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Open Access Original investigation

Improved resistance to ischemia and reperfusion, but impaired protection by ischemic preconditioning in patients with type 1 diabetes mellitus: a pilot study

Richard Engbersen15, Niels P Riksen12*, Marc J Mol6, Bert Bravenboer7, Otto C Boerman3, Patrick Meijer14, Wim JG Oyen3, Cees Tack2, Gerard A Rongen12 and Paul Smits12

Author Affiliations

1 Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands

2 General Internal Medicine, Nijmegen, The Netherlands

3 Nuclear Medicine, Nijmegen, The Netherlands

4 Department of Anesthesiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

5 Slingeland Hospital, Doetinchem, Netherlands

6 Canisius Wilhelmina Hospital, Nijmegen, The Netherlands

7 Catharina Hospital, Eindhoven, the Netherlands

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Cardiovascular Diabetology 2012, 11:124  doi:10.1186/1475-2840-11-124

Published: 10 October 2012

Abstract

Background

In patients with type 1 diabetes mellitus (T1DM), cardiovascular events are more common, and the outcome following a myocardial infarction is worse than in nondiabetic subjects. Ischemic or pharmacological preconditioning are powerful interventions to reduce ischemia reperfusion (IR)-injury. However, animal studies have shown that the presence of T1DM can limit these protective effects. Therefore, we aimed to study the protective effect of ischemic preconditioning in patients with T1DM, and to explore the role of plasma insulin and glucose on this effect.

Methods

99mTechnetium-annexin A5 scintigraphy was used to detect IR-injury. IR-injury was induced by unilateral forearm ischemic exercise. At reperfusion, Tc-annexin A5 was administered, and IR-injury was expressed as the percentage difference in radioactivity in the thenar muscle between the experimental and control arm 4 hours after reperfusion. 15 patients with T1DM were compared to 21 nondiabetic controls. The patients were studied twice, with or without ischemic preconditioning (10 minutes of forearm ischemia and reperfusion). Patients were studied in either normoglycemic hyperinsulinemic conditions (n = 8) or during hyperglycemic normoinsulinemia (n = 7). The controls were studied once either with (n = 8) or without (n = 13) ischemic preconditioning.

Results

Patients with diabetes were less vulnerable to IR-injury than nondiabetic healthy controls (12.8 ± 2.4 and 11.0 ± 5.1% versus 27.5 ± 4.5% in controls; p < 0.05). The efficacy of ischemic preconditioning to reduce IR-injury, however, was lower in the patients and was even completely abolished during hyperglycemia.

Conclusions

Patients with T1DM are more tolerant to forearm IR than healthy controls in our experimental model. The efficacy of ischemic preconditioning to limit IR-injury, however, is reduced by acute hyperglycemia.

Trial Registration

The study is registered at www.clinicaltrials.gov (NCT00184821)

Keywords:
Type 1 diabetes; Ischemia-reperfusion injury; Ischemic preconditioning; Hyperglycemia; Annexin A5