Metabolic Syndrome: a Complex Issue With Socioeconomic Burden

Despite increased awareness of the importance of a healthy lifestyle and advances in medical and pharmacological treatments, metabolic syndrome is still a big problem for society and the economy. Metabolic syndrome is a complex set of metabolic disorders that are influenced by both genetics and lifestyle choices, including a sedentary lifestyle and an unbalanced diet, especially in adults. Another hurdle in tackling metabolic syndrome is the need for more agreement on how to define it and what the diagnostic criteria should be.

Metabolic Syndrome, however, is characterised by several risk factors, including high blood pressure, abdominal obesity, insulin resistance, unhealthy cholesterol levels and a pro-thrombotic and pro-inflammatory state. These risk factors are all connected and each one makes the others worse. This dangerous combination significantly increases the risk of chronic diseases, including type 2 diabetes and cardiovascular disease.

From Syndrome X to Metabolic Syndrome

In 1988, Dr. Gerald Reaven introduced the world to a perplexing medical mystery called “syndrome X.” His groundbreaking observation linked insulin resistance to a cluster of abnormalities that paved the way for type 2 diabetes and cardiovascular diseases (1). As this condition gained attention, it was renamed “metabolic syndrome” (MetS) to distinguish it from the previously established cardiac syndrome X (2). 

It is important to note that MetS is not a disease itself. Rather, more strictly speaking, it is a term used to describe a complex condition that includes several key factors. These include insulin resistance, a condition where the body’s cells become less responsive to insulin, leading to elevated blood sugar levels; hyperinsulinemia, where the levels of insulin in the blood are high; dysglycemia, accompanied by excessive blood glucose levels and finally dyslipidemia, a condition characterised by abnormal levels of lipids in the blood, such as cholesterol and triglycerides. Additionally, high blood pressure is often associated with this condition. 

Diagnosing MetS involves piecing together a puzzle of six critical indices: waist circumference, blood pressure, fasting glucose level, triglycerides, cholesterol, and high-density lipoprotein (HDL) levels (2, 3). Individuals with an “apple-shaped” body are at a higher risk of developing insulin resistance than those with a “pear-shaped” body (4, 5). Nevertheless, waist circumference is not a good indicator for a comprehensive picture of abdominal obesity. Indeed, it needs to be evaluated alongside body mass index (BMI). In addition, excess visceral fat is often linked to non-alcoholic fatty liver disease (NAFLD), where fat infiltrates liver cells, potentially leading to cirrhosis or liver cancer (6).  

A Silent Epidemic with Health and Financial Implications

The global prevalence of metabolic syndrome is astonishing, affecting approximately 20-25% of adults (7). This silent epidemic is spreading fastest in the urban populations of developing countries, with notable increases in the United States and Europe (8, 9). Individuals with MetS face a doubled risk of mortality and a tripled risk of myocardial infarction or stroke compared to those without the condition (7). Even more alarming, they are five times more likely to develop type 2 diabetes mellitus (T2DM)(10). In 2019, the estimated total number of cases of T2DM was 43.8 million, while the estimated total number of cases of hypertension (HTN) was 18.5 million (11).

These numbers represent more than just statistics, they are a reflection of the growing epidemic of metabolic diseases that has steadily worsened over the past two decades. From 2000 to 2019, deaths from these conditions showed a relentless upward trend. Obesity emerged as the most significant killer, responsible for 5.0 million deaths in 2019 alone, followed by deaths due to hyperlipidemia (HLD), a condition marked by high levels of fats in the blood, which claimed 4.3 million lives. T2DM accounted for 1.4 million fatalities, HTN for 1.1 million and NAFLD for 168,969 deaths (11). The prevalence of these metabolic diseases increased across the board, with the most significant spikes observed in countries with a high socio-demographic index. 

A study by Boudreau and colleagues found that people with metabolic syndrome had higher costs compared to those without the condition (12). Indeed, it is shown that the average annual total costs between subjects with metabolic syndrome and those without differed significantly, at a magnitude of 1.6 overall ($5,732 vs. $3,581) and 1.3 when stratified by diabetes (diabetes, $7,896 vs. $6,038; no diabetes, $4,476 vs. $3,422). On average, total costs increased by 24% for each additional risk factor. Subjects with diabetes and weight risk, dyslipidaemia and hypertension incurred costs that were almost double those of subjects with prediabetes and similar risk factors ($8,067 vs. $4,638)(12).

From Underlying Causes to Effective Management

The pathophysiology of MetS is a complex issue that requires a thorough understanding. Scientists and doctors are still debating whether the various elements of MetS represent distinct pathologies or are part of a broader, interconnected process. At the heart of this debate lies a mix of genetic, epigenetic—changes in gene expression that do not alter the DNA sequence—lifestyle and environmental factors (13). Overeating and inactivity have been identified as significant contributors to the development of MetS.

High caloric intake, coupled with visceral adiposity—excess fat around the internal organs—serves as a primary catalyst for numerous pathways associated with the syndrome (14, 15). Three main mechanisms have been proposed to explain how MetS progresses and ultimately leads to cardiovascular diseases and T2DM. These are insulin resistance, chronic inflammation—an ongoing, low-grade inflammatory state that wreaks havoc on the body, and neurohormonal activation—a complex interplay of nervous and hormonal signals that can exacerbate MetS (16, 17, 18).

Managing metabolic syndrome (MetS) is like navigating a labyrinth, but emerging research offers several guiding lights. The most effective strategy? Embracing an active lifestyle paired with a nutritionally balanced diet. In this scenario, the Mediterranean diet, a time-honoured nutritional approach, is proving to be a powerful ally against MetS (19, 20). Picture the sunny Mediterranean, full of tasty food like olive oil, fish, cereals, vegetables, and fruits. These components aren’t just delicious—they’re packed with antioxidant and anti-inflammatory properties (21, 22).

A comprehensive meta-analysis by Salas-Salvadó and colleagues, reviewing 50 prospective studies and randomized control trials, found that greater adherence to the Mediterranean diet significantly reverses the metabolic syndrome and its components (23). Beyond dietary changes, a range of other strategies can help manage MetS. Natural substances like nutraceuticals, butyrate, probiotics, coconut oil, and curcumin are gaining attention for their potential benefits (24). In the pharmaceutical area, statins and anti-hyperglycemic agents are commonly used to tackle the syndrome’s underlying issues.

Looking Ahead

Metabolic syndrome is a complex condition that presents a significant risk of heart disease and type 2 diabetes. It is characterised by a combination of interrelated components and risk factors. This condition, which is complex and poorly understood, has prompted extensive research efforts to identify its underlying mechanisms and develop effective treatments.

While the most effective treatment for metabolic syndrome remains to be seen, scientists are actively pursuing new avenues of research along its intricate pathways. They are seeking biomarkers that could serve as early warning signs, enabling the syndrome to be identified and treated before it progresses. Among the current strategies, efforts to tackle excess body fat and insulin resistance show promise in achieving broader success. These strategies represent crucial fronts in the fight against metabolic syndrome, to reduce its adverse effects on health.

Despite notable advancements in recent years, there is still much to be done to fully understand metabolic syndrome. Researchers are focusing their efforts on unravelling the links between metabolic syndrome and other conditions, including non-alcoholic fatty liver disease, sleep disorders, reproductive tract issues and microvascular diseases.

As the quest for answers continues, each discovery brings us closer to comprehending this multifaceted condition and potentially transforming outcomes for those affected. The future of metabolic syndrome treatment hinges on ongoing exploration and collaboration across scientific disciplines, driven by the urgency to improve health outcomes worldwide.

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