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Abstract
Previous studies have shown that hypoglycemia may reduce counterregulatory responses
to subsequent hypoglycemia in healthy subjects and in patients with diabetes. The
effect of hypoglycemia on the hormonal response to a nonhypoglycemic stimulus is uncertain.
To test the hypothesis that the cortisol response to corticotropin (ACTH) infusion
is independent of antecedent hypoglycemia, 10 healthy subjects received a standard
ACTH infusion (0.25 mg Cosyntropin [Organon, West Orange, NJ] intravenously over 240
minutes) at 8:00 am on day 1 and day 3 and a hypoglycemic insulin clamp study (1 mU/kg/min) at 8:00 am on day 2. During the hypoglycemic clamp, plasma glucose decreased from 5.0 mmol/L
to 2.8 mmol/L for two periods of 120 minutes (mean glucose, 2.9 ± 0.03 and 2.8 ± 0.02
mmol/L, respectively) separated by a 60-minute interval of euglycemia (mean glucose,
4.7 ± 0.01 mmol/L). Seven subjects also had paired control studies in random order
during which a 330-minute euglycemic clamp (mean glucose, 5.0 ± 0.11 mmol/L) instead
of a hypoglycemic clamp was performed on day 2. Basal ACTH (4.6 ± 0.7 v 2.6 ± 0.4
pmol/L, P < .02) and basal cortisol (435 ± 46 v 317 ± 40 nmol/L, P < .02) both decreased from day 1 to day 3 following intervening hypoglycemia. In
contrast, with intervening euglycemia, neither basal ACTH (5.9 ± 1.5 v 4.5 ± 1.0 pmol/L)
nor basal cortisol (340 ± 38 v 318 ± 60 nmol/L) were reduced significantly on day
3 compared with day 1. Following interval hypoglycemia, the area under the curve (AUC)
for the cortisol response to successive ACTH infusions was increased (4,734 ± 428
nmol/L over 240 minutes [day 3] v 3,526 ± 434 nmol/L over 240 minutes [day 1], P < .01). The maximum incremental cortisol response was also significantly increased
(805 ± 63 nmol/L (day 3) v 583 ± 58 nmol/L (day 1), P < .05). In contrast, the AUC for the cortisol response to successive ACTH infusions with
interval euglycemia (3,402 ± 345 nmol/L over 240 minutes [day 3] v 3,709 ± 391 nmol/L
over 240 minutes [day 1] and the incremental cortisol response (702 ± 62 nmol/L [day
3] v 592 ± 85 nmol/L [day 1] were unchanged. Following exposure to intermittent hypoglycemia
in healthy humans, fasting morning ACTH and cortisol levels are reduced and the incremental
cortisol response to an infusion of ACTH is enhanced. The enhanced cortisol response
to exogenous ACTH infusion after intervening hypoglycemia (but not intervening euglycemia)
may reflect priming of the adrenal gland by endogenous ACTH produced during the hypoglycemia.
These data suggest that adrenal function testing by exogenous ACTH administration
is not impaired by prior exposure to hypoglycemia. Moreover, the reduced cortisol
response to recurrent hypoglycemia in patients with well-controlled diabetes is not
likely the result of impaired adrenal responsiveness.
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Article info
Publication history
Accepted:
April 10,
1998
Received:
December 20,
1997
Footnotes
☆Supported in part by a grant from the Dicker Fund (C.K.W.), a fellowship grant from the Juvenile Diabetes Foundation International (B.T.K.), a Cancer Development Award from the American Diabetes Association (B.T.K.), a grant from the Adler Foundation (D.C.S.), and National Institutes of Health Grants No. DK-36836 (Diabetes and Endocrinology Research Center at Joslin Diabetes Center) and RR-02635 (General Clinical Research Center at Brigham and Women's Hospital).
☆☆Presented in part at the 77th Annual Meeting of the Endocrine Society, Washington, DC, June 14–17, 1995.
Identification
Copyright
© 1998 Published by Elsevier Inc.
