α‑Glucosidase inhibitor miglitol attenuates glucose fluctuation, heart rate variability and sympathetic activity in patients with type 2 diabetes and acute coronary syndrome : a multicenter randomized controlled (MACS) study

Background: Little is known about clinical associations between glucose fluctuations including hypoglycemia, heart rate variability (HRV), and the activity of the sympathetic nervous system (SNS) in patients with acute phase of acute coronary syndrome (ACS). This pilot study aimed to evaluate the short-term effects of glucose fluctuations on HRV and SNS activity in type 2 diabetes mellitus (T2DM) patients with recent ACS. We also examined the effect of suppressing glucose fluctuations with miglitol on these variables. Methods: This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group comparative study included 39 T2DM patients with recent ACS, who were randomly assigned to either a miglitol group (n = 19) or a control group (n = 20). After initial 24-h Holter electrocardiogram (ECG) (Day 1), miglitol was commenced and another 24-h Holter ECG (Day 2) was recorded. In addition, continuous glucose monitoring (CGM) was performed throughout the Holter ECG. Results: Although frequent episodes of subclinical hypoglycemia (≤4.44 mmo/L) during CGM were observed on Day 1 in the both groups (35% of patients in the control group and 31% in the miglitol group), glucose fluctuations were decreased and the minimum glucose level was increased with substantial reduction in the episodes of subclinical hypoglycemia to 7.7% in the miglitol group on Day 2. Holter ECG showed that the mean and maximum heart rate and mean LF/HF were increased on Day 2 in the control group, and these increases were attenuated by miglitol. When divided 24-h time periods into day-time (0700–1800 h), night-time (1800–0000 h), and bed-time (0000–0700 h), we found increased SNS activity during day-time, increased maximum heart rate during night-time, and glucose fluctuations during bed-time, which were attenuated by miglitol treatment. Conclusions: In T2DM patients with recent ACS, glucose fluctuations with subclinical hypoglycemia were associated with alterations of HRV and SNS activity, which were mitigated by miglitol, suggesting that these pathological relationships may be a residual therapeutic target in such patients

Translocator protein imaging with 18F-FEDAC-positron emission tomography in rabbit atherosclerosis and its presence in human coronary vulnerable plaques

Background and aims: This study aimed to investigate whether N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[18F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide (18F-FEDAC), a probe for translocator protein (TSPO), can visualize atherosclerotic lesions in rabbits and whether TSPO is localized in human coronary plaques.Methods: 18F-FEDAC-PET of a rabbit model of atherosclerosis induced by a 0.5% cholesterol diet and ballooninjury of the left carotid artery (n = 7) was performed eight weeks after the injury. The autoradiography intensity of 18F-FEDAC in carotid artery tissue sections was measured, and TSPO expression was evaluated immunohistochemically.TSPO expression was examined in human coronary arteries obtained from autopsy cases (n = 16), and in human coronary plaques (n = 12) aspirated from patients with acute myocardial infarction (AMI).Results: 18F-FEDAC-PET visualized the atherosclerotic lesions in rabbits as high-uptake areas, and the standard uptake value was higher in injured arteries (0.574 ± 0.24) than in uninjured arteries (0.277 ± 0.13, p < 0.05) or myocardium (0.189 ± 0.07, p < 0.05). Immunostaining showed more macrophages and more TSPO expression in atherosclerotic lesions than in uninjured arteries. TSPO was localized in macrophages, and arterial autoradiography intensity was positively correlated with macrophage concentration (r = 0.64) and TSPO (r = 0.67). TSPO expression in human coronary arteries was higher in AMI cases than in non-cardiac death, or in the vulnerable plaques than in early or stable lesions, respectively. TSPO was localized in macrophages in all aspirated coronary plaques with thrombi.Conclusions: 18F-FEDAC-PET can visualize atherosclerotic lesions, and TSPO-expression may be a marker of highrisk coronary plaques

Development of a Laboratory Risk-Score Model to Predict One-Year Mortality in Acute Myocardial Infarction Survivors

The high post-discharge mortality rate of acute myocardial infarction (AMI) survivors is concerning, indicating a need for reliable, easy-to-use risk prediction tools. We aimed to examine if a combined pre-procedural blood testing risk model predicts one-year mortality in AMI survivors. Overall, 1355 consecutive AMI patients who received primary coronary revascularization were divided into derivation (n = 949) and validation (n = 406) cohorts. A risk-score model of parameters from pre-procedural routine blood testing on admission was generated. In the derivation cohort, multivariable analysis demonstrated that hemoglobin &lt; 11 g/dL (odds ratio (OR) 4.01), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (OR 3.75), albumin &lt; 3.8 mg/dL (OR 3.37), and high-sensitivity troponin I &gt; 2560 ng/L (OR 3.78) were significantly associated with one-year mortality after discharge. An increased risk score, assigned from 0 to 4 points according to the counts of selected variables, was significantly associated with higher one-year mortality in both cohorts (p &lt; 0.001). Receiver-operating characteristics curve analyses of risk models demonstrated adequate discrimination between patients with and without one-year death (area under the curve (95% confidence interval) 0.850 (0.756&ndash;0.912) in the derivation cohort; 0.820 (0.664&ndash;0.913) in the validation cohort). Our laboratory risk-score model can be useful for predicting one-year mortality in AMI survivors