Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Hypoglycemia Associated Autonomic Failure in Type 1 DM, Q5

This study has been withdrawn prior to enrollment.
Information provided by (Responsible Party):
Steve Davis, Vanderbilt University Identifier:
First received: January 18, 2008
Last updated: December 10, 2014
Last verified: December 2014
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 Intervention
Type 1 Diabetes
Drug: epinephrine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Hypoglycemia Associated Autonomic Failure in Type 1 DM, Question 5

Resource links provided by NLM:

Further study details as provided by Vanderbilt University:

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

Enrollment: 0
Arms Assigned Interventions
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

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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00605774

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

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 ( US NIH Grant/Contract Award Number )
Study First Received: January 18, 2008
Last Updated: December 10, 2014

Keywords provided by Vanderbilt University:

Additional relevant MeSH terms:
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 processed this record on April 26, 2017