COVID-19 and cardiovascular disease

COVID-19 and cardiovascular disease

OVERVIEW

  • People with cardiovascular disease are more likely to develop the more severe forms of COVID-19, which significantly increases the mortality rate of this disease.
  • In addition to being an important risk factor for COVID-19, cardiovascular disease can also be a consequence of SARS-CoV-2 coronavirus infection.
  • Patients with severe COVID-19 frequently have heart damage, which increases the severity of the infection and is life threatening.

COVID-19 is a respiratory disease caused by a new virus, the SARS-CoV-2 coronavirus. The COVID-19 epidemic began in December 2019 in Wuhan, Hubei Province, China, and has spread rapidly worldwide with more than 1,360,000 people affected and 75,973 deaths as of April 7, 2020. Although most patients infected with the virus do not have major symptoms, about 15% of them develop a much more severe form of the disease, including severe acute respiratory syndrome that requires mechanical ventilation. This severe form of COVID-19 is particularly dangerous for the elderly: while the mortality rate is around 1% among those aged 50 and under, it rises to 3.6% in those aged 60, to 8% for those aged 70 and up, and to 14.8% for those 80 years and older.

An aggravating factor: Chronic diseases
Data from previous outbreaks caused by coronaviruses similar to SARS-CoV-2 have shown that a large proportion of infected patients are affected by underlying chronic conditions. For example, during the 2002 severe acute respiratory syndrome (SARS) epidemic, the prevalence of type 2 diabetes and preexisting cardiovascular disease was 11 and 8%, respectively, and the presence of either of these chronic conditions was associated with a very large increase (almost 10 times) in the mortality rate. Similarly, in patients infected with Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 and presenting with severe symptoms, 50% suffered from hypertension and diabetes and up to 30% from heart disease.

The presence of these comorbidities (coexistence in the same patient of two or more diseases) is also observed during the current COVID-19 epidemic. In all the studies carried out to date, a significant proportion of patients were affected by a preexisting chronic condition, the most common being hypertension, type 2 diabetes and cardiovascular disease (Table 1).

PopulationComorbiditiesSource
99 infected patients
(Wuhan, China)
Cardiovascular disease (40 %)
Diabetes (12 %)
Chen et al. (2020)
191 infected patients
(Wuhan, China)
Hypertension (30 %)
Diabetes (19 %)
Cardiovascular disease (8 %)
Zhou et al. (2020)
138 infected patients
(Wuhan, China)
Hypertension (31 %)
Diabetes (10 %)
Cardiovascular disease (15 %)
Wang et al. (2020)
1099 infected patients
(China)
Hypertension (15 %)
Diabetes (7.4 %)
Cardiovascular disease (2.5 %)
Guan et al. (2020)
46,248 infected patients
(China, meta-analysis)
Hypertension (17 %)
Diabetes (8 %)
Cardiovascular disease (5 %)
Yang et al. (2020)
355 deceased patients
(Italy)
Hypertension (76 %)
Diabetes (36%)
Cardiovascular disease (33 %)
Atrial fibrillation (25 %)
Cancer (20 %)
Instituto Superiore di Sanita (2020)

In all cases, these chronic conditions are more frequently observed in patients with the more severe forms of COVID-19. For example, a study carried out in Wuhan showed that the proportion of patients with hypertension, type diabetes 2 and cardiovascular disease is almost twice as high in those who have developed a severe form of COVID-19. This contribution of chronic diseases to the burden imposed by COVID-19 seems particularly important in Italy, one of the countries hardest hit by COVID-19: data collected by the country’s health authorities show that 99% of people who have died from the disease had at least one chronic condition such as hypertension (76%), type 2 diabetes (36%), coronary heart disease (33%), atrial fibrillation (25%) or cancer (20%).

The impact of these chronic diseases is considerable, with the mortality rate of COVID-19 increasing by 5 to 10 times compared to people who do not have preexisting conditions (Figure 1).

Figure 1. Influence of preexisting chronic conditions on the COVID-19 mortality rate. From: The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team (2020).

People with a chronic condition, including cardiovascular disease, are therefore at much higher risk of developing a severe form of COVID-19, especially if they are older. Consequently, this population must be extra vigilant and avoid interacting with people who may have been in contact with the virus.

