Glycemic Variability holds the key to diabetic complications

A FORTNIGHT ago, I wrote about my Apple watch that was a birthday present from my better half. We foresaw that the Apple watch would eventually be a telemetry device for human beings. One of the interesting upcoming developments by Apple is the ability to measure sugar non-invasively.

So what is it about sugar? In the ’60s and ’70s we demonised fat as the cause of heart attacks and strokes. From the last decade, we realised that in substituting sugar in the place of fats, we had inadvertently triggered an avalanche of obesity, diabetes and chronic diseases.

The pendulum had swung so much that major food companies globally had pushed the presence of sugar and corn syrup in processed foods, low fat products and fast foods. As the global population consumed more refined sugars, the propen-sity to have the sugar rush and the yearning for more sugar had triggered the medical equivalent of horsemen of the apocalypse.

So really, what is it about sugar? We know that there are ways to measure foods and their sugar content. The first is the Glycemic Index or GI. This essentially measures how fast the food turns to sugar in our gut and is absorbed into the blood stream. We assign a perfect score of 100 to a glass of sugar syrup. White rice is about 73, white bread is 75 while potato is in the 80s. Pasta, glass noodles, soba, udon and rolled oats are a lot better weighing in at the 50 range. You are obviously better off eating low GI foods.

The third term we should know about sugar is Glycemic Response or GR. This is essentially the beautiful peaks and troughs of our sugar levels related to our mealtimes. We found from the analytics that the peaks can be measured statistically in many ways. We can measure how fast the sugar peaks after a meal over time, we can measure the area under the curve of the peak, we can measure how fast the sugar drops from the peak over time and we can also measure the troughs. The troughs are interesting as some of the subjects have very low blood sugars after a huge peak. They are on the verge of hypoglycemia but have no symptoms or have no recollection, as they are fast asleep.

We know that there is something called “reactive hypoglycemia”. This is when one takes a big meal of high GI carbohydrates and there is a flood of insulin released. The insulin clears the sugar from the bloodstream but due to reasons unknown, the insulin surge and its after-effects seem to carry on to push the blood sugar to very low levels.

What is the point of measuring all these intricacies of the peaks and troughs of blood sugar? We then come to the fourth and final term called Glycemic Variability or GV. In measuring all these peaks and troughs related to food, we realise that a gentle pattern like a sine wave is much preferred to a jagged saw tooth pattern with huge swings.

There is now realisation that GV holds the key to all the dreaded complications we see in diabetics from the eye problems leading to blindness, to the deadened nerve endings that result in gangrene and amputations and to the kidney disease that ends in dialysis. We have also seen the hidden hand of GV in increased rates of heart attacks, strokes, hospitalisation and mortality. There is also suggestion that it may impact cognitive function, predict depression and accelerate formation of cancers.

Continuous glucose monitoring

With the advent of continuous glucose monitoring in the last few years, we have started looking at the GV with more granularity. Abbott is taking the continuous glucose monitoring system to the next level with its latest system recently announced in September, that will automatically deliver continuous real-time glucose readings to a user’s smartphone every minute. This is a major enhancement from its current system of measuring blood sugars every 15 minutes. Previously we could only measure a three-month average of blood sugars or ask the diabetic patient to prick himself seven times daily to give us an idea of how his blood sugars varied throughout the day.

So why is GV such a potent force? The jury is still out but there are some who think it mirrors the release of insulin and insulin triggers fat deposition in our bellies or what is called visceral fat. The visceral fat is different from fat on your thighs and buttocks. This visceral fat is like an “alien” organ. It releases all kinds of bad hormones and cytokines that increase the risk of heart attack, strokes and even cancer.

Can we then do something about the GV? The answer is obvious: if you know what kinds of meals spike your sugar or if you go hypoglycemic at night, you can change your diet and cut out foods that trigger the peaks and eat in a way to nullify the troughs. The way we respond to certain foods is quite individual and the GR may be different for different individuals and different foods; it is like you have your own individual pattern. Until you put on a glucose monitor, you cannot really tell.

The real benefit ultimately is to smoothen out your peaks and troughs with a combination of judicious and timed food intake, appropriate exercise and sound sleep, and the kilograms should come off as well as the centimetres off your waistline as you shed visceral fat. After all, all of us wish for a better quality of life and that quality reflects how we feel, move and look.

The Smart Watch: Telemetry For Humans?

GOOD nutrition, clean environments, accessibility to good healthcare and healthy lifestyles have increased human longevity. Nevertheless, the quest of increasing longevity is insatiable. As medical science pushes the boundaries of human lifespan, delving into the science of longevity can help us sieve through the reams of information and distil the essence of anti-ageing and cell preservation.

Cellular ageing

Cell ageing or cellular senescence is a physiological state with permanent cessation of the ability of the cell to replicate and accumulation of damaged DNA ( basic building blocks of genes), and this process is increased by ageing. This cellular senescence is marked by shortening of the protective terminal ends of the chromosomes which are called telomeres. Telomeres are like plastic caps at the ends of shoelaces, preventing them from being frayed and damaged. Shortening of the telomere is a sign of cellular senescence. In 1979, the first of the SIR (silent information regulator) proteins or sirtuins was reported. Over time more members of this protein group were found. In 1999, the publication of a study that reported that increased sirtuin activity could increase the lifespan of yeast cells by 70 per cent heralded a major breakthrough that accelerated the interest and research in sirtuins. Since then, there has been a growing body of evidence that the cell has a group of anti-ageing proteins, the sirtuins, that are essential for delaying cellular senescence and increasing the lifespan of organisms.

