Glycemic control and neuropsychologic function during hypoglycemia in patients with insulin-dependent diabetes mellitus

Ann Intern Med. 1990 Jun 15;112(12):904-12. doi: 10.7326/0003-4819-112-12-904.


Study objective: To evaluate counterregulatory hormone secretion and neuropsychologic function during hypoglycemia in two groups of patients with insulin-dependent diabetes mellitus: those with good and those with poor glycemic control.

Design: Cross-sectional physiologic and neuropsychologic evaluation.

Setting: Clinical research unit of a referral-based diabetes clinic.

Patients: Eight patients with well controlled diabetes (glycosylated hemoglobin [HgbA1], 8.0% +/- 0.2%), nine patients with poorly controlled diabetes (HgbA1, 11.8% +/- 0.4%), and ten healthy persons.

Interventions: The insulin clamp technique was used to produce a stepwise decline in plasma glucose from 5.0 to 2.2 mmol/L over 3 hours. Tests of attention, memory, visual-spatial skills, visual-motor skills, and global cognition; a symptom survey; and counterregulatory hormone measurements were done at glucose decrements of 0.6 mmol/L.

Measurements and main results: Patients with well controlled diabetes did not differ statistically from those with poorly controlled diabetes regarding the median glucose threshold for dysfunction in visual-spatial skills, visual-motor skills, or global cognition. In contrast, glycemic thresholds for an increase in adrenergic symptoms and release of epinephrine, norepinephrine, cortisol, and growth hormone were lower in patients with well controlled diabetes than in those with poorly controlled diabetes (P less than 0.05 to 0.005).

Conclusions: Despite alterations in the glucose levels at which adrenergic symptoms of hypoglycemia occur and counterregulation begins, there is no statistically detectable change in the glucose threshold at which cognitive deterioration occurs in diabetic persons with strict glycemic control. This dissociation of neuropsychologic function and counterregulatory hormone secretion suggests that diabetic patients with good glycemic control are at increased risk for developing cognitive impairment before the onset of adrenergic symptoms during hypoglycemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analysis of Variance
  • Blood Glucose / physiology
  • Cognition Disorders / blood*
  • Cognition Disorders / chemically induced
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / psychology
  • Epinephrine / blood
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced
  • Hypoglycemia / psychology*
  • Insulin / adverse effects*
  • Male
  • Neuropsychological Tests
  • Psychomotor Performance / drug effects


  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Epinephrine