Heart damage
In addition to being an important risk factor for COVID-19, cardiovascular disease can also be a consequence of SARS-CoV-2 coronavirus infection. Studies carried out at the beginning of the pandemic observed clinical signs of cardiac injury (elevated blood level of cardiac Troponin I [hs-cTnI], abnormalities of electrocardiograms or cardiac ultrasounds) in 7.2% of infected patients, a proportion that reaches 22% in those affected by severe forms of COVID-19 and who required hospitalization in intensive care. In another study of 138 patients with COVID-19 in Wuhan, 36 patients with severe symptoms treated in intensive care units had significantly higher levels of myocardial injury markers than those not treated in intensive care units. Severe cases of COVID-19 therefore often present complications involving an acute myocardial injury, which seriously complicates the treatment of these patients. It is very likely that these cardiac injuries contribute to the mortality caused by COVID-19, since a study observed hs-cTnI values higher than the 99th percentile (which indicates a myocardial injury) in 46% of patients who had died from the disease, compared to only 1% of survivors. In addition, two recent studies (here and here) have found that the death rate of patients with cardiac injury is much higher than among those without, an increase that can be as high as 10 times in people with a history of cardiovascular disease (Figure 2).


Figure 2. Differences in mortality of patients with COVID-19 depending on the presence of preexisting cardiovascular disease and/or cardiac injury caused by infection. From Guo et al. (2020).

The mechanisms responsible for these heart lesions are very complex and involve several phenomena. On the one hand, poor functioning of the lungs can cause oxygen levels to become insufficient to keep the heart muscle working. This oxygen deficiency is all the more dangerous because the fever caused by the infection increases the body’s metabolism, which increases the workload of the heart. This imbalance between oxygen supply and demand therefore increases the risk of arrhythmia and heart damage.

Another factor involved in heart damage caused by respiratory viruses is what is known as a “cytokine storm”, a phenomenon characterized by an exaggerated inflammatory response following viral infection. The immune system goes berserk and indiscriminately attacks everything in the vicinity, including our own cells, which damages organ function and can increase susceptibility to bacterial infections. The heart is particularly sensitive to this uncontrolled inflammation given its close interaction with the lungs; the oxygenated blood from the lungs reaching the heart has been in direct contact with the foci of infection and therefore necessarily contains a greater concentration of the molecules produced by excess inflammation. When this blood is expelled from the left ventricle to the aorta, a portion of this oxygenated blood is immediately passed to the myocardium to feed the heart cells, with the result that these cells are exposed to abnormally high amounts of inflammatory molecules. An excess of inflammatory molecules can also cause thrombosis (clot formation), which blocks the flow of blood to the heart and causes a heart attack. Indeed, a recent study has shown that high levels of D-dimers, a marker of thrombosis, were associated with a very large increase (18 times) in the risk of mortality from COVID-19.

A clinical study led by Dr. Jean-Claude Tardif, Director of the MHI Research Center, has just been launched to determine whether a reduction in inflammation from viral infection with colchicine, an inexpensive and generally well tolerated anti-inflammatory medication, can prevent the excessive immune response and improve the course of the disease.

It should also be mentioned that in some rare cases, it seems that the heart is the first target of the SARS-CoV-2 virus and that cardiovascular symptoms are the first signs of infection. For example, although the first clinical signs of COVID-19 are usually fever and cough, the National Health Commission of China (NHC) reported that some patients first sought medical attention for heart palpitations and chest tightness rather than respiratory symptoms, but were subsequentlydiagnosed with COVID-19. Recent cases of acute myocarditis caused by COVID-19 in patients with no history of cardiovascular disease have also been recently reported, a phenomenon that had previously been observed for other coronaviruses, including MERS-CoV. A common feature of these viruses is to enter human cells by interacting with the surface protein ACE2 (angiotensin-converting enzyme 2), which is present in large quantities in the lungs, heart and cells of blood vessels. It is therefore possible that the virus uses this receptor to penetrate directly into the cells of the myocardium and cause heart damage. In line with this, it should be noted that analysis of heart tissue from patients who died during the 2002 SARS epidemic revealed the presence of viral genetic material in 35% of the samples. SARS-CoV-2 is very similar (75% identical) to this virus, so it is possible that a similar mechanism is at work.

