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Ischemic Injury and Ischemic Preconditioning in Diabetes

This study has been completed.
Dutch Diabetes Fund
Information provided by:
Radboud University Identifier:
First received: September 9, 2005
Last updated: April 4, 2007
Last verified: April 2007

In this proof-of-concept study, forearm vulnerability to ischemic exercise is studied in patients with type 1 diabetes mellitus with and without prior ischemic preconditioning (short period of ischemia that protects against subsequent ischemic exercise). Annexin A5 scintigraphy is used to quantify subtle signs of mild and reversible forearm injury that results from ischemic exercise.

The following hypotheses are tested:

  1. Patients with type 1 diabetes are not more vulnerable to ischemic injury as compared with previously studied healthy volunteers.
  2. Ischemic preconidtioning is still present in patients with type 1 diabetes. Depending on the validity of hypothesis 2, the effect of short pharmacological interventions are studied on vulnerability to forearm ischemia/reperfusion injury in the absence or presence of local forearm ischemic preconditioning.

Condition Intervention
Diabetes Mellitus, Insulin-Dependent
Ischemia-Reperfusion Injury
Procedure: Ischemic preconditioning
Procedure: Forearm ischemic exercise
Procedure: Annexin A5 scintigraphy
Drug: Diazoxide
Drug: glibenclamide
Drug: adenosine

Study Type: Observational
Study Design: Observational Model: Defined Population
Primary Purpose: Screening
Time Perspective: Cross-Sectional
Time Perspective: Prospective
Official Title: Acute Local Ischemic Preconditioning in Patients With Type 1 Diabetes in Vivo

Resource links provided by NLM:

Further study details as provided by Radboud University:

Estimated Enrollment: 20
Study Start Date: June 2004
Study Completion Date: May 2005
Detailed Description:

All patients will be studied in supine position after an overnight fast, while plasma glucose levels are monitored. In the first 8 patients intravenous insulin is administered as needed, to reach target glucose levels between 5-7 mmol/l. Patients will be subjected to 10 minutes of forearm ischemia (non-dominant arm), combined with handgripping at 50% of maximal force until exhaustion. Upon reperfusion, Tc-99m-HYNIC-Annexin A5 will be injected intravenously. Targeting of annexin A5 to thenar muscle and forearm flexor muscle will be quantified as the percentage difference in radioactivity between experimental and control side. This procedure will be performed twice (randomized cross-over design), with at least 2 week interval, either with or without 10 minutes ischemia followed by 10 minutes of reperfusion prior to ischemic exercise.

Depending on the results of this study, substudies will be performed to study the effect of diazoxide (K-ATP channel opener, may mimic ischemic preconditioning), glibenclamide (K-ATP channel blocker, may inhibit ischemic preconditioning) or adenosine (infusion into brachial artery of non-dominant arm as a substitute for ischemic preconditioning).


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • type 1 diabetes mellitus
  • age 18-50 years

Exclusion Criteria:

  • hypertension (systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg
  • cardiovascular disease (coronary artery insufficiency,CVA/TIA, peripheral artery disease
  • HbA1c > 9%
  • Body Mass Index < 25 kg/m2
  • Unable to stop co-medication (other than insulin) for 1 week
  • Previous exposure to radiation (diagnostic or therapeutic) in the past year
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Please refer to this study by its identifier: NCT00184821

Clinical Research Centre Nijmegen; Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Dutch Diabetes Fund
Study Chair: Richard Engbersen, MD Radboud University Nijmegen Medical Centre; department of Pharmacology-Toxicology
Study Chair: Gerard Rongen, MD, PhD Radboud University Nijmegen Medical Centre; Department of Pharmacology-Toxicology
Study Chair: Wim Oyen, MD, PhD Radboud University Nijmegen Medical Centre; Department of Nuclear Medicine
Study Chair: Marc Mol, MD, PhD Canisius Wilhelmina Ziekenhuis Nijmegen; Department of Internal Medicine
Principal Investigator: Paul Smits, MD, PhD Radboud University Nijmegen Medical Centre; Department of Pharmacology-Toxicology
Study Chair: B. Bravenboer, MD, PhD Catharina Hospital Eindhoven, Dept. of Internal Medicine
  More Information

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00184821     History of Changes
Other Study ID Numbers: QKF03-diab
Study First Received: September 9, 2005
Last Updated: April 4, 2007

Keywords provided by Radboud University:
Annexin A5 scintigraphy

Additional relevant MeSH terms:
Diabetes Mellitus
Reperfusion Injury
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Autoimmune Diseases
Immune System Diseases
Annexin A5
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Hypoglycemic Agents processed this record on April 24, 2017