Anti-ageing proteins

Core to the science of anti-ageing is this group of proteins called sirtuins. In human cells, there are seven sirtuins (SIRT 1 to 7) with various roles within the cell. Three of these sirtuins (SIRT 3,4,5) control the generation of power for the needs of the cells and function in the mitochondria (power generator which produce the energy for the needs of the cell) with roles in cellular antioxidant balance and lipid metabolism. Another three sirtuins (SIRT 1, 6, 7) control the genetic framework in the cell and function in the cell nucleus (the central core of the genetic material in the cell) with roles in gene expression and DNA repair. There is one sirtuin (SIRT 2 mainly) which control the environmental processes within the cell and function in the cytoplasm (the liquid content within the cell). As an analogy, if the cell is a factory, the sirtuins are the executive management of the company directing and controlling all the aspects of the cell’s activities. They play important roles in maintaining the integrity of the cellular genetic structure, keeping the genetic material (chromatin) in a “wound up” protected state to reduce damage and in repairing damaged DNA.

Mechanisms of action

The main mechanisms of suppression of cellular senescence by sirtuin activity is via the actions of preventing telomere shortening or attrition, and promoting the repair of damaged DNA. Many proteins in the cells have a chemical tag called an acetyl group attached to it. One of the key ways in which sirtuins work is by the removal of the acetyl group from other molecules or proteins, thereby affecting the activity of the protein. This action has significant impact on the control centre of the cell, namely the activity of the genetic material or chromatin.

The basic building block of the genetic material, the DNA, is wrapped around groups of proteins called histones allowing the genetic material (chromatin) to be packed more compactly. When the histone protein has the acetyl group chemical tag , it causes the chromatin to be partially unwound and hence exposing the unwound DNA to be copied, thereby allowing the gene instruction to be passed to another cell or protein. As an analogy, it is as if a door to the office is opened and people are allowed to go into the office to copy instructions which are then passed to other offices. Once all the instructions are copied, the office door is closed. Hence, once the task is completed, the chromatin will not remain unwound as it will be more vulnerable to damage if it remains open.

Subsequently, the sirtuins can then remove the acetyl group from the histones which will then allow the chromatin to be closed by being “wound up” tightly, preventing DNA material from being copied and in effect silence the gene. Besides histones, sirtuins target other non-histone proteins such as proteins involved in copying genetic information and proteins that are involved in the repair of DNA. They are also known to regulate the production of the enzyme telomerase which is required for telomere elongation and maintenance of the integrity of the telomere. Most human cells have insufficient telomerase and hence there is progressive shortening of the telomere which is strongly indicative of progressive cellular ageing. Elongation of the chromosomal telomere is tantamount to reversing the biological clock.

Beneficial effects of sirtuin activity

Studies have shown that sirtuins have roles in the regulation of copying of gene information, modulation of energy production, prolongation of cell survival, reduction of DNA damage, reduction of cell damage and prolongation of longevity. Increased sirtuin activity in mammals has been associated with a delayed onset of age-related diseases and an increase in longevity. Sirtuins appear to be able to inhibit axonal (nerve fibre) degeneration, a process that often precedes the death of nerve cells as seen in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease.

It may also have protective effect on nerve cells, reducing processes that lead to the death o f nerve cells and the development of Alzheimer’s disease. Loss of sirtuin activity has been implicated in the development of cardiovascular and metabolic diseases including degeneration of arteries, acute damage to the heart muscle, thickening of the heart muscle, abnormal heart rhythms, high blood pressure, obesity, diabetes mellitus and abnormal lipid levels. While most of the studies have been done in animals, there is an increasing number of human studies.

There is presently an increasing body of evidence that shows increased sirtuin activity is indispensable for delaying cellular senescence and appears to protect the body against many age related diseases. In addition, studies support the role of sirtuins as anti-aging agents and potentially prolong longevity. Hence, lifestyle, dietary and pharmacological choices that increase sirtuin activity can potentially increase the anti-ageing effects and prolong longevity. These will be discussed in the next article where we will examine how we can make better decisions to increase our quality of life and lifespan.

Belly fat is the biggest enemy in fight against obesity

A combination of a healthy diet and exercise can get rid of the extra kilos and decrease the risk of developing diabetes

My patients have been complaining of weight loss or weight gain since the circuit breaker was initiated. Those who have lost weight were very concerned that they had an illness of sorts. Some of them had lost substantial weight – 5-8kg. We did the necessary and made sure there were no sinister causes. So, what had happened to my patients who lost substantial weight? Well, I figured out that they had change in lifestyle; there was a change in diet with eating and cooking more at home. Those who previously travelled extensively had stopped eating and drinking on planes, and had to give up entertaining or being entertained. All this resulted in a healthier diet; cooking at home involved healthier ingredients, produce and oils. The other big change is exercise.

With so much time on our hands and working from home, most of my patients ended up doing more exercise. Some started with walking, graduated to running and high intensity interval training. The gyms were closed and so quite a few ended up with cycling. There  was also a lot of online yoga, Pilates and aerobics being done. Underneath all these changes in lifestyle, there were also mental changes. There is loss with all that has happened – loss of liberty, loss of travel, loss of connection, loss of relationships, economic loss. And some of the losses would be only realised somewhere in the future. With such loss, a grief reaction was inevitable and there would be denial, anger, bargaining, sadness and finally acceptance. Some of my patients, without realising it, had slipped into depression or a milder form of it called dysthymia.

These were all characterised by weight loss, insomnia, loss of drive, loss of pleasure and libido with depressed mood. Some felt hopelessness with loss of focus and concentration as well. As we move into a lull phase of the pandemic in our nation, we still have to contend with the economic losses and unemployment ahead, with possibility of resurgence of the virus at any time. The prior losses, current bleakness and future potential losses have been instrumental in affecting our mental state. What about those who had gained weight? The majority had increased their intake for various reasons and had not matched it with exercise. One of the biggest drivers of ill health in today’s world is being overweight and obesity. We use body mass index (BMI) of 25 and above for overweight and 30 and above for obesity. For Asians, we actually found that we are worse off at those criteria and we use 23 and above for overweight and 27 and above for obesity.

