Endocrine Abstracts

Hypoglycaemia is the main factor limiting the use of intensive insulin regimens. The frequency is 0.1 – 0.3 episodes/person per day for symptomatic episodes and 1/year for severe ones. There is also an estimated mortality of 2–4% of people with type 1 diabetes mellitus (T1DM). Severe hypoglycaemia increases in frequency with duration of insulin treatment. The symptoms and signs of hypoglycaemia can be separated into those due to neuroglycopenia (cognitive impairment, seizures, coma) and neurogenic (adrenergic and cholinergic). The risk factors for development of hypoglycaemia relate to a relative or absolute excess of insulin e.g. exercise or missed meals. Recurrent hypoglycaemia is associated with the development of hypoglycaemia associated autonomic failure (HAAF). T1DM is also associated with the loss of glucagon secretion because the close interaction between the α and β cells is lost. Loss of glucagon coupled with HAAF which attenuates the catecholamine response to hypoglycaemia are the two major components to hypoglycaemia unawareness in T1DM. Recurrent hypoglycaemia leads to unawareness through HAAF. The mechanism of how HAAF develops ranges from altered neurotransmitter function, through perturbations in lactate metabolism to changes in cerebral neural networks. Selective serotonin-reuptake inhibitors increase the counter-regulatory response to hypoglycaemia. This would certainly reduce recurrent hypoglycaemic episodes. However, hypoglycaemia would still remain a risk as the loss of the glucagon response is independent of HAAF. Currently the best approaches to minimising hypoglycaemia are to better match insulin with carbohydrate and develop better exercise algorithms. In meta-analysis glucose sensing improves hypoglycaemia risk. The artificial and bionic pancreas projects will assist further in reducing hypoglycaemia risk while in the longer term cell based therapies are more likely to remove hypoglycaemia risk from the lives of patients with T1DM.