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Hypoglycemia Associated Autonomic Failure in Type 1 DM, Q5

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00605774
Recruitment Status : Withdrawn
First Posted : January 31, 2008
Last Update Posted : December 11, 2014
Information provided by (Responsible Party):
Steve Davis, Vanderbilt University

Brief Summary:
When a patient with Type 1 diabetes exercises, he or she is more prone to low blood sugar, or hypoglycemia. It is known that antecedent exercise can blunt defense responses, called counterregulatory responses to subsequent hypoglycemia in Type 1 DM, causing him or her to be vulnerable to another bout of hypoglycemia. Epinephrine is one of the important hormones in the defense of blood glucose during both exercise and hypoglycemia. We will test the hypothesis that antecedent exercise will blunt the metabolic, neuroendocrine and cardiovascular effects of subsequent epinephrine infusion in Type 1 DM.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Drug: epinephrine Not Applicable

Detailed Description:
We have recently performed studies to determine whether the critical metabolic actions of epinephrine are blunted in Type 1 DM. These studies have obvious clinical relevance because strategies aimed at increasing circulating levels of epinephrine will not be effective if the metabolic counterregulatory mechanisms (increased endogenous glucose production (EGP), increased lipolysis and reduced glucose uptake) of the hormone are also blunted. Epinephrine was infused to reach circulating levels of ~ 1000 pg/ml (This level of epinephrine is equivalent to values of the hormone observed during hypoglycemia of 50 mg/dl in healthy males and T1DM men with average glucose control) in groups of either intensively treated (HBA1C < 7.0%), conventionally treated (HBA1C > 9.0%) type 1 DM and age, weight matched healthy controls. In the intensively treated DM group, epinephrine's actions to increase EGP, lipolysis and to restrain glucose uptake were significantly reduced (<60%). The mechanism for our finding needs to be determined. Our hypothesis is that antecedent exercise can cause repetitive activations of Autonomic-adrenomedullary responses that lead to downregulation of β-adrenoreceptor mechanisms. Therefore, the combination of blunted epinephrine effects, increased insulin action and reduced levels of the catecholamine might fully explain the vexing clinical question of post exercise hypoglycemia in Type 1 DM. In this application, we will test the hypothesis that antecedent exercise will blunt the metabolic, neuroendocrine and cardiovascular effects of subsequent epinephrine infusion in Type 1 DM.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Official Title: Hypoglycemia Associated Autonomic Failure in Type 1 DM, Question 5

Arm Intervention/treatment
Experimental: 1
Hyperinsulinemic euglycemic glucose clamps x 2 on Day 1 Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion on Day 2
Drug: epinephrine
Epinephrine 0.06 µg/kg/min infused over two hours during experimental period on Day 2

Experimental: 2
Day 1 euglycemic exercise period x 2 Day 2 hyperinsulinemic euglycemic glucose clamp with epinephrine infusion
Drug: epinephrine
Epinephrine 0.06 µg/kg/min infusion during hyperinsulinemic euglycemic clamp on day 2

Primary Outcome Measures :
  1. catecholamine levels [ Time Frame: 2 days ]

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • 28 (14 males, 14 females) conventionally treated Type 1 diabetic patients with HA1C > 8.5%
  • 28 (14 males, 14 females) intensively treated Type 1 diabetic patients with HA1C < 7%
  • 28 (14 males, 14 females) non-diabetic controls
  • Age 18-45 yr.
  • Had diabetes for 2-15 years if diabetic subject
  • No clinical evidence of diabetic tissue complications, no cardiovascular disease
  • Body mass index 21-27kg · m-2
  • Normal bedside autonomic function
  • Normal results of routine blood test to screen for hepatic, renal, and hematological abnormalities
  • Female volunteers of childbearing potential: negative HCG pregnancy test

Exclusion Criteria:

  • Prior history of poor health: any current or prior disease condition that alters carbohydrate metabolism and prior cardiac events and/or evidence for cardiac disease
  • Hemoglobin of less than 12 g/dl
  • Abnormal results following screening tests
  • Pregnancy
  • Subjects unable to give voluntary informed consent
  • Subjects with a recent medical illness
  • Subjects with known liver or kidney disease
  • Subjects taking steroids
  • Subjects taking beta blockers
  • Subjects on anticoagulant drugs, anemic, or with known bleeding diseases

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00605774

Sponsors and Collaborators
Vanderbilt University
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Principal Investigator: Stephen N. Davis, MD Vanderbilt University

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Responsible Party: Steve Davis, Chairman of Medicine, University of Maryland, Baltimore, Vanderbilt University Identifier: NCT00605774     History of Changes
Other Study ID Numbers: IRB #040911- HAAF in T1DM, Q5
R01DK069803-03 ( U.S. NIH Grant/Contract )
First Posted: January 31, 2008    Key Record Dates
Last Update Posted: December 11, 2014
Last Verified: December 2014
Keywords provided by Steve Davis, Vanderbilt University:
Additional relevant MeSH terms:
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Pure Autonomic Failure
Glucose Metabolism Disorders
Metabolic Diseases
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Epinephryl borate
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Vasoconstrictor Agents