Avoidance of hypoglycemia restores hypoglycemia awareness by increasing beta-adrenergic sensitivity in type 1 diabetes

Ann Intern Med. 2001 May 1;134(9 Pt 1):729-36. doi: 10.7326/0003-4819-134-9_part_1-200105010-00009.

Abstract

Background: Lack of awareness of hypoglycemia is a major limiting factor in the management of type 1 diabetes.

Objective: To examine whether reduction in the number of episodes of hypoglycemia restores hypoglycemia awareness by influencing beta-adrenergic sensitivity in patients with type 1 diabetes.

Design: Controlled interventional study.

Setting: Research unit and outpatient diabetes clinic of a university hospital.

Patients: 10 men with type 1 diabetes and hypoglycemia unawareness (mean age [+/-SD], 46 +/- 16 years; mean duration of diabetes, 20 +/- 10 years).

Intervention: Strict avoidance of hypoglycemia.

Measurements: beta-Adrenergic sensitivity was measured by isoproterenol testing before and at 2 and 4 months after strict avoidance of hypoglycemia. Hypoglycemia awareness and catecholamine response were measured by performing hypoglycemic clamp (glucose level, 3 mmol/L [54 mg/dL]) before and after 4 months of avoidance of hypoglycemia.

Results: After 4 months, the mean (+/-SE) number of episodes of hypoglycemia (glucose level < 3.9 mmol/L [70 mg/dL]) decreased from 8.4 +/- 0.9 to 1.4 +/- 0.3 per week (P < 0.001). Hemoglobin A(1c) values increased from 0.068 +/- 0.003 (6.8% +/- 0.3%) to 0.077 +/- 0.003 (7.7% +/- 0.3%) (P < 0.001). Autonomic symptom scores during hypoglycemic clamp increased from 1.8 +/- 0.6 to 3.3 +/- 0.7 (P = 0.004) and did not significantly differ from those of normal participants (4.7 +/- 0.8) (P > 0.2). Although catecholamine responses to hypoglycemia were unchanged, the dose of isoproterenol necessary to increase heart rate by 25 beats/min (IC(25)) decreased from 1.96 +/- 0.43 microgram before treatment to 1.09 +/- 0.17 microgram after 4 months of treatment (P = 0.01), a value similar to that in normal participants (0.85 +/- 0.20 microgram) (P > 0.2). Improvements in beta-adrenergic sensitivity (change in IC(25)(-1)) were correlated with improvements in autonomic symptoms (r = 0.65; P = 0.04).

Conclusions: Avoidance of hypoglycemia in patients with type 1 diabetes who have hypoglycemia unawareness seems to restore hypoglycemia awareness, primarily by increasing beta-adrenergic sensitivity.

Publication types

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

MeSH terms

  • Adult
  • Analysis of Variance
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Epinephrine / blood
  • Glucose Clamp Technique
  • Glycated Hemoglobin A / metabolism
  • Heart Rate / drug effects
  • Humans
  • Hypoglycemia / etiology
  • Hypoglycemia / physiopathology*
  • Hypoglycemia / prevention & control*
  • Insulin / administration & dosage
  • Isoproterenol
  • Male
  • Middle Aged
  • Receptors, Adrenergic, beta / physiology*
  • Regression Analysis
  • Statistics, Nonparametric

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Receptors, Adrenergic, beta
  • Isoproterenol
  • Epinephrine