Counterregulatory deficiencies in diabetes

The importance of glucose as a fuel, particularly to meet the energy needs of the brain, which consumes approximately 25% of the energy supplied to the body, means that over millennia humans have developed a number of mechanisms that are designed to protect against low glucose. These mechanisms are collectively called the counterregulatory response and encompass a number of neural, endocrine and symptom responses that together act to restore normal glucose levels. In almost all individuals with type 1 diabetes, and longer duration type 2 diabetes, this counterregulatory defence response is compromised in a number of ways. This chapter will review the counterregulatory deficiencies in diabetes and discuss current thinking about how and why they develop. In particular, I will discuss why recurrent hypoglycaemia leads to further suppression of the counterregulatory response and will review the literature on altered glucose transport, alternate fuel metabolism, and the development of hypoglycaemia tolerance.