A man with marked central obesity, a hallmark of metabolic syndrome. His weight is 182 kg (400 lbs), height 185 cm (6 ft 1 in), andbody mass index (BMI) 53 (normal 18.5 to 24.9).
Metabolic syndrome is associated with the risk of developingcardiovascular disease andtype 2 diabetes.[1] In the U.S., about 25% of the adult population has metabolic syndrome, a proportion increasing with age, particularly among racial and ethnic minorities.[2][3]
Insulin resistance, metabolic syndrome, andprediabetes are closely related to one another and have overlapping aspects. Thesyndrome is thought to be caused by an underlying disorder of energy utilization and storage, but the cause of the syndrome is an area of ongoingmedical research. Researchers debate whether a diagnosis of metabolic syndrome implies differential treatment or increases risk ofcardiovascular disease beyond what is suggested by the sum of its individual components.[4]
Neck circumference has been used as a simple surrogate index of upper-body subcutaneous fat. Values >40.25 cm (15.85 in) (men) and >35.75 cm (14.07 in) (women) are considered high risk for metabolic syndrome, and large neck circumference more than doubles risk.[7] In adults with overweight/obesity, clinically significant weight loss may protect against COVID-19,[8] and neck circumference has been associated with increased risk of mechanical ventilation and mortality in hospitalized COVID-19 patients.[9][10]
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. Importantrisk factors include diet (particularly sugar-sweetened beverages),[13] genetics,[14][15][16][17] aging, sedentary behaviour[18] or low physical activity,[19][20] disruptedchronobiology/sleep,[21] mood disorders and some medications,[22][23] and excessive alcohol use.[24] The pathogenic role of excessive adipose expansion under sustainedovereating and resultinglipotoxicity has also been proposed.[25]
Modern "Western diet" patterns with high intake of energy-dense processed foods are a factor in the development of metabolic syndrome.[29] Rather than total adiposity, the core clinical component is visceral/ectopic fat, and the principal metabolic abnormality is insulin resistance.[30] A chronic energy surplus unmatched by activity may lead to mitochondrial dysfunction and insulin resistance.[31]
It is common for there to be a development ofvisceral fat, after whichadipocytes increaseplasma levels ofTNF-α and alter levels of other adipokines (e.g.,adiponectin,resistin,PAI-1). TNF-α can induce inflammatorycytokines and may trigger insulin resistance.[36] 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.[37][38]
This statement recognises population differences in waist risk thresholds and encourages common criteria with agreed cut points for international comparisons.[45]
The prior IDF and revised NCEP definitions are similar, but differ on assumptions whenbody mass index ≥30 kg/m2 and on geography-specific waist cut points.[citation needed]
TheWorld Health Organization (1999)[46] requires one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistanceand two of:
The European Group for the Study of Insulin Resistance (1999) requires insulin resistance (top 25% fasting insulin among nondiabetic individuals)and two or more of:[47]
Central obesity: waist ≥94 cm (37 in) men; ≥80 cm (31.5 in) women
Dyslipidaemia: TG ≥2.0 mmol/L (177 mg/dL) and/or HDL-C <1.0 mmol/L (38.61 mg/dL) or treated for dyslipidaemia
Blood pressure ≥140/90 mmHg or antihypertensive medication
The Cardiometabolic Index (CMI) estimates risk of type 2 diabetes,non-alcoholic fatty liver disease, and metabolic issues from waist-to-height ratio and triglycerides-to-HDL-C ratio.[48] CMI has also been explored alongside cardiovascular disease and erectile dysfunction.[49] Anti-inflammatory dietary patterns may improve related markers.[50]
High-sensitivity C-reactive protein is used to predict cardiovascular risk in metabolic syndrome and may predictnonalcoholic fatty liver disease.[51] Reproductive disorders (such as polycystic ovary syndrome in women of reproductive age) and erectile dysfunction or decreased total testosterone in men have also been associated.[52]
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.[53][54]
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.[55] 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.[54]
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.[56] Calorie reduction, improved diet quality, and lowering intake of refined carbohydrates also contribute to improved metabolic parameters.[57] Time-restricted eating (a form of intermittent fasting) has shown preliminary benefits in reducing waist circumference and fasting glucose in adults with metabolic syndrome, though long-term effects remain under investigation.[58]
