Changes in glycemic variability, gastric emptying and vascular endothelial function after switching from twice-daily to once-weekly exenatide in patients with type 2 diabetes: a subpopulation analysis of the twin-exenatide study

Background We investigated the changes in blood glucose fluctuation, gastric emptying, and vascular endothelial function by switching from an exenatide twice-daily formulation (BID) to a once-weekly formulation (QW) since the evaluation of postprandial glucose excursion and glycemic variability (GV) by continuous glucose monitoring (CGM) after switching was lacking. Methods Twenty-nine patients with type 2 diabetes treated with exenatide BID were included in this study and switched to exenatide QW for 24 weeks. GV assessed by CGM, gastric emptying (by 13 C-acetate breath test) and vascular endothelial function (by reactive hyperemia - peripheral arterial tonometry) were evaluated at baseline and 24 weeks after switching. Results HbA1c decreased significantly from the baseline to week 24, while postprandial glucose levels after breakfast and dinner significantly increased (both P <0.05). However, the increases in GV indices were modest and not statistically significant at week 24. Vascular endothelial function was also not significantly changed after switching (P >0.05). Gastric emptying was significantly accelerated at week 24 (Tmax 83.4 ± 12.1 min vs. 58.2 ± 16.4 min) (P <0.001) and correlated with increased postprandial glucose levels after breakfast and dinner (both P <0.05). Conclusions Despite the increase in postprandial glucose associated with accelerated gastric emptying after switching from exenatide BID to QW, change in GV was modest and no significant deterioration in vascular endothelial function was observed after switching. These results support the superiority of treatment with exenatide QW over exenatide BID in clinical practice; however, attention should be paid to the monitoring and management of postprandial glucose levels when selecting exenatide QW. Trial registration Clinical trial registry number; UMIN000016390 and jRCTs031180320. Approval date of Registry and the Registration: December 12, 2014.

Association between serum placental growth factor and vascular endothelial function in hyprtensive disorders complicating pregnancy

Hypertensive disorders complicating pregnancy (HDCP) is a systemic disease among pregnant women. Therefore, the prevention and prediction of hypertension during pregnancy are critical. This study aimed to clarify whether the vascular endothelial function of women with gestational hypertension was linked to placental growth factor. A total of 200 pregnant women were enrolled in our study and subsequently divided into two groups: the HDCP group and the normal pregnancy controls. The levels of serum placental growth factor, as well as plasma endothelin-1 and nitric oxide, between the two groups were measured. In addition, the endothelial function indexes, including pressure-strain elasticity coefficient (EP), the common carotid stiffness index (β), arterial compliance, single-point pulsed-wave velocity, and augment index (AI) of bilateral common carotid arteries, were compared between the HDCP and control groups using the echo tracking technique. In our study, the level of placental growth factor in the HDCP group was significantly lower than the control group. Furthermore, our results clarified that endothelin-1 increased while nitric oxide decreased in the HDCP group compared with the control group. On the other hand, we found that EP, β, pulsed-wave velocity and augment index values were significantly higher in the HDCP group than in the control group (P < 0.001). However, the value of arterial compliance was significantly decreased in patients of the HDCP group compared with the control group (P < 0.001). In conclusion, the association between serum placental growth factor and vascular endothelial function in HDCP could serve as a more accurate predictive factor of pregnant hypertension.

Relationship between Quantitative Parameters of Echocardiography and Vascular Endothelial Function in Patients with Chronic Heart Failure and Its Predictive Value for Short-Term MACE Risk

Objective. To investigate the relationship between quantitative parameters of echocardiography and vascular endothelial function in patients with chronic heart failure (CHF) and the predictive value of short-term major adverse cardiovascular events (MACE). Methods. From February 2018 to February 2020, 86 CHF patients in our hospital were selected as the observation group, and 46 healthy subjects were selected as the control group during the same period. Quantitative parameters of echocardiography (left ventricular ejection fraction (LVEF), left ventricular short-axis shortening rate (FS), and ratio of peak flow velocity between early and late mitral valve diastole (E/A)) and endothelial function indexes (endothelin-1 (ET-1)/nitric oxide (NO)) were compared between the two groups. The correlation between quantitative parameters of echocardiography and vascular endothelial function in patients with CHF was analyzed. A logistic regression equation was used to analyze the risk factors of MACE in patients with CHF. The receiver operating characteristic curve (ROC) was used to analyze the predictive value of quantitative parameters of echocardiography and NO/ET-1 for the risk of MACE in patients with CHF. Result. LVEF, FS, and NO/ET-1 in the observation group were lower than those in the control group, while E/A was higher than that in the control group ( P < 0.05 ). In CHF patients, LVEF and FS were positively correlated with NO/ET-1, while E/A was negatively correlated with NO/ET-1 ( P < 0.05 ). Logistic regression analysis showed that the decrease of LVEF, FS, NO/ET-1, and E/A were risk factors for MACE ( P < 0.05 ) after adjusting for age, body mass index, and cardiac function grading. The AUC value of short-term MACE predicted by quantitative parameters of echocardiography and NO/ET-1 combined was 0.883, with a corresponding sensitivity of 86.21% and specificity of 73.13%. Conclusion. Quantitative parameters of echocardiography in CHF patients are related to vascular endothelial function, and their combination can effectively predict the risk of MACE in the near future, providing reference for clinical treatment.

