BMI Variability and Cardiovascular Outcomes Within Clinical Trial and Real-World Environments in Type 2 Diabetes: An IMI2 SOPHIA study
Copyright policy )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.
- Queen Mary University of London United Kingdom
- Boehringer Ingelheim (Germany) Germany
- Boehringer Ingelheim Fonds Germany
- Institute of Population Health Canada
- Eli Lilly and Company Limited United Kingdom
Male, Blood Glucose, Time Factors, 610, /dk/atira/pure/subjectarea/asjc/2700/2705, name=Internal Medicine, Risk Assessment, Body Mass Index, BMI variability, Risk Factors, /dk/atira/pure/subjectarea/asjc/2700/2724, Diseases of the circulatory (Cardiovascular) system, Humans, Diabetes management ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use [MeSH] ; Type 2 diabetes ; Aged [MeSH] ; Risk Assessment [MeSH] ; Cardiovascular disease ; Cardiovascular Diseases/diagnosis [MeSH] ; Risk Factors [MeSH] ; Diabetes Mellitus, Type 2/mortality [MeSH] ; Randomized Controlled Trials as Topic [MeSH] ; 3P-MACE risk ; HbA1c variability ; Heart Disease Risk Factors [MeSH] ; Male [MeSH] ; Health outcomes ; Cardiovascular Diseases/mortality [MeSH] ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects [MeSH] ; Diabetes Mellitus, Type 2/diagnosis [MeSH] ; BMI variability ; Female [MeSH] ; Diabetes Mellitus, Type 2/complications [MeSH] ; Biomarkers/blood [MeSH] ; Humans [MeSH] ; Treatment Outcome [MeSH] ; Cardiovascular Diseases/epidemiology [MeSH] ; Middle Aged [MeSH] ; Diabetes Mellitus, Type 2/blood [MeSH] ; Time Factors [MeSH] ; Body Mass Index [MeSH] ; Glycated Hemoglobin/metabolism [MeSH] ; Research ; Blood Glucose/metabolism [MeSH] ; Blood Glucose/drug effects [MeSH], Sodium-Glucose Transporter 2 Inhibitors, Aged, Randomized Controlled Trials as Topic, Glycated Hemoglobin, 3P-MACE risk, HbA1c variability, Research, Type 2 diabetes, Health outcomes, Middle Aged, Cardiovascular disease, Diabetes and Metabolism, Diabetes management, Treatment Outcome, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Heart Disease Risk Factors, /dk/atira/pure/subjectarea/asjc/2700/2712, RC666-701, Female, name=Endocrinology, Biomarkers, name=Cardiology and Cardiovascular Medicine
Male, Blood Glucose, Time Factors, 610, /dk/atira/pure/subjectarea/asjc/2700/2705, name=Internal Medicine, Risk Assessment, Body Mass Index, BMI variability, Risk Factors, /dk/atira/pure/subjectarea/asjc/2700/2724, Diseases of the circulatory (Cardiovascular) system, Humans, Diabetes management ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use [MeSH] ; Type 2 diabetes ; Aged [MeSH] ; Risk Assessment [MeSH] ; Cardiovascular disease ; Cardiovascular Diseases/diagnosis [MeSH] ; Risk Factors [MeSH] ; Diabetes Mellitus, Type 2/mortality [MeSH] ; Randomized Controlled Trials as Topic [MeSH] ; 3P-MACE risk ; HbA1c variability ; Heart Disease Risk Factors [MeSH] ; Male [MeSH] ; Health outcomes ; Cardiovascular Diseases/mortality [MeSH] ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects [MeSH] ; Diabetes Mellitus, Type 2/diagnosis [MeSH] ; BMI variability ; Female [MeSH] ; Diabetes Mellitus, Type 2/complications [MeSH] ; Biomarkers/blood [MeSH] ; Humans [MeSH] ; Treatment Outcome [MeSH] ; Cardiovascular Diseases/epidemiology [MeSH] ; Middle Aged [MeSH] ; Diabetes Mellitus, Type 2/blood [MeSH] ; Time Factors [MeSH] ; Body Mass Index [MeSH] ; Glycated Hemoglobin/metabolism [MeSH] ; Research ; Blood Glucose/metabolism [MeSH] ; Blood Glucose/drug effects [MeSH], Sodium-Glucose Transporter 2 Inhibitors, Aged, Randomized Controlled Trials as Topic, Glycated Hemoglobin, 3P-MACE risk, HbA1c variability, Research, Type 2 diabetes, Health outcomes, Middle Aged, Cardiovascular disease, Diabetes and Metabolism, Diabetes management, Treatment Outcome, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Heart Disease Risk Factors, /dk/atira/pure/subjectarea/asjc/2700/2712, RC666-701, Female, name=Endocrinology, Biomarkers, name=Cardiology and Cardiovascular Medicine
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