycaemic events in real time. The participants were all exposed to one hour of hypoglycaemia and a range of clinical tests were run. Cognitive function declined in all participants, regardless of whether they had diabetes or not. A second result from this study was that hypoglycaemia caused a pro-inflammatory response in the bodies of the participants. This is important because inflammation of blood vessel walls can lead to a build-up of fat and cholesterol in the arteries which in turn increases the risk of cardiovascular morbidity and mortality.

One fascinating result from a large multi-country observational study was that people’s perception of a hypoglycaemic event had little to do with measured glucose values. Hypo-RESOLVE developed an app through which people with diabetes could track hypoglycaemia events in real-life and evaluate their impact on daily function. To test its efficacy, participants were asked to use the app while also wearing a sensor that detected their glucose level. The researchers saw that there was very little overlap in hypoglycaemic events detected by the sensor and hypoglycaemic events reported by the patient. Over 2/3 of the hypoglycaemic events detected by the sensor were not detected by the patient and 40% of the patient-reported hypoglycaemic events did not coincide with low glucose levels reported by the sensor. When hypoglycaemia was only detected by the sensor but not by the person, this had very little effect on their function, even if these events are ongoing.

This can cause problems on two fronts – one, that people with diabetes can’t tell when they are going into a low blood sugar episode and may suffer from severe consequences; and two, that patients who feel that their blood glucose is low when it is not may worry and under-treat, and this will have a long-term impact on their quality of life. People with type 1 diabetes in particular have been living with hypoglycaemia for their entire lives and they may be so used to the feeling of low blood gluicose that they can’t accurately detect when it is happening.

The Hypo-RESOLVE project conducted a study on how living with hypoglycaemic events affected the quality of life of not only the patients themselves but also their families and carers. A hypoglycaemic-specific patient reported outcome measure was developed that can be used in clinical research, in particular clinical trials, and an official Qualification Advice was obtained from the European Medicines Agency regarding this.