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Reversal of Hypoglycemia Unawareness in a Long-Term Type 1 Diabetic Patient by Improvement of ß-Adrenergic Sensitivity after Prevention of Hypoglycemia

Department IV of Internal Medicine, Endocrinology, and Pathobiochemistry, University of Tubingen, 72076 Tubingen, Germany; and the Departments of Medicine, Physiology, and Pharmacology, University of Rochester School of Medicine, Rochester, New York 14642

Address all correspondence and requests for reprints to: Dr. Andreas Fritsche, Medizinische Universitätsklinik IV, Otfried Müller Strasse 10, 72076 Tubingen, Germany. E-mail: andreas.fritsche{at}med.unituebingen.de

The purpose of this study was to assess the effect of strict avoidance of hypoglycemia on ß-adrenergic sensitivity in a type 1 diabetic patient with hypoglycemia unawareness and a diabetes duration of 55 yr. ß-Adrenergic sensitivity was determined by an isoproterenol test and was expressed as the lowest dose of isoproterenol that increases the heart rate by 25 beats/min (IC₂₅). Plasma epinephrine and symptom responses to hypoglycemia were determined during a 3-h hypoglycemic (3 mmol/L) clamp. Initially, the patient had a near-normal counterregulatory plasma epinephrine response to hypoglycemia but reduced ß-adrenergic sensitivity (IC₂₅, 2 µg) compared to 10 hypoglycemia aware, type 1 diabetic patients (0.65 ± 0.14 µg) and 10 normal control subjects (1.13 ± 0.21 µg). After 1 yr of strict avoidance of blood glucose levels below 4 mmol/L, the IC₂₅ decreased to 0.25 µg, reflecting improved ß-adrenergic sensitivity. In conclusion, the reduced ß-adrenergic sensitivity in this patient was probably the reason for hypoglycemia unawareness and was reversed by strict avoidance of hypoglycemia.

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