Obesity and metabolic syndrome are two very common and interrelated conditions with immense public health implications. Most individuals with obesity have metabolic comorbidities, although metabolically healthy obesity is possible. Metabolic syndrome refers to a constellation of medical conditions that increase the risk of several health problems, primarily atherosclerotic cardiovascular disease, type 2 diabetes, and hepatic steatosis. These conditions are insulin resistance (considered the main risk factor), hypertension, dyslipidemia, and abdominal obesity. The initial treatment of metabolic syndrome typically focuses on initiating lifestyle changes that promote weight reduction, such as dietary modifications and physical exercise. Weight reduction often results in lowered blood pressure and triglyceride levels, as well as increased insulin sensitivity. Lifestyle modifications are recommended to all patients, but some may also benefit from pharmacological treatment or bariatric surgery. Comorbid conditions, such as persistent hypertension and insulin resistance, should be treated appropriately (e.g., ACE inhibitors, metformin).
Metabolic syndrome 
- Definition: a constellation of medical conditions that commonly manifest together and significantly increase the risk for cardiovascular disease and type 2 diabetes mellitus
Criteria for metabolic syndrome: ≥ 3 must be present (i.e., the patient is either diagnosed with or receiving treatment for the condition)
- Elevated blood glucose: fasting glucose ≥ 100 mg/dL
- Elevated blood pressure: systolic ≥ 130 mmHg and/or diastolic ≥ 85 mm Hg
- Elevated triglycerides: ≥ 150 mg/dL
- Men: < 40 mg/dL
- Women: < 50 mg/dL
- Abdominal obesity ; 
|Interpretation of Body Mass Index|
|Underweight||< 18.5 kg/m2|
|Healthy weight||18.5–24.9 kg/m2|
|Overweight||≥ 25–29.9 kg/m2 |
|Class 1 obesity||30–34.9 kg/m2|
|Class 2 obesity||35–39.9 kg/m2|
|Class 3 obesity||≥ 40 kg/m2|
- Obesity: an excessive accumulation of fat tissue that results in increased health risks
- Metabolically healthy obesity (MHO): obesity without metabolic syndrome 
- Normal-weight obesity: Individuals with a normal BMI may still have elevated body fat content and therefore be at increased risk for metabolic comorbidities. 
Prevalence of metabolic syndrome 
- Adolescents (12–19 years of age)
- In the US, the prevalence of metabolic syndrome is higher in individuals of lower socioeconomic status.
- Prevalence of obesity
Epidemiological data refers to the US, unless otherwise specified.
- Features of obesity and metabolic syndrome
- Associated conditions
Initial screening 
- All adult patients should be regularly screened for obesity by measuring height and weight and calculating BMI.
- An elevated BMI should prompt a more comprehensive evaluation to identify indications for early interventions. 
Comprehensive assessment of a patient with overweight or obesity 
Perform at baseline and repeat at least once a year to detect comorbidities and associated conditions. Assessment allows for early treatment and evaluation of the patient's response to therapeutic interventions.
Clinical evaluation 
- Obtain a thorough patient history.
- Calculate BMI; measure waist circumference and blood pressure.
Laboratory studies 
- Routine studies
- Further studies: may be obtained as part of a more detailed evaluation based on clinical suspicion 
- Liver chemistries: Elevated transaminases suggest nonalcoholic fatty liver disease.
- Uric acid: Hyperuricemia is common and is related to higher oxidative stress. 
- Coagulation studies: Fibrinogen, plasminogen activator inhibitor-1, and other coagulation factors may be elevated.
- CRP: potentially elevated
- Urine microalbumin: may detect microalbuminuria
Depending on clinical evaluation, screening for associated conditions may be indicated.
- Preventing morbidity and mortality by lowering the risk of cardiovascular disease (see also “ ”)
- Reduction of body weight 
- Modification of risk factors by lowering lipids, blood pressure, and glucose to physiologic values
- All patients: Encourage lifestyle interventions and address modifiable factors.
- Adjuvant therapies (e.g., lipase inhibitors, bariatric surgery): Individualize based on BMI and comorbidities. 
- BMI ≥ 27 kg/m2 PLUS obesity-related comorbidities: Consider weight loss drugs as an adjunctive treatment.
- BMI > 30 kg/m2
- BMI ≥ 35 kg/m2 PLUS obesity-related comorbidities OR BMI ≥ 40 kg/m2: Bariatric surgery is indicated.
is a valid option if sufficient weight loss cannot be achieved through lifestyle modifications with or without pharmacological intervention. 
General measures 
Lifestyle modifications: The following recommendations are indicated for all patients.
- Dietary changes
Physical activity 
- Most patients: at least 30 minutes of moderate aerobic activity 5–7 times per week (e.g., brisk walking)
- High-risk patients (e.g., history of cardiovascular disease, congestive heart failure): medically supervised exercise programs
- Additional measures (if applicable)
|Examples of drugs associated with weight gain and potential alternatives |
|Atypical antipsychotics|| |
Before starting pharmacological treatment, discuss the side effects and limitations of the drugs with the patient and emphasize the importance of maintaining dietary changes and physical activity. Ensure regular follow-up to assess side effects and success. 
|Weight loss drugs |
|Opioid antagonists/norepinephrine-dopamine reuptake inhibitors|| |
Start therapy with small doses and escalate gradually depending on tolerance. Follow up every 1–3 months to assess side effects and success of the treatment, and modify therapy as necessary. 
- Mechanism of action: Reversibly inhibits gastric and pancreatic lipase, resulting in a decrease in fat breakdown and absorption
- Indication: weight loss in obese patients
- Recommendation: should be taken with meals containing fat
- Adverse effects: gastrointestinal side effects
- Endocrinologic: type 2 diabetes 
We list the most important complications. The selection is not exhaustive.
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