In a major study led by the Endocrinology and Diabetes team of the Faculty of Medicine at The Chinese University of Hong Kong (CU Medicine), and with collaborators from the University of Sydney and Western Sydney University, researchers have discovered that a unique DNA property can predict the decline of kidney function in diabetes patients over a 14 year follow-up period. The study was the largest, most detailed and included the longest follow-up period of its kind. The results have recently been published in the medical journal Diabetologia.

Type 2 diabetes is the leading cause of end-stage kidney disease

Diabetes, and type 2 diabetes in particular, is the leading cause of end-stage kidney disease and is highly prevalent in Asian populations. To advance timely clinical interventions, researchers around the world have devoted significant effort to discovering biomarkers which can identify individuals with type 2 diabetes at high risk of developing end-stage kidney disease or rapid decline in kidney function.

Telomere is the tail-end of DNA strands which contains a repeat code sequence that shortens with each cell division. Loss of these repeat sequences is associated with the shortening of telomere length, which indicates cellular aging. A large-scale cohort study published in 2020, conducted by the Endocrinology and Diabetes team at CU Medicine, proved that shortened DNA telomere length is a useful biomarker linked to a higher risk of developing cardiovascular disease in patients with type 2 diabetes.

Diabetes patients who develop end-stage kidney disease have shorter DNA telomere length

In this study, the team analysed the DNA data of 4,085 type 2 diabetes patients from the Hong Kong Diabetes Register, established in 1995. The research team measured the relative Leucocyte Telomere Length (rLTL) in DNA extracted from white blood cells (leucocytes) at baseline, and the subjects were followed-up over 14 years. 564 individuals developed incident end-stage kidney disease, while their baseline rLTL was shorter than the non-progressors.  The details are as follows:

Starting from mid-age and with a baseline value of around 100 mL/min, estimated glomerular filtration rate (eGFR), an indicator of kidney function, may decline by 1% every year in an average person due to aging. This rate of decline is doubled in an average patient with diabetes. A person is said to have end-stage kidney disease if the eGFR is lower than 15 mL/min, when dialysis may be needed.

In this study, researchers discovered that for each unit decrease in rLTL, the risk of the patients developing end-stage kidney disease was increased by 20%. This association remained significant, after adjusting for other factors such as age, sex and kidney function at baseline. Furthermore, shorter rLTL at baseline was associated with a rapid decline of eGFR of more than 4% every year, i.e., a loss of 40% of kidney function in 10 years.  

Professor Ronald Ching Wan MA, Head of the Division of Endocrinology and Diabetes (Academic Affairs), Department of Medicine and Therapeutics at CU Medicine, stated, “On top of traditional risk factors, our new findings supported the added value of DNA telomere length as a biomarker in identifying individuals with type 2 diabetes at high risk of end-stage kidney disease and rapid deterioration of kidney function for individualised and intensified treatment. Early intervention has been shown to delay the progression of kidney disease and prevent end-stage kidney disease in patients with diabetes.”

This research is the largest prospective study to comprehensively evaluate the relationship between baseline rLTL and the progression to end-stage kidney disease in individuals with type 2 diabetes.  The follow-up period of 14 years is also the longest among similar reports.

Professor Juliana Chung Ngor CHAN, Chair Professor of Medicine and Therapeutics and Founding Director of the Hong Kong Institute of Diabetes and Obesity at CUHK, added, “The high-quality database, biobank and research methods provided our study with robust statistical power to demonstrate the biological significance of DNA telomere length in predicting the risk of patients developing diabetes complications like kidney failure. Given the silent nature of diabetes, discovering biomarkers on top of conventional risk factors will increase the precision of risk prediction for personalised management which will assist in preventing hospitalisations, disabilities and premature death.”

This study is supported by the Research Grants Council Theme-based Research Scheme, the Research Impact Fund, and other funding support.