Our local obesity rate is about 10 per cent of our population. Depot for fat cells The biggest enemy in our battle is the presence of visceral fat. Visceral fat is also known as “belly” fat and is different from fat on your thighs and buttocks. The visceral fat is actually deposited in the omentum – an apron that surrounds our intestines. The omentum is actually the transparent skin that gives the meat sausage its shape. It is also the biggest depot for fat cells. This fat is different because it generates cytokines; these are proteins that are generated by the immune system. You may have heard of the role of cytokines in desperately ill Covid-19 patients undergoing a “cytokine storm”. We know that these cytokines, including proteins named interleukins, tumour necrosis factor, adiponectin and leptin,  are powerful drivers of insulin resistance and inflammation and ultimately leading to an increased risk of diabetes, hypertension, heart disease, stroke and even cancer.

How does one know that he or she has visceral fat? A simple tape measure of the waist circumference around the navel and a measurement of 80cm and above for women or that of 90cm and above for men is indicative. So, how did we know all this? In 1986, there were more than 100,000 patients in Da Qing with prediabetes and they were subjected to diet, exercise and combination of both for six years. The outcome was that those who did nothing went on to develop diabetes, while those who went on a diet reduced their chance of diabetes by 31 per cent, those who exercised by 46 per cent and those who did both diet and exercise by 42 per cent. In the same year, a study of more than 40,000 nurses over the next eight years by Harvard showed that women with obesity, a high waist-to-hip ratio and a waist circumference of 92cm and above were more 11 times more likely to develop diabetes.

So, what do we have to do about visceral fat? We have to make sure our sugar levels do not spike as our insulin levels will also mirror such a spike to get rid of the sugar. The insulin works like a key and opens all the cell doors in your body so that the sugar load in your blood will move into cells to burn for energy. Avoid a sugar spike The main driver of visceral fat formation is actually the high insulin level. So in this case a sky high level of insulin is the “bad boy”. Hence, we have to eat carbohydrates that don’t give us a sugar spike.  These include healthier options such as cooked oatmeal as opposed to instant oatmeal, glass noodles, Japanese noodles like soba and udon and Italian pastas. The ones to avoid are white rice, white bread, potato and yellow noodles. Fruits are also high in sugar and these include pineapple, mango, melons, banana, grapes, lychee and longans. The idea then is to eat carbohydrates that turn slowly to sugar.

These are called Low Glycemic Index (GI) foods. Hence, the quality of the carbohydrates and the amount of the carbohydrates also matters. When you factor both quality and quantity of the carbohydrates you get something called Glycemic Load (GL). When you attach a glucose monitor onto your arm that measure your blood sugar levels every 15 minutes for a period of two weeks, we get nice graphs of your sugar peaks and troughs. When you annotate these beautiful graphs with the foods you eat, you get something called a Glycemic Response (GR). We have analysed patients with such graphs using machine learning tools software and found some interesting findings. We found that sometimes what you think is healthy may not be so. I used to eat oatmeal with blueberries every morning and thought that was extremely healthy. It turned out that it spiked my blood sugar sky high.

I have a patient whose sugar spiked through the roof every time he ate any kind of bread including wholemeal. The message is clear, each individual’s GR is different; pretty much like a thumbprint. You may have to attach a glucose monitor to find out. The final analysis is that we think that there are certain foods that you are eating and these are likely to be your favourite, and hence frequently consumed, foods that are really affecting your GR and making you pile on visceral fat. You can boil all this down to an adage: there are foods you want to eat, there are foods you should eat, but ultimately you have to figure out which foods you can eat.

Getting a flu shot is a good idea right now

The year-end and the yuletide season will be soon upon us. Ordinarily we would be gearing to go travelling and some of us would be headed to cold temperatures in the northern part of the globe. However, this has been anything but an ordinary year. We have been beset by a once-in-a-centenary event of a pandemic. As we speak, the pandemic has claimed its one millionth victim and shows no signs of abating. We are all resigned to tracking with bated breath the progress of the 11 Covid-19 vaccines in Phase 3 human trials as there seems to be no other way to stop the onslaught of the coronavirus. Yet we should not be so helpless; we can still do our part by getting our influenza (flu) vaccines. The influenza vaccine is important at this juncture in our fight against the pandemic.

We should first understand that influenza attacks vulnerable groups especially in winter. We do not have a winter season but up to recently we have had a mobile population that travelled extensively for leisure and business; and we used to have 20 million visitors annually. Despite being at the Equator and having tropical climate, we are also an air-conditioned nation. All these factors can make us more susceptible to influenza and its spread. The more vulnerable among us include young children, those who are pregnant and seniors, especially those with chronic diseases and ailments.

Risk to vulnerable groups
Influenza vaccines are recommended for these groups and in the midst of the pandemic, it is imperative that we get them vaccinated to avoid the difficulty of telling apart the Covid-19 infection from the common cold or influenza when patients present with respiratory illnesses. We can also prevent hospitalisation or events related to flu that may increase the risk of the vulnerable groups to Covid-19. We are often asked which flu vaccine we need to take. There are two flu vaccines in a calendar year. The Northern Hemisphere vaccine is available around this time of the year while the Southern Hemisphere vaccine is available in March. The names of Northern and Southern refer to the winter seasons that are critical to patients who contract influenza. The winter season tends to exacerbate the influenza and lead to complications and ultimately the demise of the vulnerable patients. As a result we tend to vaccinate prior to the arrival of winter.

We also need to understand the logistics of producing a flu vaccine. The initial research is to figure out what flu strains will be active in the winter ahead. This involves some degree of “crystal balling” to identify the strains the vaccine should be effective against. Sometimes the prediction is correct and sometimes it is not. It takes, on an average, five months for the pharmaceutical firms to produce, ship and have a vaccine made available. We will usually offer the vaccine that is currently available. Sometimes because the pharmaceutical firms have to make an educated guess as to which flu strains will be causing problems in the winter ahead, we have a situation where if one takes the prevailing vaccine, there is still a chance that we have to take the next vaccine that comes out six months later. So you may hear of people taking two flu vaccines within six months of each other. Fortunately we have guidance on this from our Ministry of Health.

