Improved Erythrocyte Deformability Induced by Sodium-Glucose Cotransporter 2 Inhibitors in Type 2 Diabetic Patients.

PURPOSE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are antidiabetic drugs that improve cardiovascular outcomes. Hemoglobin and hematocrit values increase after SGLT-2 inhibitor administration. Although these factors increase blood viscosity and the risk of cardiovascular disease, SGLT-2 inhibitors have protective effects on the cardiovascular system. The mechanisms for this paradoxical phenomenon remain unclear, and the effect of SGLT-2 inhibitors on hemorheology has not been studied. METHODS: We evaluated the hemorheological parameters of 63 patients of whom 38 received metformin with a dipeptidyl peptidase 4 (DPP-4) inhibitor, while 25 received metformin with SGLT-2 inhibitor. Blood viscosity was measured using a cone-and-plate viscometer, erythrocyte aggregation was measured using a modified erythrocyte sedimentation rate method, and erythrocyte membrane fluctuation was measured as deformability, using a diffraction optical tomography. RESULTS: Both blood viscosity and erythrocyte aggregation increased in the SGLT-2 inhibitor group, although erythrocyte deformability was significantly improved compared with that of the DPP-4 inhibitor group (DPP-4 inhibitor 43.71 ± 5.13 nm; SGLT-2 inhibitor 53.88 ± 4.88 nm; p < 0.001). When the two groups were compared after propensity score matching, no differences in blood viscosity at high shear rates and erythrocyte aggregation were observed, although erythrocyte deformability was significantly improved in the SGLT-2 inhibitor group (DPP-4 inhibitor 45.01 ± 5.28 nm; SGLT-2 inhibitor 53.14 ± 4.72 nm; p = 0.001). CONCLUSION: This study demonstrates that erythrocyte deformability was improved in the SGLT-2 inhibitor group compared with that in the DPP-4 inhibitor group. This improvement in erythrocyte deformability is expected to have a protective effect on the cardiovascular system.

Effects of osmolality and solutes on the morphology of red blood cells according to three-dimensional refractive index tomography.

Phosphate-buffered saline (PBS) and Alsever's solution (AS) are frequently used as media in blood-related studies, while 0.9% normal saline (NS) is frequently used in transfusion medicine. Despite the frequent use, the effects of these solutions on the shape and volume of red blood cells (RBCs) have not been reported. We collected blood samples from five healthy adults and used three-dimensional refractive index tomography to investigate the changes in the morphology of RBCs caused by changes in osmolality and solutes at the single-cell level. After diluting 2 µL of RBCs 200-fold with each solution (PBS, AS, and 0.9% NS), 40 randomly selected RBCs were microscopically observed. RBC shape was measured considering sphericity, which is a dimensionless quantity ranging from 0 (flat) to 1 (spherical). RBCs in plasma or AS showed a biconcave shape with a small sphericity, whereas those in 0.9% NS or PBS showed a spherical shape with a large sphericity. Moreover, we confirmed that sodium chloride alone could not elicit the biconcave shape of RBCs, which could be maintained only in the presence of an osmotic pressure-maintaining substance, such as glucose or mannitol. Although 0.9% NS solution is one of the most commonly used fluids in hematology and transfusion medicine, RBCs in 0.9% NS or PBS are not biconcave. Therefore, as the debate on the use of NS continues, future clinical studies or applications should consider the effect of glucose or mannitol on the shape of RBCs.

Temperature Correction to Enhance Blood Glucose Monitoring Accuracy Using Electrical Impedance Spectroscopy.

Electrical methods are among the primarily studied non-invasive glucose measurement techniques; however, various factors affect the accuracy of the sensors used. Of these, the temperature is a critical factor; hence, the effects of temperature on the electrical properties of blood components are investigated in this study. Furthermore, the changes in the electrical properties of blood according to the glucose level are corrected by considering the effects of temperature on the electrical properties. An impedance sensor is developed and used to measure whole blood impedance in 10 healthy participants at various temperatures and glucose levels. Subsequently, the conductivities of the plasma and cytoplasm were extracted. Changes in the electrical properties of the blood components are then analyzed using linear regression and repeated measures ANOVA. The electrical conductivities of plasma and cytoplasm increased with increasing temperatures (plasma: 0.0397 (slope), 0.7814 (R2), cytoplasm: 0.014 (slope), 0.694 (R2)). At three values of increasing glucose levels (85.4, 158.1, and 271.8 mg/dL), the electrical conductivities of the plasma and cytoplasm decreased. These tendencies are more significant upon temperature corrections (p-values; plasma: 0.001, 0.001, cytoplasm: 0.003, 0.002). The relationships between temperature and electrical conductivity changes can thus be used for temperature corrections in blood glucose measurement.

