Restoration of hypoglycaemia awareness in patients with long-duration insulin-dependent diabetes

Lancet. 1994 Jul 30;344(8918):283-7. doi: 10.1016/s0140-6736(94)91336-6.


Hypoglycaemia without warning is a dangerous complication of insulin-dependent diabetes mellitus and it limits the use of intensified insulin therapy to reduce chronic diabetic complications. To investigate the possibility of restoring awareness; symptomatic, cognitive, and hormonal responses to controlled hypoglycaemia were studied in insulin-dependent diabetic patients with long disease duration (6 with good glycaemic control and 6 with poor control) before and after hypoglycaemia avoidance. At the start of the study, all had loss of hypoglycaemia awareness. Responses to the initial challenge were small (pooled area under curve [AUC] adrenaline 5.75 [SE 0.07] nmol/L per 260 min, pooled AUC symptom score 80 [1.3]) and only started when plasma glucose was significantly lower than the 2.8 (0.1) mmol/L at which cognitive function deteriorated. After 4.1 (1.1) months' scrupulous hypoglycaemia avoidance, hormone and symptom responses to the challenge were increased (AUC adrenaline 15.9 [0.1] nmol/L per 260 min, p = 0.01; AUC symptom score 275 [7], p < 0.001), starting at plasma glucose concentrations significantly higher than that causing cognitive dysfunction. Glycosylated haemoglobin did not deteriorate significantly. We conclude that the normal hierarchy of subjective awareness before cognitive dysfunction during hypoglycaemia can be restored by avoiding hypoglycaemia. This is independent of disease duration or initial metabolic control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Awareness
  • Blood Glucose / metabolism
  • Cognition
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes Mellitus, Type 1 / psychology*
  • Epinephrine / blood
  • Glucagon / blood
  • Glucose Clamp Technique
  • Growth Hormone / blood
  • Humans
  • Hypoglycemia / physiopathology*
  • Hypoglycemia / prevention & control
  • Hypoglycemia / psychology*
  • Insulin / therapeutic use
  • Male
  • Middle Aged
  • Norepinephrine / blood


  • Blood Glucose
  • Insulin
  • Growth Hormone
  • Glucagon
  • Norepinephrine
  • Epinephrine