While we are in the midst of a pandemic, we should look back at history. We had the infamous Spanish flu pandemic in 1918 that spawned the H1N1 virus that came from birds. There were smaller pandemics in 1957 (H2N2), 1968 (H3N2) and the recent H1N1 in 2009. I was fascinated by the stories of scientists who discovered the genome of the Spanish flu by exhuming the bodies of Inuit natives who died in 1918. The lung tissue of these bodies was well preserved by the permafrost in Alaska. The scientists managed to extract the RNA of the virus from the preserved lung tissue, decipher it and reconstruct the actual virus at the CDC Laboratories in Atlanta, Georgia. As for the 1957 flu pandemic, my Italian patient in his 70s recall contracting the flu in 1957 as a young boy and told me that he was so ill that he was in bed for three weeks.

Global fight
We are always faced with mutating flu strains and the latest is a swine flu strain in China. This strain is H1N1 and has been spreading since 2016 in the Chinese pig herd. They have found that about 10 per cent of swine workers have been exposed to the virus. So far there has been no human-to-human spread but the local and global authorities are watching this virus like a hawk. This siege is the reality in our global and united fight against viral threats. One of the key battles is the speed of a vaccine against a novel virus. The vaccines take a long time to be produced and in the H1N1 pandemic in 2009, it took 26 weeks for a vaccine to be produced and shipped. We can technically reduce this lead time to 12 weeks but that will need a lot of resources and international cooperation.

A universal flu vaccine is still light years away. The comparison is the ongoing vaccine race for the Covid-19 vaccine. We had the published genome of the Covid-19 virus on the weekend of Jan 11/12 this year. As of today we have 11 vaccines in Phase 3 trials and five approved for limited use. These five include four Chinese vaccines and one Russian vaccine. In the midst of this pandemic while we wait for the Covid-19 vaccine, we must act and mobilise the population to get vaccinated against influenza. The latest flu vaccine is now here and I myself have taken it. While the use of face masks has reduced the incidence of influenza, it is still a good idea to approach your family doctor for a flu shot for all the reasons I have outlined above.

One reason is that it can help in differentiating the Covid-19 infection from the common cold or influenza when patients show symptoms of respiratory illnesses.

Living through a once-in-a-lifetime event

It has been 14 weeks or so since the first case of Covid-19 virus landed on our shores. A lot has happened since, with a wave of returning citizens bringing home the virus from epicentres in the United Kingdom, Europe and the United States. These 579 imported cases unfortunately spawned community spread and the outbreak in our migrant worker dormitories.

The community spread led to unlinked cases that started from nine daily to as high as 31 daily before we had to impose “circuit breaker” measures. With the initial and further stricter measures, we have now brought the unlinked cases down to an average of 11 daily in the last week.

To date, Singapore has reported 21,707 Covid-19 cases in total, with more than 19,000 of those being migrant workers in the big dormitories and smaller factory converted dormitories. There are 200,000 workers in the big dormitories that can house up to 20,000 workers each, and 100,000 workers in the smaller factory dormitories that house as few as 20 workers.

The dormitory outbreak has challenged our nation in many ways. The logistics challenges are huge; agencies have had to deploy medical posts in the 43 big dormitories, impose restrictions on movements within these dormitories, swab huge numbers of sick migrant workers, move and house them in communal facilities to monitor them through their illness, and as they are recovering, move them to recovery facilities. The numbers in communal facilities total 10,000, a tally that is steadily rising and could soon double.

The agencies involved in such herculean efforts comprise both private organisations and public agencies. This private-public cooperation is heartwarming to see, as Singapore Inc mobilises under threat from this invisible enemy.  There has been criticism of the living conditions of the dormitories but I cannot think of any other nation that has mobilised in such a manner to look after their migrant-worker population.

The other challenge is the healthcare system and the effort to protect it from being overwhelmed. All the herculean effort on the dormitory scene is really to flatten the curve of the epidemic to prevent a massive surge of cases that may overwhelm the ICUs, high dependency units and oxygen points.

Though we have reduced the number of unlinked cases in the community, we are concerned that an outbreak in nursing homes will mimic that in the dormitories. The migrant workers are young and fit due to the nature of their job. The data shows that of those who are 30 years old and below, less than one per cent will need oxygen of any sort.

Hence the huge numbers of migrant workers who have caught the virus have not translated into huge demand on our ICU beds. But a sizeable outbreak in nursing homes will be of a different nature. On the testing front, the number of swabs has increased from 3,000 daily to 8,000 daily currently, and the number of swabs will be further increased five-fold. This is a huge ramp-up, with laboratory workers working non-stop at breakneck speed since January, and the shortage of reagents and disposables as there are limited suppliers globally.

The swab processing is a laborious process; it involves extracting and amplifying minute amounts of viral RNA and takes six to eight hours to execute. The antibody test that can be rapidly deployed and which is as simple as a pregnancy kit has been disappointing. The antibody test detects the viral antibody effectively only after 11 to 14 days of symptoms.

Good ICU care

On the ICU beds front, we have the capacity to double or triple the number needed. Our ICU care is good and we have a low mortality rate so far, although the 20 patients that have perished is one too many. Hence for a drug treatment to be effective, the drug has to perform much better than our ICU care or stop patients from entering ICU. There is a lot of hype around remdesivir.

Trials failed to show that it reduced mortality, but it did reduce the recovery period from 15 to 11 days. To find a drug off the shelf and then to repurpose it for a novel virus is a difficult ask. It is likely that we need to develop a new drug from scratch. As for the vaccine, there are three phases: the first involves 10 to 30 patients and you are looking for immune response and safety; the second phase is with larger numbers of 100 to 300 patients and you are still looking for safety and immune response. The third phase is real-world deployment with placebo-controlled randomised trials.

Realistically, this will take 12 to 18 months, and anything can go wrong during the three phases; then it is back to the drawing board. The race is on between the US and China for a vaccine, making this a geo-political race for prestige and prowess. This pandemic is a combination of health, economic and psychological crises all rolled into one. I would leave the economic aftermath to the economists and have a word about the psychological state of our globe. I like what author and public speaker David Kessler has said about this crisis – that it is a grief reaction.

