Hypoglycemia Associated Autonomic Failure in Type 1 DM, Q5

December 10, 2014 updated by: Steve Davis, Vanderbilt University

Hypoglycemia Associated Autonomic Failure in Type 1 DM, Question 5

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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
Drug: epinephrine
Epinephrine 0.06 µg/kg/min infusion during hyperinsulinemic euglycemic clamp 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 infused over two hours during experimental period on Day 2
Drug: epinephrine
Epinephrine 0.06 µg/kg/min infusion during hyperinsulinemic euglycemic clamp on day 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
catecholamine levels
Time Frame: 2 days
2 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

January 18, 2008

First Submitted That Met QC Criteria

January 18, 2008

First Posted (Estimate)

January 31, 2008

Study Record Updates

Last Update Posted (Estimate)

December 11, 2014

Last Update Submitted That Met QC Criteria

December 10, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB #040911- HAAF in T1DM, Q5
  • R01DK069803-03 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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