Associations between Allopurinol and Cardiovascular and Renal Outcomes in Diabetes
Bibliographic record
Abstract
Diabetes is a leading cause of cardiovascular and kidney disease, and novel therapies to reduce these adverse diabetes outcomes are urgently required. Allopurinol, a uric acid-lowering therapy traditionally used for the treatment of gout, may reduce mortality and cardiovascular and kidney disease through reductions in oxidative stress and improved endothelial function, but this has not been well-studied in diabetes. Through three related projects, this thesis examines the associations between allopurinol and all-cause mortality, cardiovascular and renal outcomes in individuals with diabetes using population-based administrative health care data in Ontario, Canada. The first project examined patterns of allopurinol use and their predictors, to inform the design of subsequent studies. In 38,416 individuals with diabetes newly prescribed allopurinol, discontinuation and interruption of allopurinol were common. Female sex and greater severity of gout were associated with worse adherence. The second project evaluated the association between allopurinol-exposed time and all-cause mortality and cardiovascular outcomes in 38,416 new allopurinol users with diabetes. Allopurinol-exposed time was associated with a reduced risk of the primary composite outcome of all-cause mortality, atherothrombotic cardiovascular events (myocardial infarction, revascularization, stroke), or heart failure, which was primarily driven by a reduction in all-cause mortality. However, healthy user bias could not be completely excluded. The third project evaluated the association between allopurinol use and progression of chronic kidney disease (CKD) or development of end-stage renal disease (ESRD). In 5937 individuals with a gout flare and Stages 1 to 3 CKD at baseline (1911 with diabetes), renal outcomes did not differ between allopurinol users and non-users after weighting by the inverse probability of treatment. Based on the thesis results, allopurinol may reduce mortality and atherothrombotic cardiovascular events in individuals with diabetes, but does not appear to reduce heart failure, CKD progression, or development of ESRD. Defining allopurinol exposure in pharmacoepidemiology studies is challenging due to frequent interruptions and discontinuation. Thus, study designs incorporating time-varying exposure and time-varying confounders may be more robust. A clinical trial designed to evaluate the effect of allopurinol on atherothrombotic cardiovascular events in individuals with diabetes and hyperuricemia is strongly justified.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".