Halting the march of metabolic syndrome

In medical lexicon ‘metabolic syndrome’ (MetS) might not exactly trip from the tongue like ‘heart disease’ or ‘cancer’.  Yet, depending on where you live in the world, there could be a one-in-three chance you have the condition already.  And despite its relative obscurity, be in no doubt: its impact is life threatening.

One recent study showed a dramatic rise in MetS prevalence within the United States between 2011 and 2016, from 32.5% to 36.9% of the population.[1]  That’s almost a 5% rise in as many years – a shocking figure, and one that encompasses nearly half of all people in the 60+ age bracket.

Age-specific prevalence of metabolic syndrome in United States

Worse, MetS can lead to fatal outcomes such as heart attacks and strokes for those affected.

Given the prevalence of MetS, its deadly ramifications, and its absence from the public vernacular, we owe it to ourselves to find out more about this condition.  If we understand what it is, so the theory goes, we stand a better chance of halting its merciless rise.

To begin getting our heads around the issue, let’s stop thinking of MetS as ‘just one thing’.  It’s more complex than that – imagine instead a confluence of malfunctions relating to the body’s energy assimilation and transfer systems.  Together, these traits represent a health challenge far greater than the sum of their parts.

MetS – what it means for mortality

From a medical perspective, a patient is deemed to have MetS if three or more specific symptoms are observed.

• Firstly, obesity.  For the purposes of diagnosing MetS, this means a waistline of 40+ inches in men or 35+ inches in women, or a body mass index (BMI) of 30 or over.
• Hypertension or high blood pressure, deemed anything above 85 mmHg (resting pressure) or 130 mmHg (pumping pressure), is another indicator.
• A further consideration is high blood sugar, interpreted as a fasting plasma glucose level of 100 mg/dL or above.
• Another warning sign is low levels of HDL cholesterol (high-density lipoprotein – the helpful kind), under 50 mg/dL in women or 40 mg/dL in men.
• Finally, patients with suspected MetS might be tested for high ‘blood fat’ levels (known as triglycerides) of 150 mg/dL and above.

Check three or more of these boxes and, you are probably the newest member of the MetS club – a fast-growing club that no one should want to join.

MetS presents a uniquely dangerous combination of health risks which together increase the likelihood of experiencing life-changing medical events: suffering strokes and heart attacks, developing diabetes, acquiring kidney and liver disease, or even falling foul of sleep apnea, a potentially serious condition manifesting in nighttime breathlessness and gasping.

Evidence of MetS surrounds us, both in our homes and in our hospital wards.  Globally, some 550 million people are living with heart and circulatory diseases, currently accounting for around 18 million deaths per year.^[2]  Diabetes and kidney disease, meanwhile, are estimated to cause around 2 million deaths annually.^[3]

Collectively, the health problems associated with MetS equate to an approximately 1.6-fold increase in mortality.[4]  That’s a serious prognosis.

As with many global health emergencies there is little that is ‘fair’ about MetS, and already we see it spreading disproportionately among particular sections of society.  Often those who are least able to cope.

MetS becoming a global phenomenon

The figures above that demonstrate the rising incidence of MetS in the US show only a partial picture.  A more subtle breakdown helps shine a light on particular at-risk groups.

Research shows that during the five-year period 2011 to 2016, MetS cases rose fastest among women (31.7% to 36.6%), people aged 20-39 (16.2% to 21.3%), Hispanic adults (32.9% to 40.4%) and Asian adults (19.9% to 26.2%).^[5]  Social and environmental factors are figured to account for some of the ethnic variants, and rates emerged as roughly even between the genders – but age clearly matters.  Just one in five young adults have MetS, compared to almost half of those in the 60+ age bracket.

Looking deeper, more clues emerge.  Another recent study, synthesizing data sets from around the world, reveals MetS as a truly global phenomenon.  Furthermore, it shows that demographic disparities occur, albeit unevenly, across multiple regions.[6]

In China, 9.8% of males and 17.8% of females aged 35 to 74 are currently diagnosed with MetS.  So too are 17.1% of men and 19.4% of women aged over 20 in India.  This compares to 33.7% of men and 35.4% of women aged 20 and above in the United States.  In Denmark, 18.6% of men and 14.6% of women aged from 41 to 72 are classed as suffering from MetS.  In South Korea, it is 5.2% of men and 9.05% of women aged 20 to 28.  And in Australia, MetS in the 25+ age range was noted in 24.4% of men and 19.9% of women.

