Insulin-induced hypoglycaemia in normal and diabetic man
This thesis begins with a consideration of the historical aspects of insulin-induced hypoglycaemia and then reviews the recent literature exploring the symptomatic, physiological and counter-regulatory hormonal responses to insulin-induced hypoglycaemia, the dependence of the brain on a continuous supply of glucose for normal functioning and the question of hypoglycaemia awareness. There then follows seven original chapters of investigation into differing aspects of insulin induced hypoglycaemia in normal and diabetic man. These include a retrospective assessment of the frequency and morbidity of hypoglycaemia in randomly selected insulin-treated patients, imaging studies (using single photon emission tomography) of regional cerebral blood flow in patients with a previous history of severe hypoglycaemia and in patients with hypoglycaemia unawareness. The patients previously affected by recurrent severe hypoglycaemia show an increased isotope uptake in the frontal cortex and those with hypoglycaemia unawareness also have increased frontal blood flow with a further augmentation in response to acute hypoglycaemia. The area of possible hypoglycaemia induced cognitive deficiency is considered and chapter 5 compares the frequency of hypoglycaemia and the cognitive performance of patients with a history of hypoglycaemia unawareness. There is a significantly greater frequency of severe hypoglycaemia in the unaware patients but no evidence of statistically significant cognitive impairment. In studies 7 and 8 the effect of human insulin on awareness of hypoglycaemia is considered in both the clinical and laboratory setting and no evidence to support the hypothesis of a reduction in hypoglycaemia awareness secondary to human insulin is found. In chapter 9 the question of the effect of an acute episode of hypoglycaemia to reduce the responses to subsequent hypoglycaemia is discussed.