COVID-19 and hypertension
The interaction of SARS-CoV-2, the virus that causes COVID-19, with the angiotensin-converting enzyme (ACE2) is intriguing, as this enzyme plays a key role in the development of hypertension, and it is precisely hypertensive people who present a more severe form of the infection. Since commonly prescribed antihypertensive drugs cause an increase in the amount of ACE2 on the surface of cells, there have been several texts on social media claiming that these drugs can increase the risk and severity of SARS-CoV-2 infection and should therefore be discontinued. It is important to mention that this hypothesis has no solid scientific basis and that all of the cardiology associations in the world still recommend hypertensive patients continue taking their drugs, whether they are inhibitors of ACE2 (captopril, enalapril, etc.) or angiotensin receptor antagonists (losartan, valsartan, telmisartan, etc.). On the contrary, preclinical studies seem rather to show that antihypertensive drugs could protect against pulmonary complications in patients infected with coronaviruses.

Even a small reduction in caloric intake improves cardiovascular health

Even a small reduction in caloric intake improves cardiovascular health

OVERVIEW

  • 218 healthy and non-obese people were separated into two distinct groups: one control group where people could eat without restrictions and another whose goal was to reduce their caloric intake.
  • For two years, the researchers measured variations in several cardiovascular risk factors, including body weight, cholesterol levels, blood pressure and insulin production.
  • The results show that a reduction of only 12% in caloric intake (or 300 calories per day) is associated with a significant improvement in all of these risk factors and could therefore represent a simple way to reduce the risk of cardiovascular diseases.

A recent report found that in 2016, 60% of the population of Organisation for Economic Co-operation and Development (OECD) countries were overweight, including 25% who were obese. This is huge, and this trend will likely worsen in the coming years due to the dramatic increase in the incidence of overweight among young people: in Canada, for example, the obesity rate among children aged 5 to 19 increased from 2.7% to 12.3% between 1975 and 2016, plus another 20% of children who are considered “pre-obese” and therefore at high risk of obesity. These statistics are alarming because being overweight, and particularly obese, significantly increases the risk of type 2 diabetes, cardiovascular and respiratory diseases, and several types of cancer. According to the OECD, the current situation is likely to reduce Canadian life expectancy by 3 years by 2050 (confirming the pessimistic scenario envisaged a few years ago by some researchers), with catastrophic economic and social repercussions.  

Excess calories
Contrary to popular belief, the high incidence of overweight in the population is not due to lack of exercise. This discourse comes from multinational food companies that seek to promote their high-sugar and high-fat products by suggesting that it is enough to adopt an active lifestyle to counterbalance the caloric intake provided by these products. In fact, studies indicate that it is practically impossible to “burn” the enormous amounts of calories from these processed industrial products and that one therefore cannot compensate for a poor diet simply by being physically active (“you cannot outrun a bad diet,” as the saying goes). In fact, physical activity levels have remained virtually unchanged in the last thirty years in industrialized countries, so a sedentary lifestyle alone cannot explain the phenomenal increase in population waist circumference that has occurred in recent years. Rather, it is the overconsumption of calories, especially those from ultra-processed industrial food, that is largely responsible for the current worldwide obesity epidemic. To avoid gaining extra pounds, the most important thing is to eat less.

Caloric restriction
Several studies suggest that a reduction in caloric intake is associated with several health benefits, especially at the cardiovascular level, as well as an increase in life expectancy. For example, a study of primates (rhesus macaques) showed that a low-calorie diet reduced the incidence of cardiovascular disease in these animals by about half compared to a standard diet. A similar phenomenon has been observed in humans, i.e. people who drastically reduce their caloric intake to about 1200–1900 kcal/day over a 6-year period showed a dramatic improvement in several cardiovascular risk factors (cholesterol, blood pressure, fasting glucose and insulin, inflammation) compared to those who consumed a standard North American diet (2000–3500 kcal/day).

However, this type of severe caloric restriction is very difficult to maintain over long periods of time for most people, and therefore is not really applicable at the population level. In contrast, a recent study suggests that significant improvements in cardiovascular health can also be seen following a much more modest reduction in caloric intake. In this phase 2 clinical study called CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), the researchers randomly separated 218 healthy and non-obese people aged 21 to 50 (BMI between 22 and 28) into two distinct control groups: in one control group, people could eat without any restrictions (ad libitum), and in the other, the objective was to reduce caloric intake by 25%. Over a two-year period, several cardiovascular risk factors were measured in both groups, including blood pressure, cholesterol levels, C-reactive protein (a marker of inflammation), insulin and metabolic syndrome (estimated by combining waist circumference, blood pressure, fasting glucose levels, and triglycerides and HDL cholesterol levels).

