Does impaired awareness of hypoglycaemia develop through habituation

Funded PhD Project (European/UK Students Only)

Low blood sugar levels (hypo) are very common in people with Type 1 diabetes (T1D) who are reliant on insulin treatment to manage their illness. We know that once you have had one hypo the chance of having further episodes significantly. This can lead to the development of “Impaired Awareness of Hypoglycaemia” (IAH). 

In healthy people when blood sugar levels fall, the brain (and other organs such as the liver) sense these changes and send out signals to body to mobilise glucose stores, a process called the counterregulatory response (CRR). Unfortunately, in people with IAH, the body to become blind or “unaware” to falling glucose levels and the CRR is not activated until blood glucose levels fall dangerously low. This greatly increases the risk of severe hypo that can be fatal [8]. IAH affects almost 25% of people with T1D and worryingly the incidence of IAH has remained constant for the past 20-30 years [2]. 

Furthermore, there is currently there is no treatment for IAH other than avoiding hypo, very difficult if you are unaware of the fall in blood glucose. Our lab has recently proposed that IAH develops as a form of learned behaviour known as “Habituation”. 

This project will investigate the idea that impaired awareness of hypoglycaemia (IAH), results from cells in the brain learning/adapting to low blood glucose (hypo). This process is called habituation. The brain cells do this because a hypo is stressful, just like it is to people with diabetes and the body wants to reduce stressful experiences. We adapt to other stressful situations such as cold or exercise in a similar way. 

What is different in those with diabetes, however, is that this adaptation can lead to severe hypo that can be fatal. We have previously shown using an in vivo model of IAH that acute exposure to high-intensity exercise improves the ability to detect and respond to a subsequent hypo. These findings have recently been replicated in the clinic. Although very promising, these studies are based on only one of the ten features of habituation, and the others still need to be tested.

The project will expand upon this research using a well-established model of IAH In order to carry out this project, the student will become fully competent in all aspects of rodent surgery and clamping. This technique is the gold standard of testing the hypoglycaemic response and is well established in the McNeilly/McCrimmon lab. 

You will gain a Home Office Personal Licence and learn microsurgery and clamping from Dr McNeilly and members of the McCrimmon team. This project will run in parallel with on-going studies on the complications of hypoglycaemia. You will have the opportunity to attend meetings with a focus on hypoglycaemia and learn from experts in the field while working in a supportive and productive environment.