Metabolic syndrome: what it is, why it happens and how it is managed

Perhaps a blood test report mentioned metabolic syndrome and you were left wondering whether it is a disease, a warning sign or simply a label. The honest answer is that it is not a single disease: it is a cluster of risk factors of metabolic origin (abdominal obesity, abnormal blood fats, raised blood glucose and high blood pressure) that occur together more often than chance would predict. In fact, whether it exists as a distinct entity in its own right remains a matter of debate among specialists. Here we explain what we know, what its criteria mean and what the evidence says about reducing the risk, without scaremongering and without promising shortcuts.

What metabolic syndrome actually is

The idea was born in 1988, when Reaven described what he called Syndrome X: the tendency of hypertension, impaired glucose tolerance, raised triglycerides and low HDL cholesterol to appear together. Over time that clustering was attributed to insulin resistance (hence it was also called insulin resistance syndrome), and the World Health Organization eventually renamed it metabolic syndrome. Insulin resistance is regarded as the central mechanism: the body produces insulin, but the cells respond less well than they should.

That is why it is best understood as a risk map rather than as the diagnosis of one specific disease. Having metabolic syndrome does not mean you are ill with a particular condition; it means you have several signals that, taken together, point to a higher cardiovascular and metabolic risk.

The 5 criteria: how it is defined

For years there were competing definitions. The IDF definition required abdominal obesity as a prerequisite and used different cut-off points depending on geography; the NCEP definition did not require it and applied a single set of thresholds, so the syndrome could be diagnosed on other criteria. In 2009 a harmonised definition was agreed that settled much of the debate: abdominal obesity is no longer a mandatory requirement and becomes one of the five criteria, of which meeting three is enough for the diagnosis.

• Raised waist circumference (abdominal obesity).
• Raised triglycerides.
• Low HDL cholesterol.
• Raised blood pressure.
• Raised fasting blood glucose.

On waist circumference, the IDF recommendation for people of European origin sets the threshold at 94 cm or more in men and 80 cm or more in women. It is an easy measurement to take at home with a tape measure, although interpreting it is always a matter for a healthcare professional within each person's own context.

Why it happens: inflammation, clotting and fat tissue

Metabolic syndrome is not just about sugar and fats. It is associated with prothrombotic and proinflammatory states, that is, with a greater tendency towards clotting and low-grade inflammation. Increases are seen in plasminogen activator inhibitor (PAI-1) and fibrinogen, both linked to clotting. And fat tissue is not a passive store: it releases mediators such as free fatty acids, adiponectin, interleukin 6, resistin, leptin and TNF-alpha, which connect adiposity with insulin resistance. That is the thread linking excess abdominal fat with all the other abnormalities.

How common it is in Spain

To get a sense of the scale of the problem in this country, the DARIOS study analysed pooled individual data from 11 studies, covering 24,670 people from 10 autonomous communities aged 35 to 74. The prevalence of metabolic syndrome was 31% (women 29%, 95% CI 25-33%; men 32%, 95% CI 29-35%). This is not a minority issue: almost one in three adults in that age range met the criteria.

There are also differences between the sexes. Raised blood glucose and raised triglycerides were more common in men, while abdominal obesity and low HDL cholesterol predominated in women. It is worth bearing in mind that prevalence varies considerably depending on the definition used, the age range, the population studied and when the analysis was carried out: that is why figures differ so much from one study to another. In Spanish patients with type 2 diabetes, for example, prevalence ranged from 71.5% using WHO criteria to 78.2% with NCEP-ATP III criteria and 89.5% with IDF criteria.

How it is managed: what the evidence says

The important question is what can be done. And here the strongest evidence does not come from a tablet, but from a change in habits. The Diabetes Prevention Program randomly assigned 3,234 non-diabetic people with raised blood glucose to three groups: placebo, metformin (850 mg twice a day) or an intensive lifestyle programme aiming to lose at least 7% of body weight and do 150 minutes or more of physical activity a week.

The results were clear. The incidence of diabetes fell by 58% with the lifestyle intervention and by 31% with metformin, compared with placebo. In absolute terms, the incidence was 11.0 cases per 100 person-years on placebo, 7.8 with metformin and 4.8 with lifestyle change. The number needed to treat to prevent one case of diabetes was 6.9 with lifestyle change and 13.9 with metformin. Put another way: fewer people had to be supported through changes in habits to prevent one case than had to be treated with the drug.

The effect persisted in the long term, although in a more muted form. Over the 10 years of combined follow-up in the DPP and its DPPOS extension, the incidence of diabetes was reduced by 34% in the lifestyle group and by 18% in the metformin group compared with placebo. One honest caveat: when these prevention studies examined the impact of their interventions on cardiovascular risk, no clear benefit emerged, except for acarbose, and that finding was not subsequently confirmed.

The role of metformin, without the myths

It is worth being precise here, because there is a widespread idea that metformin is used to treat metabolic syndrome or prediabetes. In Spain its authorised summary of product characteristics covers the treatment of type 2 diabetes mellitus, particularly in people who are overweight when diet and exercise are not enough, either as monotherapy or combined with other antidiabetic drugs or insulin. In children and adolescents it also requires the diagnosis of type 2 diabetes to be confirmed before starting treatment, and the summary of product characteristics does NOT include metabolic syndrome or prediabetes as authorised indications.

That does not mean metformin is irrelevant in a metabolic context: according to its summary of product characteristics, at therapeutic doses it has favourable effects on lipid metabolism, reducing total cholesterol, LDL and triglycerides, independently of its action on glucose. But any decision about using it rests with a doctor after assessing the individual case, and it is not free of precautions: its contraindications include hypersensitivity, acute metabolic acidosis, diabetic pre-coma and severe kidney failure, with a glomerular filtration rate below 30 ml/min.

In summary

The take-home message: metabolic syndrome is a set of risk signals, not a definitive label, and the firmest evidence for reducing that risk comes down to habits, which in these studies outperformed medication in preventing diabetes. If you recognise yourself in these signals and want to understand your situation properly, what exists in Spain today is medical weight-loss treatment, with prior assessment, a prescription where appropriate from a registered doctor and ongoing follow-up. The first step is knowing where you stand: you can check whether you are eligible.