Hypoglycemia Induces Vascular Endothelial Dysfunction in Subjects With Normal Glucose Tolerance

This prospective study determined the effects of hypoglycemic stimulation on vascular endothelial function in non-diabetic patients using reactive hyperemia peripheral arterial tonometry (RH-PAT). The study included non-diabetic patients who were hospitalized for an insulin tolerance test (ITT) for the diagnosis of hypoadrenocorticism or hypopituitarism. Vascular endothelial function was assessed using the reactive hyperemia index (RHI) measured by the RH-PAT. We also measured the levels of anterior pituitary hormone, adrenaline, noradrenaline, and dopamine at the time of hypoglycemia. The primary endpoint was a change in the RHI at 120 minutes after insulin administration. The study included 27 patients. ITT was associated with significant increases in systolic blood pressure, pulse rate, and the blood levels of adrenocorticotropic hormone, cortisol, growth hormone, adrenaline, noradrenaline, and dopamine. RHI significantly decreased after ITT from 2.24±0.51 to 1.71±0.42. A significant inverse correlation was observed between the change in RHI and change in adrenaline (r=-0.670, p=0.012). We concluded that hypoglycemic stimulation altered vascular endothelial function, as measured by RH-PAT, even in patients free of glucose intolerance. The observed deterioration in vascular endothelial function correlated with increases in catecholamine levels during hypoglycemia.Trial registration: UMIN000033244

Effect of Tirofiban Injection on vascular endothelial function, cardiac function and inflammatory cytokines in patients with acute myocardial infarction after emergency Percutaneous Coronary Intervention

Objectives: To evaluate the effect of tirofiban injection on vascular endothelial function, cardiac function, inflammatory cytokines and other indicators in patients with acute myocardial infarction after emergency PCI and its clinical significance. Methods: Eighty patients with acute myocardial infarction admitted to Affiliated Hospital of Hebei University from March 18, 2020 to October 18, 2020 were enrolled and randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. Patients in both groups underwent PCI. Patients in the control group were given oxygen inhalation, monitoring, and basic medications for myocardial infarction, such as nutritional myocardial drugs, statins, aspirin, nitrates, clopidogrel, and β-blockers. In contrast, patients in the experimental group received tirofiban 10 ug/kg intravenously over 5min immediately before PCI in addition to basic treatment, and then tirofiban 0.1 ug/(kg/min) was pumped via intravenous pump postoperatively for 48 hour. The changes of vascular endothelial function, cardiac function and adverse drug reactions (ADRs) in the two groups before treatment, one week and one month after treatment, as well as changes of inflammatory cytokines such as CRP and IL-6 in the two groups before and after treatment were compared and analyzed. Results: Compared with the control group, FMD, NO, ET-1 and other indexes in the experimental group were significantly improved one week and one month after treatment, with statistically significant differences (p<0.05). BNP, LVEDD, LVEF and additional indexes in the experimental group were significantly lower than those in the control group at one week and one month after treatment, with statistically significant differences (p=0.00). Moreover, the incidence of ST-segment fallback > 70% in the experimental group was 72.5% after treatment, which was significantly better than that of 47.5% in the control group, with a statistically significant difference (p=0.03). CRP and IL-6 in the experimental group were significantly lower than those in the control group after treatment, with a statistically significant difference (p=0.00). There was no statistical significance in the incidence of ADRs between the two groups after treatment (p=0.42). Conclusion: Tirofiban injection after emergency PCI is a beneficial treatment regime for patients with STEMI. With such a treatment regime, cardiac function and vascular endothelial function of patients can be dramatically improved, coronary blood supply will be ameliorated, inflammatory cytokines can be reduced, and no significant increase can be seen in the incidence of adverse reactions. doi: https://doi.org/10.12669/pjms.38.1.4413 How to cite this:Kang S, Meng X, Li J. Effect of Tirofiban Injection on vascular endothelial function, cardiac function and inflammatory cytokines in patients with acute myocardial infarction after emergency Percutaneous Coronary Intervention. Pak J Med Sci. 2022;38(1):---------. doi: https://doi.org/10.12669/pjms.38.1.4413 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Non-Invasive Detection of Fetal Vascular Endothelial Function in Gestational Diabetes Mellitus

ObjectivesEndothelial dysfunction in the fetuses of women with gestational diabetes mellitus (GDM) is associated with their subsequent cardiovascular events. Prenatal assessment of endothelial function in fetuses exposed to intrauterine hyperglycemic environment remains challenging. The aim of this study was to assess the fetal vascular endothelial function in GDM patients using color M-mode derived aortic propagation velocity (APV) and evaluate the correlation of APV with endothelial function biomarkers.MethodsThis observational cross-sectional study included 31 gestational diabetic mothers and 30 healthy pregnant mothers from August 2019 to January 2020. Clinical data were compared between the groups. Fetal APV was measured using color M-mode echocardiography at late gestation. Concentrations of endothelial biomarkers including von Willebrand Factor (vWF), vascular endothelial-cadherin and endothelin-1 in umbilical cord serum were assessed. Measurements between diabetic group and controls were compared.ResultsvWF was the only endothelial functional marker that differed between the two groups. Fetuses in the GDM group had significantly lower APV levels and higher vWF levels compared with the healthy controls (P &lt; 0.05). There was a moderate but significant correlation between APV and vWF (r =−0.58, P &lt; 0.001). There were no associations between APV and ventricular wall thickness or umbilical artery pulsatility index.ConclusionsColor M-mode propagation velocity of aorta is a non-invasive, practical method that correlates well with GDM and fetal endothelial function. This novel metric could contribute to recognizing early vascular functional alterations and hence represents a potential strategy for early risk factor surveillance and risk modification.