SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients
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Bibliographic record
Abstract
Background: Frailty is a multidimensional condition often diagnosed in older adults with hypertension and diabetes, and both these conditions are associated with endothelial dysfunction and oxidative stress. We investigated the functional role of the SGLT2 (sodium glucose cotransporter 2) inhibitor empagliflozin in frail diabetic and hypertensive older adults. Methods: We studied the effects of empagliflozin in consecutive hypertensive and diabetic older patients with frailty presenting at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, from March 2021 to January 2022. Moreover, we performed in vitro experiments in human endothelial cells to measure cell viability, permeability, mitochondrial Ca 2+ , and oxidative stress. Results: We evaluated 407 patients; 325 frail elders with diabetes successfully completed the study. We propensity-score matched 75 patients treated with empagliflozin and 75 with no empagliflozin. We observed a correlation between glycemia and Montreal Cognitive Assessment (MoCA) score and between glycemia and 5-meter gait speed (5mGS). At 3-month follow-up, we detected a significant improvement in the MoCA score and in the 5mGS in patients receiving empagliflozin compared with non-treated subjects. Mechanistically, we demonstrate that empagliflozin significantly reduces mitochondrial Ca 2+ overload and reactive oxygen species production triggered by high glucose in human endothelial cells, attenuates cellular permeability, and improves cell viability in response to oxidative stress. Conclusions: Taken together, our data indicate that empagliflozin reduces frailty in diabetic and hypertensive patients, most likely by decreasing the mitochondrial generation of reactive oxygen species in endothelial cells.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it