Metabolic syndrome (MS) refers to a pathological state characterized by metabolic disorders involving proteins, fats, and carbohydrates, representing a complex cluster of metabolic abnormalities. The central components of MS are obesity and insulin resistance. MS is a significant risk factor for cardiovascular and cerebrovascular diseases, with the incidence and mortality rates for cardiovascular events being 2 to 3 times higher in individuals with MS compared to the general population.
Etiology and Pathogenesis
MS arises from the interplay between genetic and environmental factors. The development and progression of its various components are closely interconnected and mutually influencing, likely sharing an underlying pathophysiological basis. Insulin resistance (IR) serves as the central mechanism of MS and is strongly associated with obesity, particularly central obesity. IR refers to reduced sensitivity of insulin target organs (such as the liver, muscle, and adipose tissue) to the action of insulin. In the early stages, the body compensates for IR by secreting excess insulin, resulting in hyperinsulinemia. There is a complex bidirectional relationship between IR, hyperinsulinemia, obesity, and the pathological changes of MS.
The mechanisms by which obesity induces IR are associated with disturbances in hormones and cytokines derived from adipocytes, including elevated levels of free fatty acids (FFA), tumor necrosis factor-alpha (TNF-α), leptin, resistin, and plasminogen activator inhibitor-1 (PAI-1), as well as reduced levels of adiponectin.
IR contributes to the development of MS-related diseases through various direct and indirect mechanisms:
Type 2 Diabetes Mellitus (T2DM)
In the state of IR, pancreatic β-cells initially compensate by increasing insulin secretion to maintain normal blood glucose levels. When β-cell function deteriorates and decompensation occurs, T2DM develops.
Hypertension
Hyperinsulinemia activates the sympathetic nervous system, increases cardiac output, causes vascular constriction and smooth muscle proliferation, and enhances renal sodium reabsorption.
Dyslipidemia
In the IR state, insulin's ability to suppress the release of FFAs is impaired. Increased synthesis of very low-density lipoprotein (VLDL) and reduced activity of lipoprotein lipase (LPL) lead to decreased breakdown of chylomicrons (CM) and VLDL. This results in elevated levels of triglyceride (TG)-enriched lipoproteins (CM and VLDL). The action of cholesterol ester transfer protein (CETP) and hepatic lipase (HL) further promotes the formation of small, dense LDL (sLDL). The increased levels of TG-rich lipoproteins also reduce HDL levels, particularly HDL-2. The key lipid abnormalities in MS include elevated TG, increased sLDL, and reduced HDL.
Endothelial Dysfunction
Elevated blood glucose, increased sLDL, and abnormalities in adipokine levels contribute to reduced nitric oxide (NO) release and impaired vascular relaxation in the IR state.
Coagulation and Fibrinolysis Abnormalities
IR is associated with higher levels of fibrinogen, von Willebrand factor (vWF), and PAI-1, alongside reduced antiplatelet aggregation, leading to a hypercoagulable state.
Chronic Low-grade Inflammation
Obesity-associated metabolic disturbances trigger an increase in pro-inflammatory cytokines, acute-phase reactants, and activation of inflammatory signaling pathways, resulting in a persistent low-grade inflammatory response.
Although IR is central to the pathogenesis of MS, it is not the sole mechanism. Not all individuals with MS exhibit IR, and not all individuals with IR develop MS. This suggests that the clustering of multiple metabolic risk factors for cardiovascular disease in individuals may have a more complex or multifaceted pathological basis.
Clinical Manifestations
The clinical manifestations of MS correspond to the symptoms and complications of its component diseases and associated conditions, which may appear simultaneously or sequentially. These include presentations from obesity, dyslipidemia, diabetes, hypertension, coronary heart disease, and stroke.
Diagnosis
The diagnostic criteria for metabolic syndrome (MS) require the presence of three or more of the following components:
- Abdominal Obesity (Central Obesity): Waist circumference ≥90 cm in men and ≥85 cm in women.
- Hyperglycemia: Fasting blood glucose ≥6.1 mmol/L (110 mg/dL) or blood glucose ≥7.8 mmol/L (140 mg/dL) two hours after glucose load, and/or a history of diagnosed diabetes currently under treatment.
- Hypertension: Blood pressure ≥130/85 mmHg, and/or a history of diagnosed hypertension currently under treatment.
- Elevated Triglycerides (TG): Fasting TG levels ≥1.7 mmol/L (150 mg/dL).
- Low High-Density Lipoprotein Cholesterol (HDL-C): Fasting HDL-C <1.04 mmol/L (40 mg/dL).
Prevention and Treatment
The primary goal of MS prevention and management is to reduce the risk of cardiovascular diseases, while for individuals who already have existing cardiovascular conditions, secondary prevention of cardiovascular events is emphasized. In principle, lifestyle interventions are prioritized first, and if these interventions fail to achieve the desired outcomes, pharmacological treatment to control individual risk factors may be required.
Lifestyle Interventions
Fundamental measures include adopting a balanced diet, engaging in appropriate physical activity, achieving weight reduction, and smoking cessation.
Pharmacological Treatment
Medications targeting specific components, such as diabetes, hypertension, dyslipidemia, and obesity, are administered to achieve optimal control.
Treatment Goals：
- Weight Management: A reduction of 7%–10% in body weight within one year, with the aim of normalizing BMI and waist circumference.
- Blood Pressure: Less than 130/80 mmHg for individuals with diabetes, and less than 140/90 mmHg for those without diabetes.
- Lipid Profile: LDL-C <2.6 mmol/L, TG <1.7 mmol/L, and HDL-C >1.04 mmol/L for men or >1.3 mmol/L for women.
- Glycemic Control: Fasting blood glucose <6.1 mmol/L, blood glucose <7.8 mmol/L two hours after glucose load, and HbA1c <7%.