• Among Asian patients with heart failure, lean-fat patients with large waists despite low body mass index (BMI), face higher rates of hospitalisation and death.
  • National Heart Centre Singapore researchers together with Asia-wide investigators are embarking on a multinational clinical trial to help prevent heart diseases in high-risk patients with diabetes.

Singapore, 28 August 2020
– A team of researchers from the National Heart Centre Singapore (NHCS) has identified for the first time a unique lean diabetic phenotype among Asian patients with heart failure, and discovered that Asian patients with heart failure had a high prevalence of diabetes despite having low BMI.

Led by Professor Carolyn Lam, Senior Consultant from the Department of Cardiology, NHCS and Professor of Cardiovascular Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, the team found that these lean diabetic patients were at high risk of hospitalisation and death, and these patients with large waist-to-height ratios, even when BMI was low were at the highest risk of poor outcomes. These landmark findings were published in several high impact scientific journals1.

Conventionally, diabetes is associated with obesity, defined by BMI, resulting in hyperinsulinemia, glucose intolerance and insulin resistance – a phenotype largely described in Western populations. However, in a cross-sectional comparison of Asian and Caucasians with heart failure, Asians patients had threefold higher prevalence of diabetes, despite lower BMI. “When we systematically examined comorbidities among Asian patients with heart failure, we identified a unique lean diabetic heart failure phenotype in Asia. The lean diabetic cluster was associated with the worst quality of life and composite outcomes, with 79% greater risk of hospitalisation and mortality at one year, compared with other clusters,” said Dr Chanchal Chandramouli, Research Fellow, NHCS who specialises in research on cardiometabolic disorders and heart failure.

Diabetes mellitus is not only a lifelong disease of epidemic proportions in Singapore and across Asia, but also a major cause of heart disease, stroke, hospitalisation and death. The number of adults in Singapore with diabetes is projected to increase from 440,000 to one million within 30 years, and this has called for the nation to declare ‘war on diabetes’ in 2016. Diabetes accelerates the development of heart disease, by as much as 14 years earlier onset, compared to those without diabetes. Correspondingly, heart or blood vessel disease is the leading cause of death among diabetic patients. According to the National Registry of Diseases Singapore, one in two people with a heart attack and two in five people with stroke had co-existing diabetes.

Launch of Trial to Prevent Heart Disease in Diabetics

“Realising the dismal prognosis of lean diabetic patients with heart failure and the lack of proven therapies to improve their prognosis, our team firmly believes that prevention of future cardiac disease among high-risk diabetic asymptomatic individuals is extremely critical,” said Professor Carolyn Lam.

Along with a panel of investigators Asia-wide, NHCS researchers are now embarking on a multinational prospective study – Asian Diabetes Outcome Prevention Trial (ADOPT). ADOPT aims to strategically identify diabetic individuals with high-risk of heart disease and prioritise them for intensive preventive treatment. Using blood biomarker-based screening and intensive preventive strategy, this trial is designed to test if a specific strategy of treatment might reduce the onset of heart disease including stroke among high risk individuals with diabetes, compared to standard care.

“If ADOPT proves that a simple blood test can identify individuals with diabetes who will benefit from intensive preventive therapy with commonly available medications, results can directly impact clinical practice not only in Singapore, but in other parts of the world,” said Professor Carolyn Lam, who is also the Principal Investigator of ADOPT, and a member of the Research EXCO in the SingHealth Duke-NUS Cardiovascular Sciences Academic Clinical Programme.

“Among patients with diabetes in Singapore, about 20 per cent have normal BMI. Adding to that is the worrisome finding of a lean diabetic heart failure phenotype which potentially could lead to reduced quality of life, disability, hospitalisation, and poor health outcomes. Early detection of high-risk patients for targeted intervention will be key to reducing this complication,” said Clinical Associate Professor Bee Yong Mong, Senior Consultant from Department of Endocrinology at Singapore General Hospital (SGH), and the country head of ADOPT in Singapore.

“In Singapore, the cost of diabetes is expected to soar to S$2.5 billion by 2050, given the current standard of care. Managing cardiovascular complications substantially adds to the direct costs of treating diabetes. This is a tremendous burden to healthcare systems across Asia. If proven effective, this treatment regime could also potentially help save diabetes-associated healthcare cost in Singapore and beyond,” said Dr Chanchal Chandramouli who is a key co-investigator and Steering Committee Member of ADOPT.

The ADOPT study will be conducted in 30 centres across six Asian regions including Singapore, Malaysia, China, Taiwan, India and United Arab Emirates. The team aims to recruit 2,400 volunteers with follow-up over a duration of four years. “We are thrilled to share that our partner and one of the ADOPT sites in Singapore – Changi General Hospital has recruited our first patient worldwide on 27 August 2020. This signifies a remarkable start and a major milestone for the trial,” said Professor Carolyn Lam.

This investigator-initiated trial received support from the National Medical Research Council of Singapore, philanthropic and commercial partners.

  • Chandramouli C, Tay WT, Bamadhaj NS, et al. Association of obesity with heart failure outcomes in 11 Asian regions: A cohort study. PLoS Med. 2019;16(9):e1002916. Published 2019 Sep 24. doi:10.1371/journal.pmed.1002916
  • Yap J, Tay W, Teng T, Anand I, Richards A, Ling L, MacDonald M, Chandramouli C, Tromp J, Siswanto B, Zile M, McMurray J, Lam C. Association of Diabetes on Cardiac Remodeling, Quality of Life and Clinical Outcomes in Heart Failure with Reduced and Preserved Ejection Fraction. J Am Heart Assoc. Aug 2019; In-press.
  • Cooper LB, Yap J, Tay WT, Teng TK, MacDonald M, Anand IS, Sharma A, O'Connor CM, Kraus WE, Mentz RJ, Lam CS, Hf A, Investigators A-H. Multi-ethnic comparisons of diabetes in heart failure with reduced ejection fraction: insights from the HF-ACTION trial and the ASIAN-HF registry. Eur J Heart Fail. 2018; doi:10.1002/ejhf.1223.
  • Tromp J, Tay WT, Ouwerkerk W, et al. Multimorbidity in patients with heart failure from 11 Asian regions: A prospective cohort study using the ASIAN-HF registry [published correction appears in PLoS Med. 2018 May 25;15(5):e1002583]. PLoS Med. 2018;15(3):e1002541. Published 2018 Mar 27. doi:10.1371/journal.pmed.1002541
  • Bank IEM, Gijsberts CM, Teng TK, et al. Prevalence and Clinical Significance of Diabetes in Asian Versus White Patients With Heart Failure. JACC Heart Fail. 2017;5(1):14-24. doi:10.1016/j.jchf.2016.09.015