Hypoglycaemia in adult humans, with and without type 1 diabetes and impaired awareness

Abstract

Hypoglycaemia is a very common side-effect of insulin therapy for diabetes and directly affects cognitive function. It can be identified by the onset of symptoms and by blood glucose monitoring. Impaired awareness of hypoglycaemia is an acquired syndrome in people with insulin-treated diabetes. The definitions, frequency, causes, treatment and prevention of clinical hypoglycaemia and the effects on, and moderators of, cognitive function will be discussed. Two studies have examined the effects of hypoglycaemia on tests of particular cognitive domains in subjects with and without type 1 diabetes. Three further studies have examined the frequency of hypoglycaemia in people with and without impaired awareness, the prevalence of impaired awareness of hypoglycaemia (IAH) and have compared methods of assessing awareness of hypoglycaemia. In study 1 the effect of acute hypoglycaemia on psychomotor function was examined in healthy volunteers (n =20) and adults with type 1 diabetes (n=16). Although acute hypoglycaemia caused significant impairment of several psychomotor functions in nondiabetic adults, a lower magnitude of impairment was observed in those with type 1 diabetes. The potential mechanisms behind this are discussed. In study 2 the effect of acute hypoglycaemia on a simple two-choice reaction time test, which has a model with validated performance parameters, was examined in 14 nondiabetic volunteers. Application of the validated model to the results of this task revealed that hypoglycaemia affected central processing and was not related to the amount of evidence required to make a decision or to peripheral and motor processes. This study is the first to use this method to dissect the effects of hypoglycaemia on cognition and enhances understanding of the mechanism underlying neuroglycopenia in adults. In Study 3 the methods of evaluating awareness of hypoglycaemia were compared in people with type 1 diabetes. Good concordance in clinical characteristics and frequency of biochemical hypoglycaemia was observed between the methods described by Gold et al and Clarke et al but not with a Danish method. In study 4 continuous glucose monitoring (CGM) and home blood glucose monitoring were performed prospectively for 12 months in people with and without IAH. Those with IAH had a 1.6-fold higher incidence of biochemical hypoglycaemia as demonstrated by blood glucose monitoring, but CGM did not identify patients with IAH. In study 5 the prevalence of IAH in a large clinic population with type 1 diabetes was estimated and compared with earlier assessments. The overall prevalence was 20%.