DNA telomere length linked to diabetes cardiovascular risk

20 August 2020

A large cohort study, led by Professor Ronald Ching Wan Ma (Croucher Senior Medical Research Fellowship 2020, Croucher Fellowship 2001), at The Chinese University of Hong Kong (CUHK), together with the University of Sydney, Australia, has revealed a useful new biomarker for identifying type 2 diabetes patients at high risk of developing cardiovascular disease.

The team’s 13-year study has identified shortened DNA telomere length to be a valuable indicator of future cardiovascular disease in patients with type 2 diabetes. Telomeres, located at both ends of DNA strands, contain a repeat code sequence that shortens with each cell division. Loss of these repeat sequences is associated with shortening of telomere length, which indicates cellular ageing.

To evaluate the role of shortened DNA telomere length in their research, the Endocrinology and Diabetes team, headed by Ma, studied the data of 5,349 patients with type 2 diabetes from the Hong Kong Diabetes Register, established in 1995.

During the 13-year follow-up period, the team discovered that patients with cardiovascular disease at the baseline of the study or during follow-up had shorter telomeres, expressed as relative Leukocyte Telomere Length (rLTL), than those who never had cardiovascular disease. For each unit relative decrease in rLTL, the risk of cardiovascular disease increased by 25 per cent.

Patients with diabetes have two to four times increased risk of cardiovascular disease than those without diabetes. CUHK medical researchers reported that 15 per cent of type 2 diabetes patients attending Hospital Authority clinics were found, during assessment, to have had a prior history of cardiovascular disease, with another 15 per cent developing cardiovascular disease after an average of 6.7 years of follow-up.

“Our study demonstrated shortened rLTL was not only associated with a past history of cardiovascular disease, but also independently predicted the future risk of developing cardiovascular disease,” said Ma, who is Head of the Division of Endocrinology and Diabetes in the Department of Medicine and Therapeutics in the Faculty of Medicine, CUHK. “This makes rLTL a useful biomarker for identifying individuals with type 2 diabetes who are at high risk of developing cardiovascular disease for intensive control of other modifiable risk factors.”

These results have been published in the leading diabetes journal, Diabetes Care.

Ma was the project coordinator for a five-year Theme-based Research Scheme grant awarded in 2013/14 for a multidisciplinary project to identify genetic and epigenetic markers for diabetic complications, and to establish a multi-centre prospective cohort and biobank of patients with type 2 diabetes. The project received HK$60 million from the Hong Kong Research Grants Council under the scheme.

In 2019, Ma was awarded a Croucher Senior Medical Research Fellowship, commencing in 2020, to continue his research. This includes the development of clinical tools, such as polygenic risk scores, for predicting diabetes complications and outcomes. The team is now conducting further studies to validate the use of rLTL as a biomarker to predict other diabetes complications, such as kidney disease, which are the leading causes of hospitalisations, disabilities and premature death worldwide.

Professor Ronald Ching Wan Ma is Head of the Division of Endocrinology and Diabetes, Department of Medicine and Therapeutics, Chinese University of Hong Kong. He completed his medical training at the University of Cambridge, UK, and trained in internal medicine in London. Following endocrine fellowship training in Hong Kong, he was awarded a Croucher Fellowship in 2001 to further his research interest in diabetic complications at the Joslin Diabetes Center, Harvard Medical School. He joined the Chinese University of Hong Kong in 2008 and in 2013 his group was the first to identify a genetic variant near the PAX4 gene as a novel predictor of type 2 diabetes in Chinese and other Asian populations. He received a Croucher Senior Medical Research Fellowship in 2020.

To view Professor Ma’s Croucher profile, please click here.