Metabolic syndrome
Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein.
Metabolic syndrome is associated with the risk of developing cardiovascular disease and type 2 diabetes. In the U.S., about 25% of the adult population has metabolic syndrome, a proportion increasing with age, particularly among racial and ethnic minorities.
Insulin resistance, metabolic syndrome, and prediabetes are closely related to one another and have overlapping aspects. The syndrome is thought to be caused by an underlying disorder of energy utilization and storage, but the cause of the syndrome is an area of ongoing medical research. Researchers debate whether a diagnosis of metabolic syndrome implies differential treatment or increases risk of cardiovascular disease beyond what is suggested by the sum of its individual components.
Signs and symptoms
The key sign of metabolic syndrome is central obesity, also known as visceral, male-pattern or apple-shaped adiposity. It is characterized by adipose tissue accumulation predominantly around the waist and trunk. Other signs of metabolic syndrome include high blood pressure, decreased fasting serum HDL cholesterol, elevated fasting serum triglyceride level, impaired fasting glucose, insulin resistance, or prediabetes. Associated conditions include hyperuricemia; fatty liver progressing to nonalcoholic fatty liver disease; polycystic ovarian syndrome in women and erectile dysfunction in men; and acanthosis nigricans.Neck circumference
Neck circumference has been used as a simple surrogate index of upper-body subcutaneous fat. Values > and > are considered high risk for metabolic syndrome, and large neck circumference more than doubles risk. In adults with overweight/obesity, clinically significant weight loss may protect against COVID-19, and neck circumference has been associated with increased risk of mechanical ventilation and mortality in hospitalized COVID-19 patients.Complications
Metabolic syndrome can lead to type 2 diabetes, cardiovascular diseases, stroke, kidney disease and nonalcoholic fatty liver disease. It is also associated with a significantly increased risk of surgical complications across most types of surgery in a 2023 systematic review and meta-analysis of >13 million individuals.Causes
The mechanisms underlying metabolic syndrome are under investigation and only partially elucidated. Most affected people are older, obese, sedentary, and have some degree of insulin resistance. Stress can also contribute. Important risk factors include diet, genetics, aging, sedentary behaviour or low physical activity, disrupted chronobiology/sleep, mood disorders and some medications, and excessive alcohol use. The pathogenic role of excessive adipose expansion under sustained overeating and resulting lipotoxicity has also been proposed.Markers of systemic inflammation including C-reactive protein, fibrinogen, interleukin 6, and tumor necrosis factor-alpha are often increased. Some research has focused on increased uric acid levels from dietary fructose.
Modern "Western diet" patterns with high intake of energy-dense processed foods are a factor in the development of metabolic syndrome. Rather than total adiposity, the core clinical component is visceral/ectopic fat, and the principal metabolic abnormality is insulin resistance. A chronic energy surplus unmatched by activity may lead to mitochondrial dysfunction and insulin resistance.
Stress
Prolonged chronic stress may contribute to metabolic syndrome via dysregulation of the hypothalamic–pituitary–adrenal axis. Elevated cortisol can raise glucose and insulin levels, promoting visceral adiposity, insulin resistance, dyslipidaemia, and hypertension, and has effects on bone turnover.Pathophysiology
It is common for there to be a development of visceral fat, after which adipocytes increase plasma levels of TNF-α and alter levels of other adipokines. TNF-α can induce inflammatory cytokines and may trigger insulin resistance. Rat models with high-sucrose diets have shown progression from hypertriglyceridaemia to visceral fat accumulation and insulin resistance. Increased adipose tissue elevates immune cells and chronic inflammation, contributing to hypertension, atherosclerosis and diabetes.The endocannabinoid system may contribute to metabolic dysregulation. Overproduction can alter reward circuitry and executive function, perpetuating unhealthy behaviours. The brain modulates peripheral carbohydrate and lipid metabolism. Overfeeding with sucrose/fructose, particularly with high-fat intake, can induce features of metabolic syndrome in animals. Arachidonic acid–derived mediators may link lipid oversupply and inflammation.
Diagnosis
NCEP
As of 2023, the U.S. National Cholesterol Education Program Adult Treatment Panel III remains widely used. It requires at least three of the following:- Central obesity: waist circumference ≥102 cm men; ≥88 cm women
- Dyslipidaemia: TG ≥1.7 mmol/L
- Dyslipidaemia: HDL-C <40 mg/dL, <50 mg/dL
- Blood pressure ≥130/85 mmHg
- Fasting plasma glucose ≥6.1 mmol/L
2009 Interim Joint Statement
- Elevated waist circumference
- Triglycerides ≥150 mg/dL
- Reduced HDL-C men; ≤50 mg/dL
- Elevated blood pressure
- Fasting glucose ≥100 mg/dL
The prior IDF and revised NCEP definitions are similar, but differ on assumptions when body mass index ≥30 kg/m2 and on geography-specific waist cut points.
WHO
The World Health Organization requires one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance and two of:- Blood pressure ≥140/90 mmHg
- Dyslipidemia: TG ≥1.695 mmol/L and HDL-C ≤0.9 mmol/L, ≤1.0 mmol/L
- Central obesity: waist:hip ratio >0.90 ; >0.85, or BMI >30 kg/m2
- Microalbuminuria: urinary albumin excretion ≥20 μg/min or albumin:creatinine ≥30 mg/g
EGIR
- Central obesity: waist ≥94 cm men; ≥80 cm women
- Dyslipidaemia: TG ≥2.0 mmol/L and/or HDL-C <1.0 mmol/L or treated for dyslipidaemia
- Blood pressure ≥140/90 mmHg or antihypertensive medication
- Fasting plasma glucose ≥6.1 mmol/L
Cardiometabolic index
Other
is used to predict cardiovascular risk in metabolic syndrome and may predict nonalcoholic fatty liver disease. Reproductive disorders and erectile dysfunction or decreased total testosterone in men have also been associated.Prevention
Prevention of metabolic syndrome centres on improving modifiable lifestyle factors that contribute to excess visceral fat, insulin resistance, and cardiometabolic risk. Even modest, sustained changes in activity and diet have been shown to improve multiple components of the syndrome.Regular physical activity is strongly supported by clinical and public-health organizations. Guidelines from the American Heart Association recommend at least 150 minutes per week of moderate-intensity aerobic activity, or 75 minutes of vigorous activity, with additional muscle-strengthening exercises on two or more days per week. Walking—even in shorter bouts that accumulate to 30 minutes per day—is associated with measurable improvements in blood pressure, insulin sensitivity, and waist circumference.
Dietary patterns emphasizing whole foods appear beneficial. Evidence from observational studies and randomized trials supports Mediterranean-style eating, which is associated with reduced central adiposity and improved lipid and glycaemic measures. Calorie reduction, improved diet quality, and lowering intake of refined carbohydrates also contribute to improved metabolic parameters. Time-restricted eating has shown preliminary benefits in reducing waist circumference and fasting glucose in adults with metabolic syndrome, though long-term effects remain under investigation.
Other behavioural factors influence prevention outcomes. Adequate sleep duration and quality have been linked to lower cardiometabolic risk, with insufficient sleep associated with higher rates of hypertension, obesity, and dysregulated glucose metabolism. Reducing alcohol intake may also be protective, as heavy use can worsen hepatic and metabolic outcomes in people with underlying metabolic risk.
Although individual-level changes are effective for many people, adherence varies widely in real-world settings. Public-health bodies—including the International Obesity Taskforce—argue that sustained prevention requires population-level interventions, such as improved access to healthy foods, urban design that supports physical activity, and policies addressing socioeconomic drivers of obesity.