AimsType 2 diabetes is preceded by a symptom-free period of impaired glucose tolerance (IGT). Pancreatic B-cell function decreases as glucose intolerance develops. In many patients with IGT, fasting blood glucose is within normal limits and hyperglycaemia occurs only postprandially. We examined whether pancreatic B-cell function changes during acute hyperglycaemia induced by oral glucose loading.MethodsWe calculated the insulinogenic index (I.I.) as an indicator of pancreatic B-cell function and measured serum levels of thioredoxin, a marker of cellular redox state, and 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative stress, during a 75-g oral glucose tolerance test (OGTT) in 45 subjects [24 patients with normal glucose tolerance (NGT), 14 with IGT and seven with Type 2 diabetes].ResultsThioredoxin levels decreased after glucose loading [66.1 ± 23.7, *59.3 ± 22.4, *49.3 ± 21.2 and *37.7 ± 18.0 ng/mL, fasting (0 min) and at 30, 60 and 120 min, respectively; *P < 0.001 vs. fasting]. In contrast, concentrations of 8-OHdG peaked at 30 min and then gradually decreased (0.402 ± 0.123, *0.440 ± 0.120, †0.362 ± 0.119 and †0.355 ± 0.131 ng/mL, *P < 0.05 vs. fasting, †P < 0.01 vs. 30 min). The insulinogenic index correlated with the change in thioredoxin levels (r = 0.34, P < 0.05). However, there was no relationship with the change in 8-OHdG levels from 0 to 30 min.ConclusionsHyperglycaemia in response to oral glucose impairs pancreatic B-cell function with decreasing thioredoxin levels. The augmented oxidative stress induced by hyperglycaemia may affect the cellular redox state. These findings strongly suggest that repeated postprandial hyperglycaemia may play an important role in the development and progression of diabetes mellitus.
yocardial reperfusion is necessary for the salvage and recovery of the ischemic myocardium. Early reperfusion therapy has improved the clinical outcomes of patients with acute myocardial infarction (AMI), but these benefits are limited in some patients by reperfusion injuries. 1 There is now increasing evidence that reactive oxygen species (ROS) lead to reperfusion injuries in the ischemic myocardium and that they are related to subsequent left ventricular (LV) dysfunction. 2,3 Recent investigations have shown that increased vascular oxidative stress predicts the risk of cardiovascular events in patients with coronary artery disease. 4 Various different radical scavengers and antioxidants have been shown to effectively reduce reperfusion injury in experimental models. 5,6 In these ischemia-reperfusion models, it was demonstrated that radical scavengers such as superoxide dismutase and vitamin E analog reduced infarct size by limiting reperfusion-induced oxidative stress and by attenuating the inflammatory response. On the basis of this established scientific rationale, several randomized controlled trials were designed to prove or disprove the causative effects for antioxidant supplements. 7-10 Unfortunately, results of these studies on antioxidants and cardiovascular event risks have been disappointing, especially in regards to the studies investigating primary prevention. Namely, each study has several limitations to test therapeutic agents in clinical practice, mainly because of their low accessibility to tissue or rapid clearance from the body. 11,12 In contrast, edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), has a low molecular weight (174.20 kD), is lipophilic, and is readily accessible to tissue. 13,14 Edaravone has the ability to scavenge toxic free radicals; moreover, it has been shown to inhibit vascular endothelial cell injury and to inhibit the aggravation of brain edema caused by free radical-induced lipid peroxidation. 15 Recently, edaravone has been officially approved for the treatment of acute ischemic stroke in Japan. 16 Previous experimental studies have reported that the administration of edaravone just before reperfusion reduced reperfusion injuries and myocardial damage in myocardial ischemia-reperfusion animal models. 17,18 Edaravone has been shown to attenuate pressure overload-induced LV hypertrophy via its antioxidant function according to a recent report. 19 With these effects, edaravone has been recognized as both a potent cardioprotective and a cytoprotective agent. We have recently demonstrated that the administration of edaravone just prior to myocardial reperfusion attenuated both enzymatic infarct size and reperfusion arrhythmia in patients with AMI; 20 however, its effects on long-term clinical outcomes in AMI patients have not yet been clarified. The purpose of the present study was to clarify the efficacy of edaravone on the long-term prognosis in patients with AMI. Long-Term Efficacy of Edaravone in Patients With Acute Myocardial InfarctionKenichi Tsujita, MD; Hideki Shimo...
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