Science: Casting an eye on the vulnerable

At 14, Leonard Thompson’s life looked behind him. Weighing a mere 30 kilogrammes, he hovered on the brink of death. He had been starved in an attempt to cure him of his Type 1 diabetes. In a last-ditch attempt to save the boy’s life, his father agreed to allow doctors to inject Leonard, who by then was drifting in and out of a coma, with a newly discovered drug that had never been tested in humans. On Wednesday, January 11, 1922, Leonard received the injection. With that jab of the needle, he entered medical history as the first human to be injected with insulin.

Thanks to regular insulin injections, Leonard received a new lease of life and became a miracle of science. Unfortunately, he died 13 years later from pneumonia, a complication from diabetes. 

For centuries, history has shown that people like Leonard who live with comorbidities are more susceptible to other conditions and the novel coronavirus disease (Covid-19) seems to be no exception. 

“In Covid-19, emerging evidence shows an increased risk for severe disease and mortality in patients with diabetes, hypertension, hyperlipidaemia and obesity or metabolic syndrome. Age is also an independent predictor of severity,” said LKCMedicine Assistant Professor Rinkoo Dalan, who is also a Senior Consultant Endocrinologist at Tan Tock Seng Hospital. 

According to WHO data, eight out of 10 deaths occurred in individuals with at least one underlying co-morbidity, such as cardiovascular diseases/hypertension or diabetes. 

Even from the early days of the outbreak, diabetes was identified as a common condition in Covid-19 patients. Back in February, the Chinese Centre for Disease Control and Prevention published a case series of 72,314 Covid-19 infections in mainland China. The report found that close to 5,300 or more than seven per cent of those infected were diabetics. 

Therefore, anyone with diabetes, particularly those who are older, should pay extra attention to their health during this pandemic, said Asst Prof Dalan.  

Her thoughts were echoed by LKCMedicine Professor of Metabolic Medicine Bernhard Boehm who added that a diabetic who is 60 or older and infected with Covid-19, will likely face a worse clinical outcome.

Like the WHO, the International Diabetes Federation called on people with diabetes to take extra care during the Covid-19 pandemic. They are concerned because the immune system in people with diabetes is not as effective at controlling the spread of invading pathogens, such as viruses like Covid-19, bacteria and other microorganisms than in a person without the condition. That’s because the high blood sugar levels of a person with diabetes hamper the work of the immune system. 

Some factors such as excessive activation of neutrophils – a type of white blood cell – have shown to play a role in viral susceptibility and viral persistence in diabetic individuals, explained Asst Prof Dalan.

Diabetes is also a risk factor for hospitalisation and mortality from Covid-19 infection, said Prof Boehm. When infected, a diabetic’s already compromised immune system faces a much tougher fight, often leading to more severe disease and a longer recovery period. 

Between intensive care and non-intensive care patients with the coronavirus, Prof Boehm said there appears to be a twofold increase of patients in intensive care who have diabetes and threefold higher mortality risk in these individuals. 

Data released by the National Health Service for England in May revealed that one in four people who died in hospital with Covid-19 between 31 March and 12 May had either Type 1 or Type 2 diabetes. In Singapore, at least two of the 26 people who died from the coronavirus to date had a history of diabetes. 

“In addition, other components of the metabolic syndrome such as hypertension, increased blood lipid levels and the presence of cardiovascular complications also increase the risk of unfavourable clinical outcomes,” said Prof Boehm, who is also the Ong Tiong Tat Chair Professor in Diabetes Research.  

That’s because diabetes shares several risk factors with high blood pressure. The substantial overlap of both conditions causes problems in the heart and blood vessels. To reduce their risk of cardiovascular complications, many people with diabetes take drugs called ACE inhibitors. These drugs stop the angiotensin-converting enzyme 1 (ACE-1) from creating a peptide that causes the blood vessels to narrow and, thereby, increase blood pressure. But these drugs may also, inadvertently, make people with diabetes even more vulnerable to the virus.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human cells by sticking to a receptor called angiotensin-covering enzyme 2 (ACE-2). This receptor is on the surface of cells including those in the heart, kidney, stomach, intestines and lungs.

By stopping ACE-1 from doing its work, the ACE-1 inhibitors trigger cells to send more ACE-2 to the surface as a replacement. More such receptors on the cell surface make it easier for SARS-CoV-2 to stick to them. This makes it easier for the virus to enter the cell, leading to a more severe infection.

Nonetheless, LKCMedicine Nanyang Assistant Professor Christine Cheung, who is the Principal Investigator of the Laboratory of Molecular and Vascular Medicine, said the current recommendation is to closely monitor Covid-19 patients who are on ACE medications. That’s because ACE-2 has protective effects on the body, such as moderating inflammation and constriction of blood vessels.

“It is still a debate about the risk-benefit of withdrawing ACE drugs for diabetes. Rather, clinicians may look into better managing blood glucose level because hyperglycemia is known to promote virulence of some pathogens. In general, patients with pre-existing cardiovascular and diabetic conditions should be monitored very closely to prevent severe infections,” said Asst Prof Cheung.

Although diabetics are at higher risk of developing Covid-19 disease, LKCMedicine Assistant Professor of Metabolic Diseases Yusuf Ali said they can play their part by managing blood glucose levels well. 

“Poor blood sugar control not only makes management harder but also lowers your immune bar, thus increasing the risk of infection,” he added. 

Agreeing, Prof Boehm said the most important preventive element is an optimal, long-term control of blood sugar levels. “Since diabetes is a chronic disorder, the optimal glucose control has to (be) lifelong to reduce the risk of diabetes-associated complications and to mitigate the outcome of any kind of infectious diseases such as influenza or a bacterial pneumonia,” he added.