Mr Kessler and his late collaborator Kubler Ross gave us the definitive stages of grief reaction.

The grief we feel is that of loss of normalcy, fear of economic loss and loss of connection to our social circles. The nature of the fear we feel is somewhat in the future; we dread the fear in anticipation. It is sort of like when a loved one is diagnosed with cancer – we dread the future of the disease and what it brings for us.

The stages of grief starts with denial, where we are sure the virus will never reach our shores and will go away. The next phase of anger results in us blaming that person for coming too close to us, or blaming another nation for the pandemic.  Bargaining makes us think if we take pills or supplements, it will not infect us. Sadness permeates us as we wonder when it will all end. The penultimate stage is acceptance where we decide we have to take control of the situation; we have to execute a series of actions of washing our hands, masking universally and working from home.

When we have a plan and execute it, we regain control and fulfil acceptance. There is an ultimate phase of grief reaction and that is to find meaning. We have encountered a once-in-a-lifetime event that has disrupted our lives, halted the economy dead in its tracks and left us hiding in our homes in a curfew-like situation. The virus has infected millions globally, killing a quarter of a million, decimated mighty economies and left the world in fear, grief and resignation.

Positive aspects

Yet there are silver linings. The skies are blue, the local PSI has halved, the dust on surfaces has reduced and wildlife and migratory birds have re-emerged. Our family life has become central, there is daily bonding over family meals, young children are amazed that parents are home daily, and exercising with children is a norm. Working from home has made workplace hierarchies less relevant, savings have accrued from reduction in transportation, meals and clothing; staff may actually need less renumeration with reduced costs, office space may shrink as most work can be done from home with today’s technology enablers. The need for helpers and the disincentive of the helper’s levy should be revisited.

That work is also a social need is important; offices may well become meeting places rather than workplaces. With the gradual reopening of the economy and the new normality we have to accept that there will be pain and loss of jobs, assets and destruction of value. This is a time to rally the nation round to face the hardships and the uncertainties the future holds. We have to form alliances, and we have to seek other nations to rebuild our economies together. Our leadership has to pull this off and navigate us through these uncharted waters.

The old adage is true – in the midst of crisis, there is opportunity to re-examine, realign and re-energise our values, our priorities and our prowess.

The race is on to seize the day.

Understanding the ‘cytokine storm’ that is Covid-19

I was on vacation in Japan around Christmas when I first heard the news on CNN, of a strange virus that was causing pneumonia in a cluster of patients in  Wuhan. On reading the report on my smartphone, I felt a shiver down my spine. This was because the description of the illness resembled the “cytokine storm” of the Sars virus. The shiver down my spine was prescient; as of current writing we are in Dorscon Orange with 86 patients diagnosed, 5 in intensive care and 47 patients discharged and well.

In China, despite the heroic and unprecedented actions of locking down an entire province, the epidemic rages on. The silver lining is that the heroic actions by the Chinese have bought us some time for our local actions to take effect. So what is this “cytokine storm” that you keep hearing about? In essence when a virus attacks a host, it is like an invasion. The virus lands on a beachhead – in humans it is usually in the throat – and starts multiplying in large numbers.

When there is a high viral concentration or viral load, the virus enters the blood stream or moves through lymphatic system or via secretions, and can spread to other organs. In the case of Covid-19, it spreads deeper into the lungs where it targets a receptor called the Angiotensin Converting Enzyme receptor. Why do some patients have a mild disease while others are warded in intensive care? This is because when there is a huge viral load, the body responds massively. In healthcare workers, our immune systems are constantly challenged as we meet lots of patients daily and are exposed to the viruses or bacteria that they carry.

Our immune system is primed to deliver an overwhelming response especially in the face of a huge viral load. It is precisely this overwhelming response that may make us very ill and be warded into intensive care. So, you may not realise that our healthcare workers are under a great deal of stress during this period as our risk is way higher than the average patient.

As for the public, what should they be aware of so that they can help themselves? We know the virus is spread via droplets. This means that when someone coughs, the droplets fly through the air for about 10 feet (three metres) and settle on surfaces. The mucus in the droplet protects the virus whilst the droplet is on a surface. The mucus usually dries up in 30 to 60 minutes and the virus dies. However, when an unsuspecting person touches the surface with his hands and  then proceeds to touch his eyes, face or hair, the virus can then be transmitted. The entry to a host is usually via mucus membranes; these line the inside of our mouth, nose and eyes. As for the hair, the droplet can cling onto hair and be protected by headgear. Hence, I tell my patients that hand hygiene is of the utmost importance and they must always wash their hands before they touch their eyes, face or flick their hair.

Do we really need to use hand sanitisers for hand hygiene? The reality is that soap and water will do. We also know that the coronavirus is quickly inactivated by plain tap water. However, we must get rid of the mucus envelope that protects the virus. Hence the soap is useful and for surfaces we need to ensure that the droplets with attendant load of mucus is cleaned off. We then come to masks. The current advice is that masks are useful for preventing those who are sick from infecting those who are well. The surgical mask is enough to stop droplet transmission.

There is no need to wear the N95 mask. In fact, when you wear the N95 mask for a period of time, you will get fatigue from breathing against resistance. Therefore, we do not encourage patients with chronic heart or lung diseases to wear N95 masks routinely. For healthcare workers who wear N95 masks for a long duration, we do feel the effects of that added work of breathing at the end of the day. For those who are well, should they wear masks? The perspective is that we have 30,000 to 35,000 patients daily in Singapore with upper respiratory infections of all sorts. Maybe a couple of hundred will be pneumonia cases and Covid-19 infections will probably number less than two handfuls. The idea is to avoid crowds as we cannot contact trace a crowd of people. However, I tell my patients that life must go on and if you are meeting your family members, friends and colleagues for a meal, contact tracing is simple as you know everyone.

