Heart failure in type 2 diabetes: improving diagnosis and management in a multi-ethnic population.

Research question: Can we improve the detection, prevention and treatment of heart failure (HF) in type 2 diabetes (T2D)? Background: In 2015/16, one third of hospital admissions for HF were in people with diabetes (>115,000) despite representing only 6% of the population. The epidemic of obesity in children and T2D in younger adults, who have the highest lifetime risk, represents a potential time-bomb of patients who will develop HF. Early HF (before symptoms develop) can be detected with cardiac imaging, providing a potential therapeutic target but the causes and treatment are not well understood, especially in ethnic minorities and females. Aims: to improve the management of HF in T2D. Specific objectives in the work packages (WP) are to determine in T2D: WP1- How common early HF is (imaging) in a multi-ethnic population and to devise a clinical risk score to identify those with HF. WP2 -Develop a blood test(s) that can accurately diagnose patients with early HF. WP3- Whether treatment with an SGLT2i or intensive blood pressure lowering can reverse early HF in younger adults ( WP4- Whether a low-calorie diet is a feasible treatment in a multi-ethnic cohort of obese patients with HFpEF. Methods: In all WP, patients will be extensively phenotyped with glcyometabolic profiling, 24 hour blood pressure, echocardiography and cardiac MRI. WP1: cross sectional study of 600 adults with T2D and no established cardiovascular disease from a multi-ethnic population in Leicestershire. Independent risk factors for early HF will be determined and a clinical risk score will be devised. WP2- using detailed proteomic analyses in 50 patients from WP1 we will develop a panel of blood biomarkers that accurately identifies early HF (discovery set). This will be internally validated in the remaining cohort and externally validated in a subset of the UK Biobank population. WP3- prospective, randomised, open label, multicentre, blinded endpoint trial in 825 adults ( WP4 is a feasibility study of a 12 week low-calorie meal replacement diet aiming to recruit 20 obese adults with T2D and HF with preserved ejection fraction, which has no proven treatments. Outcomes: recruitment, compliance, symptoms, cardiac imaging. Timelines for delivery- Start November 2018. Completion: WP1 and 2: 2022; WP4 2019 and if successful further funding will be sought (2020). Funding for WP3 will be applied for aiming to start in 2019 and complete in 2023. Anticipated impact and dissemination: The results will impact on the management of HF in T2D globally. Dissemination will be through traditional scientific conferences, journal articles and conventional and new media with support from patient representatives, NIHR communications team and charities.