Sex Differences in Diabetic Cardiomyopathy and Treatment Response to AT-001
Bibliographic record
Abstract
BACKGROUND: Diabetic cardiomyopathy (DbCM) is a significant cause of heart failure (HF) in individuals with type 2 diabetes mellitus. Although sex differences are noted in HF patients, it is unclear if such differences exist in those with DbCM and whether sex-based differences affect treatment responses. OBJECTIVES: This analysis focuses on sex differences in baseline characteristics of study participants with DbCM at high risk for progression to overt HF and sex-based treatment responses to high-dose AT-001, a novel aldose reductase inhibitor. METHODS: The ARISE-HF trial was a Phase 3, randomized, international, placebo-controlled study designed to evaluate the efficacy and safety of AT-001 in study participants with DbCM. RESULTS: Of 691 participants, 348 (50.4%) were women. At baseline, women had higher N-terminal pro-B-type natriuretic peptide concentrations (92 vs 60 ng/L; P < 0.001), lower peak oxygen uptake (13.87 vs 17.59 mL/kg/min; P < 0.001), shorter cardiopulmonary exercise testing durations (8.47 vs 11.05 minutes; P < 0.001), and worse quality of life and health status (Kansas City Cardiomyopathy Questionnaire overall summary score 87.79 vs 92.55; P < 0.001; Physical Activity Scale for the Elderly score 137.87 vs 171.09; P < 0.001) compared with men. Despite these differences, there were no significant sex differences in the efficacy or tolerability of high-dose AT-001 compared with placebo. The placebo-corrected oxygen uptake change was 0.26 for women and 0.27 for men (P = 0.58), and changes from baseline to month 15 in Kansas City Cardiomyopathy Questionnaire and Physical Activity Scale for the Elderly scores showed no significant sex differences (all P > 0.05). CONCLUSIONS: Despite baseline differences between women and men with DbCM, the efficacy and safety of high-dose AT-001 are comparable across sexes. These findings highlight the presence of sex-specific characteristics in DbCM and underscore the importance of further research to understand potential sex-specific mechanisms. (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial [ARISE-HF]; NCT04083339).
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How this classification was reachedexpand
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".