Obesity and metabolic syndrome

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 ^[1]

• 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
  • Low HDL-C
    • Men: < 40 mg/dL
    • Women: < 50 mg/dL
  • Abdominal obesity ; ^[2]
    • Men: waist circumference ≥ 102 cm or > 40 in
    • Women: waist circumference ≥ 88 cm or > 35 in

Abdominal obesity (i.e., accumulation of fat in visceral tissue) is strongly associated with an atherogenic and hyperglycemic state.

Obesity ^[3]

The relation between an individual's height and weight is commonly assessed using the Body Mass Index (BMI).

• Obesity: an excessive accumulation of fat tissue that results in increased health risks
• Metabolically healthy obesity (MHO): obesity without metabolic syndrome ^[5][6]
• Normal-weight obesity: Individuals with a normal BMI may still have elevated body fat content and therefore be at increased risk for metabolic comorbidities. ^[3]

• Prevalence of metabolic syndrome ^[7]
  • Adults
    • ♀ ≈ ♂
    • ∼ 35%, increasing with age (∼ 55% among individuals ≥ 60 years of age)
    • Increasing over time (i.e., prevalence is higher now than it was in the past)
  • Adolescents (12–19 years of age)
    • ♂ > ♀
    • ∼ 6–11.5% depending on geographic region
  • In the US, the prevalence of metabolic syndrome is higher in individuals of lower socioeconomic status.
• Prevalence of obesity
  • ♀ > ♂
  • Adults: ∼ 40%
  • Adolescents (12–19 years of age): ∼ 20%

The worldwide prevalence of metabolic syndrome is estimated to be 20–25%. ^[8][9]

Obese children and adolescents are at a high risk of obesity in adulthood and developing the associated complications.

Epidemiological data refers to the US, unless otherwise specified.

• Features of obesity and metabolic syndrome
  • Increased body weight for height
  • Large abdominal circumference
  • High blood pressure
  • Fatigue and poor exercise tolerance
  • Musculoskeletal pain
  • Dermatologic manifestations: e.g., pseudoacanthosis nigricans , acrochordons , intertrigo ^[10]
• Associated conditions
  • GI conditions: cholelithiasis, nonalcoholic fatty liver disease, GERD, colonic diverticulosis ^[11]
  • Polycystic ovary syndrome ^[12]
  • Mental health issues: e.g., depression , anxiety, eating disorders ^[13]
  • Gout ^[3]

Initial screening ^[14]

• 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. ^[14]

Comprehensive assessment of a patient with overweight or obesity ^[15][16]

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.

All patients who are overweight or obese should be screened for metabolic syndrome.

Clinical evaluation ^[16]

• Obtain a thorough patient history.
  • Ask about factors contributing to overweight and obesity.
  • Ask about current medications.
  • Identify possible secondary causes of obesity.
• Calculate BMI; measure waist circumference and blood pressure.

Laboratory studies ^[2][17]

• Routine studies
  • Fasting lipid panel: Findings may be consistent with atherogenic dyslipidemia (e.g., ↑ triglycerides, ↑ LDL, ↓ HDL). ^[2]
  • Fasting glucose: Elevated fasting glucose suggests insulin resistance.
• Further studies: may be obtained as part of a more detailed evaluation based on clinical suspicion ^[2]
  • Liver chemistries: Elevated transaminases suggest nonalcoholic fatty liver disease.
  • Uric acid: Hyperuricemia is common and is related to higher oxidative stress. ^[17][18]
  • Coagulation studies: Fibrinogen, plasminogen activator inhibitor-1, and other coagulation factors may be elevated.
  • CRP: potentially elevated
  • Urine microalbumin: may detect microalbuminuria

Additional screening

Depending on clinical evaluation, screening for associated conditions may be indicated.

• Cardiovascular disease: Perform ASCVD risk assessment.
• Major depressive disorder: Ask about depressive symptoms.
• Obstructive sleep apnea: Screen for clinical features of obstructive sleep apnea.
• Osteoarthritis: Screen for osteoarthritis symptoms and examine joints.
• Malignancy: Ensure appropriate and timely cancer screening based on age and individual risk.

Approach ^[2][15][16]

• Treatment goals
  • Preventing morbidity and mortality by lowering the risk of cardiovascular disease (see also “ASCVD prevention”)
  • Reduction of body weight ^[2]
  • Modification of risk factors by lowering lipids, blood pressure, and glucose to physiologic values
    • Dyslipidemia: Statins are first-line. ^[2]
    • Hypertension: target BP < 140/90 mm Hg ^[2]
    • Diabetes mellitus: target HbA1c to near normal values (< 7%) ^[2]
• Interventions
  • All patients: Encourage lifestyle interventions and address modifiable factors.
  • Adjuvant therapies (e.g., lipase inhibitors, bariatric surgery): Individualize based on BMI and comorbidities. ^[15][16]
    • BMI ≥ 27 kg/m² PLUS obesity-related comorbidities: Consider weight loss drugs as an adjunctive treatment.
    • BMI > 30 kg/m²
      • With no additional comorbidities: Consider weight loss drugs as an adjunctive treatment.
      • Patients with severe comorbidities (e.g., diabetes, metabolic syndrome): Consider bariatric surgery. ^[4][19]
    • BMI ≥ 35 kg/m² PLUS obesity-related comorbidities OR BMI ≥ 40 kg/m²: Bariatric surgery is indicated.

Lifestyle modifications, the primary treatment for metabolic syndrome and obesity, can lead to weight reduction, increased insulin sensitivity, and reduction of cardiovascular risk factors. ^[15]

Bariatric surgery is a valid option if sufficient weight loss cannot be achieved through lifestyle modifications with or without pharmacological intervention. ^[20]

General measures ^[2][15]

• Lifestyle modifications: The following recommendations are indicated for all patients.
  • Dietary changes
    • Calorie restriction: 1200–1500 kcal per day in women; 1500–1800 kcal per day in men
    • Diet low in carbohydrates, sodium, cholesterol, saturated fats, and trans fats ^[2]
    • Consumption of fruit, vegetables, low-fat dairy, fish, and whole grains
  • Physical activity ^[2]
    • 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)
  • Smoking cessation and alcohol moderation
  • Avoid drugs that may contribute to weight gain.

Pharmacological management of obesity ^[15][16]

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. ^[16]

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. ^[16]

Orlistat

• 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
  • Abdominal pain
  • Diarrhea, steatorrhea
  • Increased bowel urgency and movements
  • Flatulence
  • Malabsorption of fat-soluble vitamins

• Endocrinologic: type 2 diabetes ^[2][15]
• Cardiovascular
  • Cardiovascular disease (ASCVD) ^[2][15]
  • Cardiomyopathy and congestive heart failure ^[21][22]
  • Thromboembolic complications, including portal vein thrombosis ^[23][24]
• Respiratory
  • Obstructive sleep apnea (OSA) ^[15]
  • Obesity hypoventilation syndrome (Pickwickian syndrome) ^[4]
  • Asthma ^[4]
• Reproductive
  • Adverse events during pregnancy (e.g., gestational hypertension and preterm labor) ^[25]
  • Hypofertility ^[4]
  • Erectile dysfunction ^[26]
• Others
  • Nonalcoholic steatohepatitis: increased risk of liver cirrhosis and hepatocellular carcinoma ^[3]
  • Chronic renal insufficiency ^[21]
  • Dementia ^[27]
  • Osteoarthritis, chronic back pain ^[15][19]
  • Malignancy: several cancers, including liver, colorectal, and breast cancer ^[28][29]

We list the most important complications. The selection is not exhaustive.

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