The HKUMed team conducted a thorough examination of 40 blood samples from T2D patients at Queen Mary Hospital, which revealed a notable 40% decrease in functionality of Th1 cells derived from PC-T2D patients. The research involved further animal experimentation to identify the mechanistic link. (From left) Professor Kathryn Tan Choon-beng, Professor Heidi Ling Guangsheng, T2D patient Mr Kwok, and Dr Paul Lee Chi-ho.
A research team from the LKS Faculty of Medicine of the University of Hong Kong (HKUMed) has identified a mechanistic link between high blood glucose levels and weakened immunity against viral infections in patients with type 2 diabetes (T2D). The collaborative research highlights the increased susceptibility of T2D patients to more frequent and severe viral infections, emphasising the importance of maintaining optimal blood glucose levels as a vital public health measure. The research findings, published in Cell Metabolism (link to publication), provide valuable insights into the mechanisms underlying these health risks.
Background
In Hong Kong, T2D is a substantial public health concern, affecting about 1 in 10 adults. Despite the advances in pharmacotherapy in managing T2D, a significant number of patients still struggle to achieve optimal glycaemic control. Notably, patients with poorly controlled T2D (PC-T2D) are particularly vulnerable, experiencing more frequent and severe health risks.
The human body usually has a strong defence against viral infections, primarily through the rapid production of anti-viral T cells. Specifically, when a virus is detected, T Helper 1 (Th1) cells are generated to facilitate an inflammatory response needed to eradicate infected cells. However, during the recent COVID-19 pandemic, it was observed that COVID-19 patients with T2D had a mortality risk three times higher than those without T2D, and the majority of fatalities among T2D patients occurred in those with poorly controlled diabetes.
The HKUMed research team conducted a study to discover the reasons behind this heightened vulnerability and to explore strategies to improve outcomes for T2D patients.
Research findings
Led by Professor Heidi Ling Guangsheng from the School of Biomedical Sciences, and Dr Paul Lee Chi-Ho and Professor Kathryn Tan Choon-Beng from the Department of Medicine, School of Clinical Medicine, HKUMed, the research team discovered how elevated blood glucose levels in patients with PC-T2D resulted in worse anti-viral responses. The team conducted a thorough examination of 40 blood samples from T2D patients at Queen Mary Hospital from 2022 to 2023, which revealed a notable 40% decrease in functionality of Th1 cells derived from PC-T2D patients, compared to those from healthy individuals. Fortunately, Th1 functionality was reinstated in patients with well-controlled blood glucose levels (WC-T2D), underscoring the importance of effective glycaemic control in bolstering anti-viral immunity.
Further experimentation using immune cell cultures and animal models demonstrated that elevated blood glucose levels impaired the metabolism in CD4+T cells. This leads to the degradation of a key transcription factor needed for their development into functional Th1 cells, diminishing their ability to respond effectively to viruses and other pathogens. Moreover, this impairment may trigger a chronic inflammatory response, further compromising the immune system and increasing the risk of various health issues.
Research significance
The research team found that T2D patients with better glycaemic control do not experience the harmful effects of T cell dysfunction, emphasising the importance of regular medication and strict adherence to treatment plans. By identifying the mechanisms of high glucose-mediated CD4+T cell dysfunction, this study opens avenues for new treatment options to improve the immunity of patients with T2D.
'These research findings stress the importance of keeping blood glucose levels under control. A strong immune system is crucial for alleviating the healthcare burden during viral pandemics and for protecting lives,' remarked Professor Heidi Ling Guangsheng, one of the corresponding authors of the study.
'These findings are particularly relevant for T2D patients, who are at a greater risk of experiencing severe symptoms from COVID-19 and have heightened susceptibility to influenza and other respiratory infections,' stated Dr Paul Lee Chi-ho, also a corresponding author. 'It is essential for T2D patients to understand more their glycaemic control, learn about their glycated haemoglobin (HbA1c) levels, adhere to their medication regimen and maintain a healthy lifestyle. These measures are the most effective ways to control blood sugar levels and protect against deadly co-morbidities and infections.'
About the research team
The study was jointly conducted by researchers from HKUMed: Professor Heidi Ling Guangsheng, Assistant Professor, School of Biomedical Sciences; Dr Paul Lee Chi-ho, Clinical Associate Professor, and Professor Kathryn Tan Choon-beng, both from the Department of Medicine, School of Clinical Medicine. Victor Gray and Chen Weixin, PhD students in the School of Biomedical Sciences, HKUMed, were co-first authors.
Acknowledgements
The research was supported by the General Research Fund of the Research Grants Council and the Health and Medical Research Fund.