Participants’ follow-up shows that the objective of reducing the caloric intake by 25% in the experimental group could not be achieved, with a reduction half as small (12%), which corresponds on average to 279 fewer calories/day at the end of the first year and 216 fewer calories/day after two years. Nevertheless, although relatively modest, this reduction is associated with an average weight loss of 7.5 kg (or 10% of the initial weight) and a significant improvement in all cardiovascular parameters measured in the study (Figure 1). Conversely, the volunteers of the control group gained on average a little weight (0.1 kg) and showed no improvement in these various parameters.

Figure 1. Improvement of several cardiovascular risk factors due to a reduction in caloric intake. From Kraus et al. (2019).

In sum, these results indicate that even in thin and healthy people, a modest reduction in caloric intake (about 300 calories per day, which corresponds to only a slice of pizza) has several positive effects on cardiovascular health. According to the authors, it is likely that these benefits will be even more pronounced in people who are at higher risk of cardiovascular disease due to being overweight. The preventive potential of caloric restriction is therefore immense: according to the OECD report cited earlier, if people in the richest countries, including Canada, reduced their caloric intake by 20%, we could prevent annually 1.1 million cases of cardiovascular disease and save up to $13 billion (USD) each year, a goal that is absolutely impossible to achieve with medication alone.

Saturated fats, coconut oil and cardiovascular disease

Saturated fats, coconut oil and cardiovascular disease

The American Heart Association (AHA) recently published a review of current knowledge on the association between dietary fats and cardiovascular disease. By taking into consideration the entirety of the available scientific evidence, the committee concluded that a lower intake in saturated fat and replacing it with unsaturated fat represents the optimal combination to reduce the incidence of heart disease in the population, especially if it is accompanied by a transition toward an overall healthy diet, such as the Mediterranean diet.

The positive impact of substituting saturated fat with unsaturated fat can mainly by explained by the opposite effects of these two types of fat on the LDL cholesterol level, a well-established risk factor for cardiovascular disease. Whereas saturated fat is associated with an increase of this cholesterol, and thus an increase in the risk of cardiovascular events, unsaturated fat leads to a decrease in LDL cholesterol levels in the blood and is associated with a significant decrease in mortality.  Since animal-based protein sources (meat, dairy products, eggs) are the main sources of saturated fat in diets, whereas plant-based fats are mainly unsaturated, the mere act of reducing consumption of animal products while simultaneously increasing the consumption of plant-based foods is a very easy way to improve the quality of dietary fats, and thus reduce the risk of heart disease. In fact, it is interesting to note that several regions of the world known for their low incidence of cardiovascular disease (Okinawa, Japan; Ikaria, Greece; Sardinia; and the Tsimané people of the Amazon) all share one commonality: a diet high in plant-based foods with a low intake of animal protein and saturated fat.

Plant-based saturated fat
Whereas almost all plant-based fats mainly contain unsaturated fat, there is nevertheless one notable exception: tropical palm and coconut oils (see the Table). Indeed, palm oil (extracted from the fruit pulp) and palm kernel oil (derived from the kernels) contain very high levels of saturated fat (50% for palm oil and 82% for palm kernel oil), which gives them a semi-solid texture at room temperature. This property is used in the food industry to improve the texture of cookies, cakes and other products, and the high level of saturated fat also ensures that these oils are much more resistant to oxidation and considerably improves the shelf life of these foods. However, like all sources of saturated fat, these oils increase blood cholesterol levels and thus are not recommended for cardiovascular health. Not to mention the devastating environmental impact of the intensive cultivation of oil palm, in particular in Indonesia: almost two million hectares of tropical forest are destroyed every year for this crop, a deforestation that has disastrous environmental consequences and threatens animals such as tigers and orangutans from Sumatra and Borneo with extinction.

Table.  Proportion of saturated, monounsaturated and polyunsaturated fat in different animal and plant-based fats.

