Abstract
Objective: People with T2D have increased risk of heart failure, with fibro-inflammatory pathways implicated in the pathogenesis. This secondary analysis assessed the relationship between multiple fibro-inflammatory biomarkers and cardiovascular (CV) structure and function in patients with T2D and asymptomatic nondiabetic controls and the impact of two lifestyle interventions, exercise training or meal replacement plan (MRP). Methods: Data was derived from a randomised controlled trial (RCT), including a nested case-control study. Adults with T2D and no CV disease were randomized (1:1:1) to a 12-week intervention of 1) supervised aerobic exercise training, 2) a low-energy (∼810 kcal/day) MRP or 3) standard care. Fasting bloods for fibro-inflammatory biomarkers and cardiac MRI (CMR) were undertaken pre- and post-intervention. Principal component analysis (PCA) was performed to visualise this multivariate dataset in a 3D space to understand the relationship between CMR outcomes of interest (e.g., cardiac geometry, systolic and diastolic function), key demographic variables (age, sex, ethnicity and smoking status) and the fibro-inflammatory biomarkers (total of 68 variables) between cases and controls and pre-post intervention. Results: At baseline 36 controls and 83 T2D were compared of which 76 participants completed the RCT. People with T2D had an adverse fibro-inflammatory profile compared to controls’. The PCA 3D-visulisation containing demographics, biomarkers and CMR data shows almost complete separation between controls and those with T2D. Following MRP there was a marked shift in the PCA but not for the exercise intervention. Conclusion: Alterations in fibro-inflammatory pathways impact CV structure and function before the onset of symptomatic heart failure in people with T2D. The MRP improved this fibro-inflammatory profile but not exercise. Longer term studies are required to determine whether the MRP can reduce symptomatic heart failure. Disclosure E. M. Brady: Other Relationship; Self; Bristol Myers Squibb Pharmaceutical company. E. Mirkes: None. K. Parke: None. G. S. Gulsin: None. L. Athithan: None. J. Henson: None. T. Yates: None. M. J. Davies: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi, Other Relationship; Self; AstraZeneca, NIHR Leicester Biomedical Research Centre, Novo Nordisk, Speaker's Bureau; Self; Astra Zeneca Pharma India Ltd, Boehringer Ingelheim (China), Boehringer Ingelheim (Philippines), Inc., Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Boehringer Ingelheim Saudi Arabia Trading, Boehringer Ingelheim Singapore Pte. Ltd, Boehringer Ingelheim Sp. Z o. o., Eli Lilly and Company, Napp Pharmaceuticals, Novo Nordisk, Novo Nordisk A/S, S. C. Sanofi Romania SRL, Sanofi K. K. G. P. Mccann: None. P. Kanagala: None. L. Ng: None. Funding National Institute for Health Research (CDF2014-07-045 to G.P.M.)
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