Beyond their metabolic effect, sodium–glucose cotransporter-2 (SGLT-2) inhibitors reduce the risk of heart failure and have cardiovascular and nephroprotective effects, yet their exact mechanism of action remains unclear. This prospective study included 40 patients with type 2 diabetes whose physician initiated SGLT-2 inhibitor therapy. Prior to and 4 weeks after the initiation of SGLT-2 inhibitors, in addition to routine clinical and laboratory measurements, hydroxyl free radical and neuropathic evaluations were performed. Body weight, body mass index (BMI), fasting glucose, fructosamine, and albuminuria decreased significantly, whereas red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), and platelet count increased significantly. Urinary o-tyrosine/p-tyrosine and (m-tyrosine+o-tyrosine)/p-tyrosine ratios were significantly reduced, suggesting diminished hydroxyl free radical production. Patients with neuropathy, identified by abnormal baseline current perception threshold (CPT) values, showed significant improvements. Significant correlations between RBCs, platelet parameters, albuminuria, and hydroxyl free radical markers disappeared after SGLT-2 treatment and changes in hydroxyl free radical markers correlated positively with CPT changes. Our results suggest that short-term SGLT-2 inhibition recalibrates metabolic, hematologic, renal, and neuropathic endpoints simultaneously, presumably through attenuating abnormal ortho- and meta-tyrosine incorporation into signaling proteins. Further studies are required to confirm long-term durability and examine whether additional strategies, such as supplementation of the physiological p-tyrosine, could amplify these benefits.

Background: Chronic hemodialysis (HD) patients have a very high cardiovascular risk. Acute vascular changes during dialysis mediated by factors of the endothelium may have a crucial role in this. The aim of this article is to study the acute vascular changes during HD. Methods: In 29 consecutive chronic HD patients (age: 65.6 ± 10.4 years), their pre-, mid-, and post-HD plasma syndecan-1 (SDC-1) and endothelin-1 (ET-1) levels were measured. Applanation tonometry was performed before HD. Results: Their SDC-1 levels increased during HD (p = 0.004). Males had higher ET-1 levels. The patients were divided into two groups based on their pre-HD pulse wave velocity (PWV): PWV ≥ 12 m/s and PWV < 12 m/s. The pre-HD and mid-HD SDC-1 levels were higher in the group with a PWV ≥ 12 m/s (10.174 ± 2.568 vs. 7.928 ± 1.794 ng/mL, p = 0.013, and 10.319 ± 3.482 vs. 8.248 ± 1.793 ng/mL, p = 0.044, respectively). The post-HD ET-1 levels were higher in the patient group with a PWV ≥ 12 m/s (10.88 ± 3.00 vs. 8.05 ± 3.48 pg/l, p = 0.027). Patients with a PWV ≥ 12 m/s had higher pre-HD peripheral and aortic systolic blood pressures (p < 0.05). The total cholesterol correlated with the SDC-1 decrease during HD (r = 0.539; p = 0.008). The pre-, mid-, and post-HD SDC-1 correlated with ultrafiltration (r = 0.432, p = 0.019; r = 0.377, p = 0.044; and r = 0.401, p = 0.012, respectively). Conclusion: SDC-1 and ET-1 contribute to the vascular changes observed during HD, and they have correlations with some cardiovascular risk factors.

COVID-19 infection may lead to serious complications, e.g., need for mechanical ventilation or death in some cases. A retrospective analysis of patients referred to our COVID Emergency Department, indiscriminately, was performed. A routine lab analysis measured amino acids in plasma and urine of patients. Data of surviving and deceased patients and those requiring or not requiring mechanical ventilation were compared, and logistic regression analyses have been performed. Deceased patients were older, had higher blood glucose, potassium, AST, LDH, troponin, d-dimer, hsCRP, procalcitonin, interleukin-6 levels (p < 0.05 for all). They had lower plasma serine, glycine, threonine, tryptophan levels (p < 0.01), higher tyrosine and phenylalanine levels (p < 0.05), and higher fractional excretion of arginine, methionine, and proline (p < 0.05) than survivors. In a regression model, age, severity score of COVID-pneumonia, plasma levels of threonine and phenylalanine were predictors of in-hospital mortality. There was a difference in ventilated vs. non-ventilated patients in CT-scores, glucose, and renal function (p < 0.001). Using logistic regression, CT-score, troponin, plasma level, and fractional excretion of glycine were predictors of ventilation. Plasma levels and renal excretion of certain amino acids are associated with the outcome of COVID-19 infection beside other parameters such as the CT-score or age.

Chronic hemodialysis (HD) patients have very high cardiovascular risk. Acute vascular changes during dialysis mediated by factors of the endothelium may have a crucial role in this. Aim: To study acute vascular changes during HD. In 29 consecutive chronic HD patients (age: 65.6±10.4 years) pre-, mid-, and post-HD plasma syndecan-1 (SDC-1) and endothelin-1 (ET-1) levels were measured. Applanation tonometry was performed before HD. SDC-1 levels increased during HD (p=0.004). Males had higher ET-1 levels. Patients were divided into 2 groups based on pulse wave velocity (PWV): PWV≥12 m/s and PWV<12 m/s. Pre-HD and mid-HD SDC-1 levels were higher in the group with PWV≥12 m/s (10.174±2.568 vs. 7.928±1.794 ng/ml, p=0.013, and 10.319±3.482 vs. 8.248±1.793 ng/ml, p=0.044, respectively). Post-HD ET-1 levels were higher in the patient group having PWV≥12 m/s (10.88±3.00 vs. 8.05±3.48 pg/l, p=0.027). Patients having PWV≥12 m/s had higher pre-HD peripheral and aortic systolic blood pressure (p<0.05). Total cholesterol correlated with the SDC-1 decrease during HD (r=0.539; p=0.008). Pre-, mid-, and post-HD SDC-1 correlated with the ultrafiltration (r=0.432, p=0.019; r=0.377, p=0.044; and r=0.401, p=0.012, respectively). SDC-1 and ET-1 contribute to vascular changes observed during HD, and they have correlations with some cardiovascular risk factors.

Beyond their metabolic effect, SGLT-2 inhibitors reduce the risk of heart failure and have cardiovascular and nephroprotective effects, yet their exact mechanism of action remains unclear. This prospective study included 40 patients with type 2 diabetes whose physician initiated SGLT-2 inhibitor therapy. Prior to and after 4 weeks of the initiation of use of SGLT-2 inhibitors, in addition to routine clinical and laboratory measurements, hydroxyl free radical and neuropathic evaluations were performed. Body weight, BMI, fasting glucose, fructosamine, and albuminuria decreased significantly, whereas RBC count, hemoglobin, hematocrit, MCV, and platelet count increased significantly. Urinary o-tyrosine/p-tyrosine and (m-tyrosine+o-tyrosine)/p-tyrosine ratios were significantly reduced, suggesting diminished hydroxyl free radical production. Patients with neuropathy measured by the abnormal baseline CPT (current perception threshold) values showed significant improvements. Significant correlations between RBC, platelet parameters, albuminuria and hydroxyl free radical markers disappeared after SGLT-2-treatment, and changes of hydroxyl free radical markers correlated positively with CPT changes. Our results suggest that short-term SGLT-2 inhibition simultaneously recalibrates metabolic, hematologic, kidney and neuropathic endpoints, potentially through attenuating abnormal ortho- and meta-tyrosine incorporation into signaling proteins. Further studies are required to confirm long-term durability and examine whether additional strategies such as supplementation of the physiological p-tyrosine could amplify these benefits.