P1267Empagliflozin prevention of heart failure development in diabetes is associated with an improvement in cardiac energy producition
Bibliographic record
Abstract
Background: Empagliflozin treatment of diabetic patients at risk for cardiovascular disease results in a significant decrease in the risk of heart failure development and mortality. In this study, we determined whether empagliflozin's cardiovascular benefits are associated with an improvement in cardiac energy production. Methods and results: 18 week-old db/db mice were treated with empagliflozin or vehicle for 4 weeks (10/mg/kg/day via their food). Empagliflozin treatment prevented the development of heart failure in the db/db mice (cardiac work in isolated working hearts was 1.37±0.14 joules min–1 g dry wt–1, compared to 0.84±0.08 in vehicle-treated db/db mice (p<0.05), and 1.49±0.12 in non-diabetic control mice). The rates of glucose, fatty acid and ketone oxidation were measured in isolated working hearts perfused with 5 mM glucose, 0.8 mM palmitate, 0.6 mM β-hydroxybutyrate (β-OHB), and 500 μU/ml insulin. In db/db vehicle-treated mice, glucose oxidation rates were decreased by 61%, compared to control mice, but only by 43% in empagliflozin-treated diabetic mice. Interestingly, cardiac ketone oxidation rates in db/db mice decreased to 45% of the rates seen in control mice, while a similar decrease (43%) was seen in empagliflozin-treated db/db mice. Overall cardiac ATP production rates decreased by 36% in db/db vehicle-treated hearts compared to control mice, with fatty acid oxidation providing 42%, glucose oxidation 26%, ketone oxidation 10%, and glycolysis 22% of energy production. In empagliflozin-treated db/db mice, cardiac ATP production rates increased by 31% compared to db/db vehicle-treated mice, primarily due to a 42% increase in the contribution of glucose oxidation to energy production. Cardiac efficiency (cardiac work/O2 consumed) decreased by 28% in db/db vehicle-treated hearts compared to control hearts. Empagliflozin treatment of db/db mice did not increase cardiac efficiency. Since empagliflozin treatment increases circulating ketones in diabetics, we also determined what effect adding 600 μM β-OHB to db/db mouse hearts has on cardiac efficiency compared to db/db hearts perfused without ketones. The addition of 600 μM β-OHB, while not affecting glucose or fatty acid oxidation rates, resulted in ketone oxidation rates of 408±26 nmol min–1 g dry wt–1. This was accompanied by a 14.6% increase in ATP production compared to db/db hearts perfused without ketones, signifying the additional contribution of ketone oxidation to energy production.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".