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.[59] Reducing alcohol intake may also be protective, as heavy use can worsen hepatic and metabolic outcomes in people with underlying metabolic risk.[60]
Although individual-level changes are effective for many people, adherence varies widely in real-world settings.[57] 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.[61]
Management focuses on reducing cardiovascular and metabolic risk through lifestyle modification, pharmacologic therapy, and, in selected cases, surgery.[54] Because metabolic syndrome represents a cluster of interrelated conditions, treatment typically targets each component individually rather than the syndrome as a single entity.[62]
A Mediterranean-style eating pattern—emphasising vegetables, fruits, whole grains, legumes, nuts, and unsaturated fats—is associated with improvements in blood pressure, lipids, insulin sensitivity, and cardiovascular risk.[56] Reduced-carbohydrate approaches may lower glucose and promote weight loss in insulin-resistant individuals.[57] Evidence on meal timing suggests time-restricted eating or avoidance of late-night meals can modestly improve glycaemic and lipid markers, though long-term data are limited.[58] Guidance recommends tailoring dietary advice to personal preference, culture, and access to improve adherence.[54]
Ongoing follow-up includes monitoring waist circumference, body weight, blood pressure, lipids, and fasting glucose or HbA1c.[54] Recent guidance emphasises equitable care through culturally appropriate counselling, affordable medication access, and community-based support.[63]
Treatment of individual risk factors follows established cardiovascular and diabetes guidelines.[62]
Blood pressure: First-line agents include thiazide-type diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers. Selection depends on comorbid conditions and tolerance.[62]
Dyslipidaemia: Statins remain first-line therapy for lowering low-density lipoprotein cholesterol (LDL-C). Fibrates or omega-3 fatty acids may be added for persistent severe hypertriglyceridaemia.[64]
Glucose control: Lifestyle intervention is the foundation of therapy. When medications are required, glucose-lowering agents with demonstrated cardiovascular and renal benefits—such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors—are preferred for individuals with type 2 diabetes or elevated cardiovascular risk.[53]
Obesity management: Pharmacotherapies such as semaglutide and tirzepatide produce clinically significant weight loss and improvements in blood pressure, lipids, and glycaemic control. Randomized controlled trials have reported reduced major adverse cardiovascular events in adults with overweight or obesity and established cardiovascular disease.[65][66]
Weight loss of ~7–10% over 6–12 months improves BP, lipids, and insulin sensitivity.[54] Public-health guidance advises ≥150 min/week moderate aerobic activity (or 75 min vigorous) plus muscle-strengthening ≥2 days/week.[55]
Metabolic (bariatric) surgery is considered when lifestyle and pharmacotherapy are insufficient. Surgery is associated with durable weight loss and partial or complete remission of type 2 diabetes, hypertension, and dyslipidaemia.[67] Guidelines endorse surgery for BMI ≥35 kg/m², or ≥30 kg/m² with metabolic complications.[68]
Approximately 20–25% of the world's adults have metabolic syndrome.[61] In 2000, ~32% of U.S. adults met criteria;[69][70] more recent estimates are ~34%.[70][71]
In young children, there is no consensus on measurement; age-specific cut points are not well established.[72] Continuous risk scores are often used instead.[73] Microbiome composition and some conditions have been associated with metabolic syndrome, sometimes with gender-specific patterns.[74][75]
In 1921, Joslin reported the association of diabetes with hypertension and hyperuricaemia.[76]In 1923, Kylin expanded on this triad.[77]In 1947, Vague observed that upper-body obesity predisposed todiabetes,atherosclerosis,gout andcalculi.[78]The termmetabolic syndrome began appearing in the late 1950s. In 1967, Avogaro, Crepaldi and coworkers described moderately obese people with diabetes,hypercholesterolemia, and markedhypertriglyceridemia that improved on hypocaloric, low-carbohydrate diets.[79]In 1977, Haller used the term for associations of obesity, diabetes mellitus,hyperlipoproteinemia,hyperuricemia, andhepatic steatosis.[80] The same year, Singer used it for associations of obesity, gout, diabetes, and hypertension with hyperlipoproteinemia.[81]In 1977–1978, Gerald B. Phillips proposed a "constellation of abnormalities" (glucose intolerance,hyperinsulinemia,hypercholesterolemia,hypertriglyceridemia, hypertension) and hypothesised sex hormones as a linking factor.[82][83]In 1988,Gerald M. Reaven'sBanting lecture proposed insulin resistance as the underlying factor and coinedsyndrome X.[84]
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