As for fear of the virus, this is the stuff that epidemics are made of. The difference between Sars, H1N1 and the current situation is that the feed from social media is massive. We are constantly inundated by chats, videos and articles coming through our smartphones. The fear captures and amplifies the individual’s mind and soon he or she starts to think or say things in an illogical manner. This is so obvious when you are reading the feed from chatgroups.

When we are angered by a close shave, such as when an office colleague is ordered to be quarantined, we tend to think the worst of our colleagues. When we are fatigued and tired at the end of the day from our workload and our worries about the virus, and we read of the demise of the eye surgeon in Wuhan and his pregnant wife, you think of the safety of your family and are worried sick. When we receive news or read something that reflects our emotional state, our brain tends to amplify or exaggerate the pervasiveness, degree and severity of that situation.

It is important that we trust the experts, or make sure that our news comes from reliable sources and sieve out misinformation and fake news. Please do not believe claims that the virus is airborne, conspiracy theories on the origin of the virus, need for the whole population to wear masks or false claims about the competence of health authorities and governments. In Singapore, our leadership has the institutional memory of the Sars epidemic and the dress rehearsal of the H1N1 pandemic. We also have the logistics, preparation and the physical capability in terms of isolation rooms and intensive care. Most importantly, the leadership has the political will to take tough action when necessary and the people will listen, respond and act responsibly when we need to. As we speak, the Public Health Preparedness Clinics are being activated. Do spare a thought for our healthcare workers as they strive and struggle in the days ahead, often with their own burdens, fears and tensions pushed aside for the heroic task at hand.

Feasting or fasting in the festive season?

THE Christmas festivities are barely over and Chinese New Year is already rolling round. We have just recovered from the wine and dine of the Yuletide season and are trying to shed the extra kilogrammes. The gym instructors will tell you that there is a surge in the beginning of the year in gym attendance as people grapple with added body weight and the weight of their New Year resolutions! There has been a lot of interest in intermittent fasting and low carbohydrate diets. Intermittent fasting is practised in various ways. One is to fast on alternate days or to fast two to three days in a week, while an alternative way is to reduce the number of hours in a day for eating.

Hence you have regimens such as 5:2, where you fast for two days in a week, or fasting for 14 hours daily for five days in a week and gradually increasing it over months to 16 to 18 hours daily. The whole idea about intermittent fasting is to switch the body to use ketones as a fuel as opposed to glucose. The brain needs to use glucose to power itself and in fasting states, it uses ketones. The ketones comes from fat breakdown.

Caveman situation

The idea of intermittent fasting is to recreate the caveman situation where they did not cultivate crops and had to survive from hunt to hunt. The fasting state induces ketone production or ketosis and it takes only eight to 10 hours of fasting before ketones start to rise in the bloodstream. The rise is marked when the fasting period hits 24 hours. The ketones are not just a fuel; they are also powerful triggers of certain pathways that the body needs to overcome the challenge of fasting. These pathways allow the cells to mount antioxidant response, repair damaged DNA, increase number of mitochondria that are the powerhouses of the cell, remove damage structures inside the cell and reduce inflammation.

In short, the body conserves by shutting down growth and reproduction, enhancing response to stress, favouring repair mechanisms and ensuring cell survival. When the fast is broken and the patient starts to eat, the glucose levels rise, the ketones fall, the body starts to increase protein production resulting in growth and repair. Hence the intermittent fasting regimen together with exercise results in long-term adaptations that are useful. Is intermittent fasting the panacea to our growing obesity rates globally? There is a lot of research ongoing in different areas such as intermittent fasting in cancer, degenerating illnesses of the brain, asthma, autoimmune disease, diabetes, obesity and cardiac diseases.

A lot of data is in animal studies and we are still missing long-term, megasized trials. Other issues include gorging during the feeding states as you still have to restrict your calories when you break the fast; there is also irritability, hunger and “brain fog” when your brain starts using ketones as a fuel. Thankfully, these side effects resolve within a month of starting your regimen. The other popular strategy is the use of low carbohydrate diets. A healthy diet comprises of 45 to 65 per cent of carbohydrates. A moderate carbohydrate diet comprises 26 to 44 per cent, a “low” carbohydrate diet is 10 to 25 per cent and a “very low”  carbohydrate diet is 10 per cent or less. The remaining is either protein or fat. The diets that trigger ketosis are usually low or very low in carbohydrate and high in fat. High protein intake in a low carbohydrate diet can negate ketosis.

Does a low carbohydrate diet work? The data shows that such diets do work, and they can result in increased metabolism. We are not sure how this is achieved but it could be due to changes in stress and thyroid hormones. There is also remarkable initial weight loss due to loss of body water as ketones are diuretic in nature. The loss of water is also due to lower insulin levels and the depletion of the glycogen stores in your liver. The weight loss in the short term is much better than your normal low fat diet. In the longer term, that is, six months or more, the gains between low carbohydrate and low fat diet evens out. It is also very  difficult to sustain a very low carbohydrate diet. The other thing to note is that your muscle mass may also deteriorate with low carbohydrate diets and so it is important to make sure you eat enough protein and not just fat.

I am often asked if cholesterols will be affected by a low carbohydrate diet. The response of cholesterols levels may be quite varied. If the patients eats a lot of saturated fat, the LDL or bad cholesterol will rise. Hence we usually tell patients on such diets to monitor their cholesterol profiles. The triglycerides are heavily influenced by glucose and hence such diets do lower triglycerides. In diabetic patients, the triglycerides and blood glucose levels are reduced by such diets.

Not all diets are equal

Among the low carbohydrate diets, not all are equal. For example, they found the diets that were more Mediterranean and Paleolithic in nature were useful in diabetics. Those with higher protein and lower fat were also useful. Is there a down side to such low carbohydrate diets? Well, they found that it was not helpful in blood pressure patients, it may produce changes in the gut bacteria and it is not helpful with inflammation. We believe that the arteries are inflamed, therefore triggering blockages. Is there increase in longevity if we partake in such diets? The data shows that if we substitute the carbohydrates that we forego in such diets with animal fat or protein, longevity is reduced.

