Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

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

doi:10.1056/NEJM198708133170705

Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

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

^*Corresponding author af dette arbejde

52 Citationer (Scopus)

Abstract

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…

Originalsprog	Engelsk
Tidsskrift	New England Journal of Medicine
Vol/bind	317
Udgave nummer	7
Sider (fra-til)	421-426
Antal sider	6
ISSN	0028-4793
DOI	https://doi.org/10.1056/NEJM198708133170705
Status	Udgivet - 1987

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title = "Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy",

abstract = "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…",

keywords = "Faculty of Science, Adrenalin, Beta adrenergic receptor, Fatty acid, Glucose, Glycerol, Lactic acid",

author = "Jannik Hilsted and Erik Richter and Sten Madsbad and Bente Tronier and Christensen, {Niels Juel} and Per Hildebrandt and Meta Damkj{\ae}r and Henrik Galbo",

year = "1987",

doi = "10.1056/NEJM198708133170705",

language = "English",

volume = "317",

pages = "421--426",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "7",

}

TY - JOUR

T1 - Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

AU - Hilsted, Jannik

AU - Richter, Erik

AU - Madsbad, Sten

AU - Tronier, Bente

AU - Christensen, Niels Juel

AU - Hildebrandt, Per

AU - Damkjær, Meta

AU - Galbo, Henrik

PY - 1987

Y1 - 1987

N2 - 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…

AB - 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…

KW - Faculty of Science

KW - Adrenalin

KW - Beta adrenergic receptor

KW - Fatty acid

KW - Glucose

KW - Glycerol

KW - Lactic acid

U2 - 10.1056/NEJM198708133170705

DO - 10.1056/NEJM198708133170705

M3 - Journal article

AN - SCOPUS:0023177945

SN - 0028-4793

VL - 317

SP - 421

EP - 426

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 7

ER -

Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy

Abstract

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