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Previous Volume 329:834-839 September 16, 1993 Number 12 Next

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ABSTRACT

Background A lack of appropriate autonomic warning symptoms before the development of neuroglycopenia occurs frequently in patients with diabetes mellitus. The pathogenesis of this phenomenon is unclear, but it is associated with intensive insulin therapy, prolonged duration of diabetes, frequent episodes of hypoglycemia, and impaired glucose counterregulation. Recently, it has been proposed that repeated episodes of hypoglycemia may themselves induce the phenomenon.

Methods To test this hypothesis and to determine whether the phenomenon is reversible, we assessed autonomic and neuroglycopenic symptoms, counterregulatory hormonal responses, and cognitive function during stepped hypoglycemic-clamp studies in 6 patients with insulinomas before and approximately six months after curative surgery and in 14 normal subjects matched for age, weight, and sex.

Results Before surgery, the patients with insulinomas had lower scores than the normal subjects for autonomic symptoms (mean [±SD], 3.5 ±0.8 vs. 9.6 ±4.5) and neuroglycopenic symptoms (2.8 ±1.5 vs. 8.9 ±5.3). The patients also had impaired counterregulatory hormonal responses (their plasma epinephrine, norepinephrine, glucagon, growth hormone, and cortisol responses before surgery were 187 ±227 pg per milliliter [1.03 ±1.25 nmol per liter], 223 ±85 pg per milliliter [1.32 ±0.50 nmol per liter], 86 ±21 ng per liter, 7.4 ±5.2 µg per liter, and 12.1 ±1.5 µg per deciliter [334 ±41 nmol per liter], respectively, as compared with 842 ±439 pg per milliliter [4.63 ±2.41 nmol per liter], 519 ±150 pg per milliliter [3.07 ±0.89 nmol per liter], 201 ±58 ng per liter, 25.3 ±13.7 µg per liter, and 26.3 ±1.2 µg per deciliter [726 ±33 nmol per liter] in the normal subjects) and less deterioration in cognitive function than the normal subjects during hypoglycemia (sum of z scores for seven tests of cognitive function, 1.7 ±1.9 vs. 8.9 ±3.5) (P<0.02 for all comparisons). Surgical cure reversed all these abnormalities (P not significant for all comparisons with the normal subjects).

Conclusions Hypoglycemia itself can induce unawareness of the autonomic and neuroglycopenic symptoms of hypoglycemia and decrease the counterregulatory hormonal responses to hypoglycemia.

Source Information

From the Second Department of Internal Medicine, Propaedeutic, Athens University, Athens, Greece (A.M., D.P., S.R.); the Istituto di Medicina Interna e Scienze Endocrine e Metaboliche, University of Perugia, Perugia, Italy (C.F., G.P., S.C., A.R., P.B., G.B.); the Whittier Institute for Diabetes and Endocrinology, La Jolla, Calif. (T.V., J.G.); and the Department of Medicine, Washington University School of Medicine, St. Louis (P.C.).

Address reprint requests to Dr. Gerich at the Whittier Institute for Diabetes and Endocrinology, 9894 Genesee Ave., La Jolla, CA 92037.

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