Source of fatSaturated fat
(g/100g)
Monounsaturated fat
(g/100g)
Polyunsaturated fat
(g/100g)
Butter63264
Canola oil76328
Coconut oil8262
Corn oil132855
Olive oil147310
Palm oil49379
Palm kernel oil82112
Lard394511
Soybean oil162358
Sunflower oil10844

Coconut oil: saturated fat with positive effects?
Coconut oil is another plant-based source that contains a very high proportion of saturated fat (82%), but that, curiously, has gained a good reputation over the years. In fact, a recent survey reported that 72% of Americans consider coconut oil a “healthy” food! Two main characteristics of coconut oil, frequently mentioned in mainstream press, explain this popularity:

1) Population studies. Epidemiological studies conducted among populations that consume large quantities of coconut, such as the inhabitants of Polynesian islands like Tokelau or those of the Melanesian island Kitava, revealed a low incidence of heart disease, despite a high intake of saturated fat from this fruit. It should be noted, however, that it is the coconut meat, very high in fibre, that is consumed by these populations, so the lack of effect on cardiovascular disease cannot be extrapolated to that associated with adding purified coconut oil to Western diets, which contain a large proportion of processed foods.

2) Impact on cholesterol. The saturated fat in coconut oil has shorter chains than that found in palm oil or in butter, and, in theory, has less harmful effects on cholesterol levels. About half of saturated fat contained in coconut oil is in the form of lauric acid (12 carbon atoms), and studies show that the effect of this fatty acid on LDL cholesterol is half that of palmitic acid (16 carbon atoms). In practice, however, a systematic review of the studies conducted to date indicates that coconut oil increases LDL cholesterol levels in a similar way to other sources of saturated fat (butter, palm oil) and in a more significant way than unsaturated fat, such as olive oil for example.

Overall, these observations suggest that coconut oil is a source of saturated fat like any other, and that it should be used sparingly to prevent an increase in the risk of heart disease. For everyday cooking, virgin olive oil is a much better choice because of its very well documented positive effects on cardiovascular health. Among other plant-based oils, the use of canola oil is recommended, as it contains the highest proportion of omega-3 polyunsaturated fats, known for their anti-inflammatory effects.

Type 2 diabetes can be cured

Type 2 diabetes can be cured

Type 2 diabetes is without question one of the most serious consequences of being overweight. With the steady increase in obesity worldwide, the International Diabetes Federation estimates that 415 million adults have diabetes, and that 318 million are “pre-diabetic,” i.e., have chronic glucose intolerance, which puts them at high risk of eventually developing the disease. This is a major concern, as diabetes causes premature aging of the blood vessels and significantly increases the risk of cardiovascular disease.

Type 2 diabetes is generally considered to be a chronic, irreversible and incurable disease, for which the only therapeutic option is to limit the damage caused by hyperglycemia. In this testimonial, Normand Mousseau, Professor of Physics at Université de Montréal, demonstrates that this is not the case, and that drastic lifestyle changes leading to significant weight loss may be sufficient to restore blood glucose levels and to completely eliminate diabetes without medical or pharmacological intervention. This is a spectacular example of the immense potential of lifestyle to not only prevent but also cure certain diseases resulting from being overweight. 

I was diagnosed with type 2 diabetes four years ago, in May 2013. Seeking treatment for an infection that would not heal, I consulted a doctor. I was 46, I didn’t have a family physician and hadn’t had a medical examination in a long time. Indeed, despite being very overweight – at the time, I weighed 230 pounds (104 kg) at 5’11” (180 cm) – I thought I was in good health.

A few days after the blood test recommended by my doctor, he gave me the bad news: my fasting blood sugar exceeded 14 mmol/l, double the threshold for diabetes. When I asked him what I could do to heal, he replied that type 2 diabetes is a chronic and degenerative disease. All I could do was slow its progression and limit its effects by combining medication with weight loss, better nutrition, and a little physical exercise.

The news hit me hard: type 2 diabetes is a terrible and insidious disease that affects quality of life, and even causes death.

As soon as I was diagnosed, I decided to change my lifestyle. While taking 500 then 850 mg of metformin twice a day, I cut sugar, added a lot of vegetables to my diet, and started running. I also learned to use a blood glucose meter to monitor the daily fluctuations in my blood sugar, in constant fear that it might exceed acceptable thresholds.