Evidently, there is no single factor governing MetS’ prevalence.  In gender terms, women are more likely than men to suffer from MetS in countries such as the US or China, but the opposite is true in countries such as Denmark or Australia.

Clearly, we must look deeper to identify why MetS is on the march globally.

While an official genetic definition of MetS remains elusive, researchers have established that its differing components co-exist more frequently than would be expected by sheer chance – confirming its status as a definable condition.

Furthermore, its symptoms also indicate a degree of heritability.  Having a close relative with MetS increases one’s chances of developing the same condition by 24%.  Depending on the study chosen, familial ties increase individual risk factors by varying amounts: high blood pressure by 20%, obesity by 44%, and irregular cholesterol by 54%.[7]

Beyond these correlations, where else can we look for causal factors?  Most likely, we should examine lifestyle.

Getting under the skin of a weighty problem

The chief culprit in the rising cases of MetS worldwide appears to be a tendency towards expanding waistlines.  Back in 2005, the World Health Organization (WHO) calculated that around one billion people globally were overweight.  A decade later, the number of people classed as overweight reached 1.5 billion.[8]  By 2021, the WHO estimated that almost 40% of adults globally were overweight, including more than 340 million children and adolescents.[9]

The causes of this health crisis are twofold: an increase in the consumption of high fat, high sugar foodstuffs and drinks; and a decrease in physical activity due to growing urbanization and more machine labor.

Where is the obesity capital of the world?  America.

The Centers for Disease Control and Prevention (CDC), the US national public health agency, revealed that obesity in the country had reached an unprecedented prevalence of four-in-ten people by March 2020, up from three-in-ten 20 years earlier.[10]

Look again at those figures for the incidence of MetS in the USA: 33.7% of men and 35.4% of women – numbers that simply dwarf the rates in most countries across Asia and Europe.

Once again, America establishes itself as a global leader – only not in an enviable manner.

The correlation between rising obesity and surging MetS is so stark it cannot be ignored.  Here, then, we identify weight as the major ‘smoking gun’ for the development of MetS – and our best clue towards identifying a solution.

Fats, salts and carbs: A passport to MetS

On the basis that prevention is better than cure, solving the scourge of MetS will primarily mean tackling the world’s diet and obesity crisis.

Simply put, we eat too much of the wrong foods and we prioritize speed and convenience over health.  Naturally, there is a steep price to pay whenever we step on the scales.

India, one of the world’s diabetes hotspots with around 73 million cases, faces separate challenges.  By some estimates, one-third of Indian adults display a degree of MetS.[12]  Around 70% of calories in India come from poor-quality carbohydrates such as flour-based products, starchy snacks, white rice and bread.  The average Indian also consumes three to four times as much sugar as the WHO recommends.

Compare this to the picture in South Korea, which has a notably low incidence of MetS, with just 5.2% of men and 9.05% of women aged 20 to 28 affected.  South Korea has some of the lowest obesity rates in the world and, unsurprisingly, a diet rich in high-protein, low-calorie foods such as kimchi, soups, seafood and steamed vegetables.

As they say, you are what you eat.  While taking more exercise can certainly help ward off MetS, experts believe the single most beneficial lifestyle change would be adopting a more gut-friendly diet.[13]

What would this mean for dinner plates globally?

• More protein from fish and poultry in place of red meat
• Olive oil as the chief fat source
• More plant-based foods, grains, nuts and legumes
• Fresh fruit for pudding instead of processed desserts
• Fewer sweets and other products containing refined sugars
• Less alcohol overall

Such a diet can help normalize weight, blood pressure, cholesterol and blood sugar levels, reducing overnight the incidence of coronary disease and diabetes.

It’s a strategy supported by the science.  One study, focusing on people of Hispanic origin in the US, showed that weight loss of at least 5% of body weight, along with increased physical activity, were the most effective preventions for MetS.[14]

Where prevention falls short, medications exist that can help regulate cholesterol, blood pressure and sugar levels.  Statins and ezetimibe are frequently used to improve patients’ lipid (cholesterol and triglycerides) profiles.  Relatively new drugs including thiazolidinediones, GLP-1 agonists and DPP-4 inhibitors can further help reduce the progression of MetS.^[15]

In a fairer, more medically-democratic world, these treatments could be rolled-out universally, offering relief from this life-limiting condition irrespective of people’s nationality or income level.  While there is no magic bullet solution for current disparities in medical interventions worldwide, the private sector is emerging as a key weapon in the drive to improve health outcomes in developing societies.

