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

• Published in: Annals of internal medicine Vol. 134; no. 9 Pt 1; p. 729
• Main Authors: Fritsche, A, Stefan, N, Häring, H, Gerich, J, Stumvoll, M
• Format: Journal Article
• Language: English
• Published: United States 01.05.2001
• Subjects: 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
• ISSN: 0003-4819; 1539-3704
• DOI: 10.7326/0003-4819-134-9_Part_1-200105010-00009

Lack of awareness of hypoglycemia is a major limiting factor in the management of type 1 diabetes. 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. Controlled interventional study. Research unit and outpatient diabetes clinic of a university hospital. 10 men with type 1 diabetes and hypoglycemia unawareness (mean age [+/-SD], 46 +/- 16 years; mean duration of diabetes, 20 +/- 10 years). Strict avoidance of hypoglycemia. 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. 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). Avoidance of hypoglycemia in patients with type 1 diabetes who have hypoglycemia unawareness seems to restore hypoglycemia awareness, primarily by increasing beta-adrenergic sensitivity.