However, if we use plant-based fat or protein, longevity is enhanced. In the final analysis, we have found that patients do lose weight with low carbohydrate diets and intermittent fasting. We have to be aware that such diets are not fads or trick diets. One can lose weight by cutting off a leg; “trick diets” try to get you to reduce your calorie intake by making you consume too much of one item, be it pineapples or apples or whatever. Ultimately, as we leave one festive season and move into the next, be mindful of what you eat, try to eat in moderation, control your portion sizes, maintain your exercise and enjoy the goodwill and fellowship of kin, friends and colleagues.

Dr Chong Yeh Woei
Senior Physician (Internal Medicine)
MBBS (S’pore), MRCP (UK) Internal Medicine


Ready to run on the big day?

Some vital dos and don’ts that will ensure you have a memorable marathon experience

Singapore marathon fever is upon us once again. And it is going be a momentous event for a lot of us. You probably have been training for this for the last few months with building up your weekly mileage, enduring weekly long runs, doing speed work with interval training and, last but not the least, letting your body rest and recover. By this time, you would have scaled back on your training in preparation for the big day. So how tough is it to run a 26-mile race? The first person to run the marathon, a Greek soldier called Pheidippides, collapsed and died. Currently, the best marathoners in the world are invariably the Kenyans; they run the race in a little over two hours. The main fuel to support a marathon comes from glycogen. The main storage of glycogen is in the liver and the muscles which provides enough fuel for about two hours. Hence, if you take more than two hours to run the race, you have to top up your fuel supply, usually by eating.

Fuel for a run commonly comes in the form of bananas, chocolate or energy gels. The energy gels contain carbohydrates in form of maltodextrins and glucose with potassium and sodium. Maltodextrins are long chains of glucose molecules. They are pre-digested simple carbohydrates and resemble the food that has been digested by the stomach. Hence the absorption is rapid in the intestine. These maltodextrins also serve the purpose of being isotonic with little water needed. The thing to remember is that you got to accustom yourself to drinking isotonic fluids while taking these gels on the run prior to the big race. It is recommended for an average runner to take a gel patch every 30-45 minutes in a marathon. The other important thing to consider is your hydration status. You should hydrate yourself adequately during the last week prior to race day. You should, by now, be able to gauge how much fluid you would need during the training runs in the same humidity and temperature. Hence, on race day you would know how to drink appropriately. One should not depend purely on the sensation of thirst before drinking.

Often, when you feel thirsty, the body is already dehydrated. Thirst is regulated by a centre in the brain stem which senses the concentration of the circulating blood. When the blood concentration rises, the brain stem sends a signal to the body giving you a sensation of thirst. This signal is often ignored during a run when there is too much excitement and euphoria. There is also a risk when one drinks too much. This is commonly seen in the slower runners who would be drinking more at water stations and yet sweating less. That can lead to a situation called hyponatremia, where the sodium level in the blood drops due to dilution from over-drinking. This can cause altered mental state and confusion. This brings us to the matter of a runner who collapses during the run; it could be from hyponatremia, heat disorder, low blood sugar or from a heart condition. In our hot and humid climate our major concern is heat disorder.

The temperature in the body rises from dehydration, excessive heat production due to running and the lack of heat dissipation from our warm and humid weather. Heat disorder is quite insidious and must be recognised by the paramedical and medical personnel deployed during the race. The immediate treatment is to get the collapsed heatstroke runner into a body cooling unit before evacuating him to hospital. Wearing the right shoes is important too, and for most of us, cushioning shoes are critical to buffer the constant pounding on the road. Some of us are flat-footed and need motion and stability control shoes. Some runners buy special socks; wearing light mesh clothing is useful in our climate, as well as applying Vaseline to chafing parts of our bodies. Chafing is caused by constant rubbing of the moving body parts against the running gear which causes the bruising of the skin. The common sites are the nipples, the groin and the armpits. The conditioning of the mental state is as important as the physical preparation.

The feeling of not being able to complete the race comes soon after the euphoria during the start of the race has evaporated. This is compounded by the heat, loss of stamina to complete the 26 miles, and low body fuel. Some runners listen to music to distract themselves, carry on a conversation, or merely admire the environment and the cheering crowd. Positive thinking helps tremendously to minimise the awkward feeling of not being able to complete the race. When you have completed the race, head for the medical post if you are feeling unwell. Otherwise, keep moving as there can be risk of fainting due to venous pooling when the overworked muscles suddenly become inactive. Do make sure you drink water and isotonic drinks. When you have reached home, continue to drink water and isotonic drinks and listen to your thirst. Do eat protein-laden and carbohydrate-rich food. You should continue to move around and do get rest, naps and a good sleep to let the muscles and the heart to recover quickly.

Getting yourself a sports massage may also help and do not race competitively for a fortnight or more. If you have injuries, remember to ice, rest, compress and elevate the affected limb. You can take some an anti-inflammatory medication and, if in doubt, go see your family doctor for evaluation. Finally, do go out there today and enjoy your run that you have been training for quite a while. You don’t always have to finish it if you can’t and you don’t have to run it all the way.

Just listen to your body and you will have a great, once-in-a-lifetime experience.

Dr Chong Yeh Woei
Senior Consultant Physician (Internal Medicine)
MBBS (Singapore), MRCP (UK) (Internal Medicine)


What you should know about the various types of vaccines

Travellers especially should take precautions and depending on their destinations, go for the relevant vaccinations

I am often asked about vaccines by my patients; most of the queries pertain to travel, dengue, pneumonia and shingles.

It is interesting to note that most of our childhood vaccines are not compulsory under our laws in Singapore. I had always assumed that vaccines like BCG, polio, hepatitis B, pertussis (whooping cough) are mandatory but only diphtheria and measles are compulsory by law. I believe most parents in Singapore are very compliant with the National Childhood Immunisation Schedule.