Tackling MetS from a global perspective

MetS is now firmly established as a significant, and growing, socioeconomic problem throughout the world.[16]

MetS, as a prime cause of coronary disease, diabetes and cancer, not only claims lives – it also reduces healthy life expectancy (HLE), the phase of life when one can be a productive member of society, contributing to GDP and paying taxes.  Managing the symptoms of MetS, conversely, is punishingly expensive.  In the US alone, treating diabetes costs around US$ 250 billion annually, and heart disease a further US$ 100+ billion.

Going forward, to truly confront the menace of MetS, we must collect more standardized data from a wider range of countries and agree upon a globally-acceptable threshold for MetS diagnosis.

With public sector finances currently battered by the dual pressures of COVID-19 recovery and the impacts of the conflict in Ukraine, focus turns to the private sector to try and navigate society to a more equitable health ecosystem.

After all, private capital, its focus immune from the shifting whims of shareholders and policymakers, can make the kind of long-term decisions that inspire lasting cultural and institutional change.

Our team at Abdul Latif Jameel Health is dedicated to driving health inclusivity through accelerating access to modern medical care, particularly across the developing Global South.  In collaboration with world-leading partners, we aim to find innovative solutions to advance the future of health technology.

Some of these partnerships illustrate the scope of our vision and ambition.  For instance, we have teamed up with Evelo Biosciences to help develop therapeutic medicines centered on the small intestine – medicines governing the metabolic, neurological and immune systems.

Our work with fellow US-based drug tech EQRx, meanwhile, will help bring to market its affordable tumor-fighting drugs. EQRx’s growing portfolio of medicines in development is targeting diseases and therapeutic classes that create a high cost burden to patients and society

Then there is our collaboration with US biotech Laronde, pursuing a novel way of modulating human biology via ‘Endless RNA’ (eRNA).  Such uniquely engineered RNA can be programmed to express diverse therapeutic proteins inside the body.

With these partnerships, and others like them, we aim to level-up access to healthcare in key markets across the world.

As global health challenges continue to mount, we must begin tackling the MetS problem from both prevention and cure perspectives.  We must equip people with the necessary lifestyle guidance to avoid the pitfalls of MetS, while hastening the next generation of breakthrough treatments to counter the constellation of health problems which follow in the wake of diagnosis.

Few people may yet be familiar with the phrase ‘metabolic syndrome’ – but with an ageing population and declining quality of diets worldwide, blissful ignorance is a luxury we cannot afford for much longer.

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[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312413/

[2] https://www.bhf.org.uk/-/media/files/research/heart-statistics/bhf-cvd-statistics-global-factsheet.pdf

[3] https://www.who.int/news-room/fact-sheets/detail/diabetes

[4] https://onlinelibrary.wiley.com/doi/epdf/10.1111/obr.12229

[5] https://www.health.harvard.edu/blog/metabolic-syndrome-is-on-the-rise-what-it-is-and-why-it-matters-2020071720621

[6] https://onlinelibrary.wiley.com/doi/epdf/10.1111/obr.12229

[7] https://onlinelibrary.wiley.com/doi/epdf/10.1111/obr.12229

[8] https://onlinelibrary.wiley.com/doi/epdf/10.1111/obr.12229

[9] https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

[10] https://www.cdc.gov/obesity/data/adult.html

[11] https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/western-diets

[12] https://timesofindia.indiatimes.com/life-style/health-fitness/diet/what-is-wrong-with-the-indian-diet-apparently-a-lot-claims-uk-based-cardiologist-dr-aseem-malhotra/articleshow/75742419.cms

[13] https://www.health.harvard.edu/blog/a-practical-guide-to-the-mediterranean-diet-2019032116194

[14] https://www.dovepress.com/a-high-incidence-of-metabolic-syndrome-traits-in-mexicans-points-at-ob-peer-reviewed-fulltext-article-DMSO

[15] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304358/

[16] https://onlinelibrary.wiley.com/doi/epdf/10.1111/obr.12229