Abstract
BackgroundIn 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.Methods99mTechnetium-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.ResultsPatients 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.ConclusionsPatients 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 RegistrationThe study is registered at www.clinicaltrials.gov (NCT00184821)
Highlights
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
In the current study, we aimed to answer three research questions: 1) does T1DM affect the tolerance for ischemia reperfusion (IR)?; 2) does T1DM modulate the protective effect of ischemic preconditioning?; and 3) is the effect of T1DM on these parameters dependent on the plasma glucose and insulin concentrations?
Metabolic control during the experiment As intended, the two groups of patients with diabetes significantly differed with respect to plasma insulin and glucose concentrations
Summary
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. The most powerful intervention to limit myocardial infarct size, other than early coronary reperfusion, is ischemic preconditioning, which is defined as a reduction in infarct size by a preceding short period of myocardial ischemia [7] Based on this principle, alternative cardioprotective strategies have been developed, including remote preconditioning and pharmacological preconditioning [8]. These interventions protect the heart against IR injury, and other tissues including the kidney, the brain, the liver, and skeletal muscle It has been shown in animal models of myocardial infarction that various comorbidities, including hypercholesterolemia and diabetes, can limit the efficacy of these cardioprotective interventions [9]. In animal models of T1DM, studies on the effect of ischemic preconditioning on myocardial infarct size have yielded contradicting results [10]
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