In fact, childhood vaccinations have a long history in Singapore. Most people don’t realise that Singapore was one of the first nations in the world to start mass polio vaccination in 1958. We were also one of the first nations to start a mass hepatitis B vaccination programme for all newborns in 1987. As a result, we have managed to cut transmission of Hepatitis B from mother to child by 80 per cent or more. Some of the vaccines are not in the National Immunisation schedule and I am often asked about them. The rotavirus vaccine is for diarrhoea in infants and it is an oral vaccine so there is ease of administering the vaccine. The cost maybe a little daunting though.

The chickenpox vaccine is also useful as chickenpox scars can be quite traumatic for teenagers and everyone does not realise that as an adult, getting shingles is no laughing matter. I am often also asked about the vaccine for cancer of the cervix for young girls. This vaccine is now recommended in the National Schedule. I encourage my patients to send their young daughters for the vaccine as that would prevent cancer of the cervix. The best age would be before they become sexually active; the recommended age would be from 9 years of age onwards. Another vaccine that is quite unusual in the local context – except for people going for the Haj – is the meningitis vaccine. Most of the time, I am asked about this by parents when their child is going to university abroad especially in Europe, USA or Australia/New Zealand. The usual vaccine is called MenAWCY that protects against four strains or serogroups of bacteria identified by the letters.

Increasingly I am also asked by concerned parents about the meningitis B vaccine. At the moment on the CDC Atlanta website, there are three universities in the US that have outbreaks of meningitis B. Apparently there are quite sizeable populations in Western countries carrying the meningitis B strain especially in the varsity age groups. Approximately half of the meningitis cases in the Western world are now caused by this strain.

Another big group of patients are business travellers. A well-paying job in Singapore these days involves a lot of travelling in the region as companies expand overseas. I encourage business travellers to get the influenza vaccine annually. Sometimes the whole family shows up for vaccination prior to a holiday at year end to a winter destination.

This is sadly because they previously had a whole vacation ruined because they caught the flu bug.

Yet other travellers are encouraged to update their Hepatitis A and typhoid vaccines. They are both oralfecal in transmission. Hepatitis A can be quite debilitating, and the natural course may run for up to eight weeks.

Some patients may feel very fatigued for up to six months thereafter. Typhoid fever can be persistent and sometimes diagnosis is delayed; ultimately typhoid can be life threatening. The vaccines are tolerable and there is an oral and injectable typhoid vaccine.

Some of my patients get a fever with the typhoid injectable vaccine but it is usually resolved quickly with paracetamol. As for Hepatitis A, we can also test if the patient is protected against the virus with a simple blood test. About half of those aged 50 and above have natural immunity.

Some of my travellers ask me about tetanus. Most of us have been vaccinated against tetanus in childhood, hence the protection is good enough for a decade till the age of 21 years old. We are actually not worried about stepping on a rusty nail, but whether a wound is dirty. Animal bites are probably the worst and if one fell into a filthy drain, one should get a booster too. A good alternative to the tetanus vaccine is the combined tetanus, diphtheria and pertussis (whooping cough) Tdap vaccine. There is a resurgence of pertussis which is responsible for 10 per cent of emergency room patients presenting with cough.

As for animal bites, I caution travellers not to play with cats, dogs or monkeys when abroad. Singapore is rabies free but the surrounding countries are still endemic for rabies. When bitten abroad, the rabies vaccines and antibody shots should be administered immediately and are both costly and involve multiple injections.

Sometimes, patients ask me about Japanese B encephalitis. This is a disease with high fatality, but you need a mosquito to bite an infected pig and then transmit it to man. Since we have phased out pig farms in Singapore, it is very rare. We would recommend vaccination if one is travelling to certain endemic countries and staying for more than a month in a rural setting. In our local context, there is always the threat of dengue despite our world class mosquito control programme. In dengue infections, we are very concerned if there is a huge viral load coupled with an overwhelming response from the immune system of the patient. This often leads to severe dengue or dengue shock.

The current thinking is that we should vaccinate patients who had dengue previously. The data shows that if we vaccinate dengue-naïve patients; the body becomes primed for severe dengue illness when the infection does occur. In my older patients, I am often asked about pneumonia vaccines and shingles vaccine. The pneumonia vaccines are very useful. There are two available: one covers 13 strains (conjugate PCV13) and the other covers 23 strains (polysaccharide PPV23) of the bacteria that causes pneumonia. We recommend that all above the age of 65 years be vaccinated with both vaccines.

We usually advise that the patient be vaccinated with the conjugate vaccine first followed by the other vaccine a year later. This is to avoid the two vaccines affecting each other’s efficacy. Incidentally the conjugate vaccine is given to children under our national immunisation schedule.

Finally, we have shingles, which is a painful ordeal for patients. Some patients have it on their face and suffer a great deal. There is always the risk of post-shingles pain (post-herpetic neuralgia) that can go on for years. The pain has been known to drive patients to suicide.  The current single dose vaccine is available to those 50 years and older. A newer two-dose shingles vaccine offers very high efficacy, but it is not available yet.

A final word about the naysayers of vaccines; this is also known as vaccine hesitancy. There are many complex reasons for vaccine hesitancy; and social media and Dr Google have not been helpful. There are also the controversies such as Hepatitis B vaccine and multiple sclerosis in France in the 90s and the association of the MMR (measles, mumps and rubella) vaccine and autism. These have been found to be false but the damage has been done. There has been a drop in the coverage of the MMR vaccine in the US and UK with a rise in measles cases worldwide. There is an ongoing measles outbreak in the US originating in the orthodox Jewish communities in New York since October last year. The city has passed a law that prohibits exemptions from vaccines on non-medical grounds. This law will affect 26,000 school-going children in New York. Thankfully in Singapore, vaccine hesitancy has not been a big issue as our population believes that vaccines are safe, effective and necessary.

Dr Chong Yeh Woei
Senior Physician (Internal Medicine)
Singapore Medical Specialists Centre
MBBS (S’pore), MRCP (UK) (Internal Medicine)

The Business Times Weekend, 21 September 2019