Effect of a hypoglycemic agent on ischemic preconditioning in patients with type 2 diabetes and stable angina pectoris

Objective Ischemic preconditioning is an increased tolerance to myocardial ischemia during the second of two consecutive exercise tests. ATP-sensitive K+ channel blockers, such as glinides and sulfonylurea drugs, can induce loss of ischemic preconditioning. This study aimed to investigate the effects of repaglinide, a hypoglycemic agent with an affinity for myocardial ATP-sensitive K+ channels, on the results of consecutive exercise tests in patients with diabetes and multivessel coronary artery disease. Methods Forty-two patients with type 2 diabetes and chronic stable angina pectoris, and two-vessel or three-vessel disease participated in this study. The patients underwent two consecutive treadmill exercise tests (phase 1). On the day after these exercise tests, 2 mg of oral repaglinide was given to the patients. One week later, two exercise tests were repeated consecutively (phase 2). Results All patients achieved 1.0-mm ST-segment depression during the four exercise tests (T1, T2, T3, and T4). In phase 2, seven patients improved in time to onset of 1.0-mm ST-segment depression. The worsening of the time to onset of 1.0-mm ST-segment depression in phase 2 demonstrated ischemic preconditioning block in 83.3% of patients (P=0.0001). Even the postexercise electrocardiographic parameters (ST-segment depression morphology and magnitude and arrhythmias) were significantly different between the groups with and without pharmacologic ischemic preconditioning block (P=0.031). Conclusions Repaglinide, an oral hypoglycemic agent with ATP-sensitive K+ channel-blocker activity, eliminated the myocardial ischemic preconditioning in patients with coronary disease and diabetes.