Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation: no causal relation with diabetic autonomic neuropathy.

Abstract

Objective-To examine the traditional view that unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation in insulin dependent diabetes meilitus are manifestations of autonomic neuropathy.Design-Perspective assessment of unawareness of hypoglycaemia and detailed assessment of autonomic neuropathy in patients with insulin dependent diabetes according to the adequacy of their hypoglycaemic counterregulation.Setting-One routine diabetic unit in a university teaching hospital. IntroductionUnawareness of hypoglycaemia in diabetic patients is, by tradition, ascribed to autonomic neuropathy.'13 Some patients with insulin dependent diabetes mellitus have been shown to produce inadequate amounts of adrenaline and glucagon in response to hypoglycaemia, and these patients are more at risk from neuroglycopenia and hypoglycaemic coma.4 Diabetic autonomic neuropathy has also been suggested as the cause of defective adrenaline secretion in these patients,"7 and, in this way, as the cause of inadequate counterregulation. Previous studies investigating diabetic autonomic neuropathy and inadequate counterregulation have included only limited assessment of autonomic function, giving rise to conflicting results.89 We used an extensive battery of investigations of autonomic neuropathy to re-examine the relations among autonomic neuropathy, hypoglycaemic unawareness, and inadequate hypoglycaemic counterregulation.

Changes in Regional Brain 18F-Fluorodeoxyglucose Uptake at Hypoglycemia in Type 1 Diabetic Men Associated With Hypoglycemia Unawareness and Counter-Regulatory Failure

“…It is associated with a failure of the normal counterregulatory mechanisms that alert the diabetic patient to a falling blood glucose concentration (4). Most notably, the onset of the catecholamine and sympathetic responses to hypoglycemia is significantly delayed, with reduced magnitude of these responses at any given glucose level (5).…”

“…Hypoglycemia unawareness is associated with defects in the normal protective responses to a falling plasma glucose concentration (4). A greater degree of hypoglycemia is required to trigger hormonal and autonomic responses, and the magnitude of responses at any given glucose level is reduced (5).…”

Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects

“…of hypoglycaemia in these patients [3], thus leading into a vicious cycle [4]. Although glucose represents the main fuel for the brain, it is also possible that under conditions of glucose shortage, brain function is maintained by the uptake of other energetic substrates.…”

Human Insulin in Hypoglycemia: A New Arena?

“…No study has found defects in counterregulatory responses to the hypoglycemia of human insulin comparable DIABETES, VOL. 44, MARCH 1995 to those found in other hypoglycemia-unaware groups (17)(18)(19).…”