Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

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Jannik Hilsted, Erik Richter, Sten Madsbad, Bente Tronier, Niels Juel Christensen, Per Hildebrandt, Meta Damkjær, Henrik Galbo

Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients. To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 μg per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients with autonomic neuropathy (P<0.01) but was unchanged in the other groups. Since cardiac output increased to a similar extent in the three groups, the decrease in blood pressure was due to a significantly larger decrease (P<0.01) in total peripheral vascular resistance in the patients with autonomic neuropathy. The heart rate increased significantly more during the infusions in the patients with neuropathy than in those without neuropathy. Epinephrine produced a greater increase in blood glucose, the glucose-appearance rate, lactate, glycerol, and free fatty acids in the patients with autonomic neuropathy than in the other groups (P<0.05). These findings indicate that several beta-receptor–mediated responses to epinephrine are enhanced in patients with diabetic autonomic neuropathy. The underlying mechanism remains to be elucidated. (N Engl J Med 1987; 317:421–6.), IN patients with diabetic autonomic neuropathy1 , 2 or autonomic neuropathies of other origins,3 , 4 vascular sensitivity to alpha-adrenergic agonists such as norepinephrine is increased. This effect may be due to denervation hypersensitivity following the degeneration of sympathetic nerves. During infusion of beta-receptor agonists, the heart-rate response is increased in patients with autonomic neuropathy.5 6 7 In contrast, the effect of beta-receptor stimulation on hormonal, metabolic, and vascular responses has not been studied directly. Indirect evidence suggests that the sensitivity of beta-receptor–mediated responses to circulating epinephrine may be increased in patients with diabetic autonomic neuropathy. For example, during hypoglycemia, glucose counterregulation depends on the secretion…

Original languageEnglish
JournalNew England Journal of Medicine
Volume317
Issue number7
Pages (from-to)421-426
Number of pages6
ISSN0028-4793
DOIs
Publication statusPublished - 1987

    Research areas

  • Faculty of Science - Adrenalin, Beta adrenergic receptor, Fatty acid, Glucose, Glycerol, Lactic acid

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