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Obesity and metabolic syndrome Last updated: April 11, 2023

Summary

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).

Definition

[1]
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

Low HDL-C

Men: < 40 mg/dL

Women: < 50 mg/dL

[2]
Abdominal obesity ;

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).

Interpretation of Body Mass Index

Underweight < 18.5 kg/m2

Healthy weight 18.5–24.9 kg/m2

Overweight ≥ 25–29.9 kg/m2 [4]

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
[5][6]
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. [3]

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Epidemiology

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.

Clinical features

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]

Diagnostics

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.

[17][18]
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

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.

Treatment

Approach [2][15][16]

Treatment goals

Preventing morbidity and mortality by lowering the risk of cardiovascular disease (see also “ASCVD
prevention”)
[2]
Reduction of body weight

Modification of risk factors by lowering lipids, blood pressure, and glucose to physiologic values

Dyslipidemia: Statins are first-line. [2]

[2]
Hypertension: target BP < 140/90 mm Hg

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

[4][19]
bariatric surgery.

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.

Examples of drugs associated with weight gain and potential alternatives [16]

Class Substance Alternative

Antidiabetics Insulin Metformin

Sulfonylureas GLP-1 agonists

Meglitinides SGLT-2 inhibitors

Antihypertensives Beta blockers ACE inhibitors

Angiotensin receptor blockers

Calcium channel blockers

Antidepressants SSRI: paroxetine SSRIs: fluoxetine, sertraline, citalopram,

escitalopram
TCAs: amitriptyline,
nortriptyline TCA: imipramine

SNRIs: venlafaxine, duloxetine Bupropion

Mirtazapine

Atypical Clozapine Potentially ziprasidone

antipsychotics Olanzapine

Quetiapine
Risperidone

Antiepileptics Gabapentin Weight neutral Aid in weight loss

Lamotrigine Felbamate
Pregabalin
Levetiracetam Topiramate
Valproic acid
Phenytoin Zonisamide
Vigabatrin

Carbamazepine

Contraceptives Injectable contraceptives Oral contraceptives

Antirheumatics Corticosteroids NSAIDs and DMARDs

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
[16]
regular follow-up to assess side effects and success.

Weight loss drugs [15][16]

Class Considerations Agents [16]

Lipase inhibitors Safe for most patients Orlistat

Useful for patients with diabetes and
dyslipidemia

Sympathomimetics Contraindicated in patients with: Phentermine/

Cardiovascular disease topiramate

Uncontrolled hypertension Diethylpropion

Opioid antagonists/norepinephrine-dopamine Carries a warning for Naltrexone/

suicidal thoughts and behaviors bupropion
reuptake inhibitors

GLP-1 agonists Beneficial in patients with Liraglutide

type 2 diabetes

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

Complications

Endocrinologic: type 2 diabetes [2][15]

Cardiovascular

Cardiovascular disease (ASCVD) [2][15]

[21][22]
Cardiomyopathy and congestive heart failure
[23][24]
Thromboembolic complications, including portal vein thrombosis

Respiratory

Obstructive sleep apnea (OSA) [15]

Obesity hypoventilation syndrome (Pickwickian syndrome) [4]

[4]
Asthma

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]
[21]
Chronic renal insufficiency
[27]
Dementia

Osteoarthritis, chronic back pain [15][19]

[28][29]
Malignancy: several cancers, including liver, colorectal, and breast cancer

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

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References

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