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BMI variability and cardiovascular outcomes within clinical trial and real-world environments in type 2 diabetes: an IMI2 SOPHIA study

Abstract:
Background
BMI variability has been associated with increased cardiovascular disease risk in individuals with type 2 diabetes, however comparison between clinical studies and real-world observational evidence has been lacking. Furthermore, it is not known whether BMI variability has an effect independent of HbA1c variability.
Methods
We investigated the association between BMI variability and 3P-MACE risk in the Harmony Outcomes trial (n = 9198), and further analysed placebo arms of REWIND (n = 4440) and EMPA-REG OUTCOME (n = 2333) trials, followed by real-world data from the Tayside Bioresource (n = 6980) using Cox regression modelling. BMI variability was determined using average successive variability (ASV), with first major adverse cardiovascular event of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death (3P-MACE) as the primary outcome.
Results
After adjusting for cardiovascular risk factors, a + 1 SD increase in BMI variability was associated with increased 3P-MACE risk in Harmony Outcomes (HR 1.12, 95% CI 1.08–1.17, P < 0.001). The most variable quartile of participants experienced an 87% higher risk of 3P-MACE (P < 0.001) relative to the least variable. Similar associations were found in REWIND and Tayside Bioresource. Further analyses in the EMPA-REG OUTCOME trial did not replicate this association. BMI variability’s impact on 3P-MACE risk was independent of HbA1c variability.
Conclusions
In individuals with type 2 diabetes, increased BMI variability was found to be an independent risk factor for 3P-MACE across cardiovascular outcome trials and real-world datasets. Future research should attempt to establish a causal relationship between BMI variability and cardiovascular outcomes.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1186/s12933-024-02299-8

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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
NDM Experimental Medicine
Role:
Author
ORCID:
0009-0009-3138-6798


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Funder identifier:
https://ror.org/00k4n6c32
Programme:
Horizon 2020 research and innovation program


Publisher:
BioMed Central
Journal:
Cardiovascular Diabetology More from this journal
Volume:
23
Issue:
1
Article number:
256
Place of publication:
England
Publication date:
2024-07-16
Acceptance date:
2024-06-10
DOI:
EISSN:
1475-2840
Pmid:
39014446


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