As a result of these lifestyle changes, I quite rapidly lost about 30 pounds. By the end of 2013, I was running 5 to 7 km two or three times a week and weighed around 195 pounds. My diabetes was still there, however, as was the certainty that the disease would progress and that all of my efforts would be in vain.

Finally, almost a year after my diagnosis, in April 2014, I decided to redouble my efforts and checked for myself whether type 2 diabetes was really a chronic disease. After a few days of research in medical journals and on the Internet, among the false promises and half-truths, I found news that seemed credible and confirmed that yes, type 2 diabetes can be cured!

The treatment proposed by Professor Roy Taylor of Lancaster University in the United Kingdom is alarmingly simple: you have to lose weight, usually a lot, and probably quickly.

Taylor’s approach is based on three sets of results, some of which date back more than 50 years:

  • First, it has been known since the mid-1970s that a large percentage of people with type 2 diabetes who undergo bariatric surgery to reduce stomach size and facilitate weight loss recover from diabetes, so the disease is not irreversible;
  • Second, it has been known for about 20 years that the beta cells of the pancreas, which are responsible for the production of insulin, are very sensitive to the presence of fat molecules;
  • Finally, thanks to magnetic imaging, it has been observed that, even in a group of people with a healthy weight, some individuals with diabetes show an above-average presence of fat in their internal organs.

Based on this work, Taylor concluded that the presence of fat in internal organs is toxic to the pancreas, and that reducing it can allow the organ to function normally again. He then developed an approach that he tested on 13 diabetic and overweight individuals: for two months, they adopted a very low-calorie diet of 600 to 700 calories a day. Despite the small study size, the results, published in 2011, are staggering: the majority of participants reached blood glucose levels below the diabetes threshold and maintained normal blood glucose levels for three months after the end of the study. In a journal article published shortly afterwards, Taylor stated that his approach also worked for people on insulin.

I was astounded when I read this research. Could the solution be that simple?

Since I had little to lose by testing the approach, except for a little weight, I started on a very low-calorie diet, adopting an alternating two-phase approach:

  • a 600-calorie diet for 8 to 10 days, eating a minimum of 200 g of vegetables, and drinking 2 litres of water a day
  • three weeks on a more reasonable 1,500-calorie diet.

By the end of my third 600-calorie round in August 2014, I weighed 165 pounds, had lost about 30 pounds, and was completely cured, with fasting blood glucose levels of about 5.8 mmol/l, without any medication. One year later, in October 2015, my weight had stabilized around 170 pounds, my HbA1c was 5.1%, and my blood sugar was 5.7 mmol/l.

Almost three years after the end of my treatment, I am eating normally while monitoring my weight, I run 8 to 10 km 3 times a week, and I maintain my fasting blood sugar levels around 5.7 mmol/l. Of course, I am still at risk of developing type 2 diabetes – my genetic predisposition hasn’t disappeared! – and if I regain the weight, it is very likely that after some time my pancreas will start to fail again. However, I am no longer diabetic, and that is a great relief.

Since the publication of my book last year, I’ve received many testimonials from people of all ages reporting their success in beating their type 2 diabetes by following this diet. Some of them shared that their doctors were simply amazed. All of them told me that their lives had been changed as a result.

Despite its simplicity, this treatment isn’t easy: losing weight demands significant effort; keeping it off requires iron will and a profound lifestyle change. However, it is worth the effort, as type 2 diabetes is a devastating disease that greatly reduces our quality of life. So, there is no reason not to start today!

Normand Mousseau
Professor of Physics, Université de Montréal

Author of the book “Comment se débarrasser du diabète de type 2 sans chirurgie ni médicament”, Éditions du Boréal (2016). [available in French only]

References:
Lim, E. L., K. G. Hollingsworth, B. S. Aribisala, M. J. Chen, J. C. Mathers and R. Taylor (2011). “Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol.” Diabetologia 54(10): 2506-2514.

Taylor, R. (2013). “Banting Memorial lecture 2012: reversing the twin cycles of type 2 diabetes.” Diabet Med 30(3): 267-275.

Tham, C. J., N. Howes and C. W. le Roux (2014). “The role of bariatric surgery in the treatment of diabetes.” Therapeutic Advances in Chronic Disease T5: 149-157.