Metabolic syndrome

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 (especially in concurrent obesity) 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 > (men) and > (women) 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 (particularly sugar-sweetened beverages), 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 (TNF-α) 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 (e.g., adiponectin, resistin, PAI-1). 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. Overfeeding with sucrose/fructose, particularly with high-fat intake, can induce features of metabolic syndrome in animals. Arachidonic acid–derived mediators (eicosanoids; 2-arachidonoylglycerol; anandamide) may link lipid oversupply and inflammation. == Diagnosis ==

NCEP As of 2023, the U.S. National Cholesterol Education Program Adult Treatment Panel III (2001) remains widely used. • Central obesity: waist circumference ≥102 cm (40 in) men; ≥88 cm (35 in) women • Dyslipidaemia: TG ≥1.7 mmol/L (150 mg/dL) • Dyslipidaemia: HDL-C 0.90 (men); >0.85 (women), or BMI >30 kg/m2 • Microalbuminuria: urinary albumin excretion ≥20 μg/min or albumin:creatinine ≥30 mg/g EGIR 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: • 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 • Fasting plasma glucose ≥6.1 mmol/L (110 mg/dL) Cardiometabolic index 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. CMI has also been explored alongside cardiovascular disease and erectile dysfunction. Anti-inflammatory dietary patterns may improve related markers. Other High-sensitivity C-reactive protein is used to predict cardiovascular risk in metabolic syndrome and may predict nonalcoholic fatty liver disease. 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. == 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 (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. 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. == Management ==

Management focuses on reducing cardiovascular and metabolic risk through lifestyle modification, pharmacologic therapy, and, in selected cases, surgery. Members of the intervention group were ~33% more likely to experience remission of metabolic syndrome. Diet and meal timing A Mediterranean-style eating pattern emphasizing vegetables, fruits, whole grains, legumes, nuts, and unsaturated fats—is associated with improvements in blood pressure, lipids, insulin sensitivity, and cardiovascular risk. Physical activity and weight reduction Weight loss of ~7–10% over 6–12 months improves BP, lipids, and insulin sensitivity. Sleep, tobacco, and alcohol Inadequate/irregular sleep and untreated obstructive sleep apnoea increase metabolic and CV risk. Smoking increases insulin resistance and CV risk; cessation reduces adverse outcomes. High alcohol intake raises BP, TGs, and hepatic steatosis; moderation is advised. Surgery 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. Guidelines endorse surgery for BMI ≥35 kg/m², or ≥30 kg/m² with metabolic complications. == Epidemiology ==

Approximately 20–25% of the world's adults have metabolic syndrome. more recent estimates are ~34%. In young children, there is no consensus on measurement; age-specific cut points are not well established. Continuous risk scores are often used instead. Microbiome composition and some conditions have been associated with metabolic syndrome, sometimes with gender-specific patterns. == History ==

In 1921, Joslin reported the association of diabetes with hypertension and hyperuricaemia. In 1923, Kylin expanded on this triad. In 1947, Vague observed that upper-body obesity predisposed to diabetes, atherosclerosis, gout and calculi. The term metabolic syndrome began appearing in the late 1950s. In 1967, Avogaro, Crepaldi and coworkers described moderately obese people with diabetes, hypercholesterolemia, and marked hypertriglyceridemia that improved on hypocaloric, low-carbohydrate diets. In 1977, Hans Haller used the term for associations of obesity, diabetes mellitus, hyperlipoproteinemia, hyperuricemia, and hepatic steatosis. The same year, Singer used it for associations of obesity, gout, diabetes, and hypertension with hyperlipoproteinemia. 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. The first comprehensive definition of the metabolic syndrome was given in 1981 by the German researchers Markolf Hanefeld and Wolfgang Leonhardt, Dresden, who defined it as a cluster of obesity, hyper- and dyslipoproteinemia, type 2 diabetes, gout, and hypertension, associated with an increased incidence of atherosclerotic vascular disease, fatty liver disease, and gallstones. In 1988, Gerald M. Reaven's Banting lecture proposed insulin resistance as the underlying factor and coined syndrome X. == See also ==