Mental health impact on a humidifier disinfectant disaster victim: a case report.

In Korea, the cause of lung disease of unknown origin was identified as humidifier disinfectants in November 2011. In February 2017, the 'Special Act on Remedy for Damage Caused by Humidifier Disinfectants' was promulgated. Even though emotional and mental injuries caused by humidifier disinfectants have been reported, the focus of the special act has been on physical injury only, and criteria for recognizing mental health impact have not been considered. This case considers emotional and mental injury caused by humidifier disinfectants. After a humidifier disinfectant was used from January 2005 to April 2006, the patient's son aged 20 months was hospitalized with respiratory symptoms, and he died within two weeks. Also, the patient was hospitalized for a month with the same symptoms, and then she led a normal life with no symptoms. After both mother and son were diagnosed with definite (level 1) humidifier disinfectant lung injury (HDLI) in 2017, she took to drinking alcohol because of extreme guilt over her son's death. In March 2018 she died from acute liver failure due to alcohol use disorder. The patient's death was caused by continuous alcoholism, due to emotional and mental trauma caused by her son's death after HDLI was revealed as the cause. The government did not acknowledge her death was due to humidifier disinfectants, but the company that sold the humidifier disinfectants recognized her as a victim and compensated the family of the victim. There are still lots of psychological responses among humidifier disinfectant disaster victims. Mental health impact on humidifier disinfectant victims should be considered more carefully, and institutional improvements should be made into establish psychological interventions and measures.

A physiometer for simultaneous measurement of whole blood viscosity and its determinants: hematocrit and red blood cell deformability.

In this study, a microfluidic-based physiometer capable of measuring whole blood viscosity, hematocrit, and red blood cell (RBC) deformability on a chip is introduced. The physiometer consists of two major parts: a hydrodynamic component for whole blood viscosity measurement and an electronic component for hematocrit and RBC deformability measurement. In the hydrodynamic component, the whole blood is infused with phosphate buffered saline as a reference fluid for estimation of the whole blood viscosity. At a given flow rate, ten sets of whole blood viscosity readings are successfully obtained over a wide range of shear rates; this is achieved via a series of geometrically optimized microchannel arrays. In the electronic component, analysis of the whole blood impedance spectrum under flowing conditions reveals the electrical characteristics of the blood: the cytoplasm resistance (Rcytoplsm), plasma resistance (Rplasma), and RBC membrane capacitance (constant phase element). The hematocrit is estimated from Rcytoplsm and Rplasma, while the RBC deformation index is determined from the membrane capacitance change of the RBC. Each unique function is experimentally demonstrated and compared to the corresponding gold standard method. The whole blood viscosity measured using the physiometer is 0.8 ± 1.4% in normalized difference compared to that using a rotational cone-and-plate viscometer. For the hematocrit measurement, the coefficient of variation for the physiometer ranges from 0.3 to 1.2% which is lower than the one obtained from centrifugation. In the deformability measurement, there is a strong linear correlation (R2 = 0.97) between the deformation index acquired by image processing and the change in the membrane capacitance acquired by using the physiometer. The effects of the hematocrit and RBC deformability on the whole blood viscosity are also demonstrated. For simultaneous and reliable measurement on a chip, a physiometer equipped with a temperature-control system is prepared. Lab-made software enables the measurement of the three target indices and the temperature control in an automated manner. By using this system, the temperature is controlled to 36.9 ± 0.2 °C which greatly matches with the target temperature (37.0 °C) and it is varied from 25 °C to 43 °C. The developed physiometer is potentially applicable for a comprehensive analysis of biophysical indices in whole blood.