RECOGNIZING AND DIAGNOSING METABOLIC SYNDROME

The first step in making a diagnosis of metabolic syndrome requires the recognition of cues (signs and symptoms), followed by interpretation and validation of the interpretation with diagnostic studies.

Signs and Symptoms of Metabolic Syndrome

A patient who presents with the following signs and symptoms raises the concern for metabolic syndrome and leads to further exploration. These signs and symptoms may include:

• Obesity, particularly abdominal adiposity
• Symptoms of hyperglycemia, including polyuria, polyphagia, blurry vision, restlessness, fatigue especially after eating a meal, and poor wound healing
• Retinopathy, which can result in visual impairment
• Peripheral neuropathy, including numbness, impairment of balance, weakness, tremors, cramps, and gait abnormalities
• Chest pain (angina)
• Shortness of breath
• Acanthosis nigricans, a brown to black hyperpigmentation of the skin with poorly defined margins and a velvety texture usually found in skin folds (axilla, navel, groin, neck)
• Xanthomas and xanthelasmas, yellow lipid deposits under the skin of the elbows, joints, tendons, knees, hands, feet, buttocks, and eyelids (xanthelasmas)
• Female hirsutism (male-patterned hair growth)
  (Wang, 2020; Ikomi, 2022; Davidson & Pradeep, 2023; Dahl, 2021; Culala,2021)

Diagnosing Metabolic Syndrome

Assessment for a diagnosis of metabolic syndrome begins with a medical and social history, review of systems, and physical examination.

HISTORY AND REVIEW OF SYMPTOMS

A medical history offers important information that can help to confirm the diagnosis and determine the extent of the problem. A person who has metabolic syndrome may already have been diagnosed with some components of the syndrome, such as obesity, hypertension, or dyslipidemia. A major complication of the syndrome (e.g., atherosclerotic artery disease, ischemic heart disease, diabetes) may also be present.

Because metabolic syndrome involves a patient’s diet and lifestyle, a history should include dietary habits as well as exercise and level of activity. A history of polycystic ovary syndrome (PCOS), immune system diseases such as psoriasis or treatment for cancer (both of which affect regulation of systemic metabolic homeostasis), history of gestational diabetes, sleep problems such as apnea, as well as medications used to treat allergies, bipolar disorder, depression, HIV, and schizophrenia should be obtained, all of which elevate risk for metabolic syndrome.

Family history is important because genetics can play a major role in the development of the syndrome. A family history that includes obesity, type 2 diabetes, and/or insulin resistance greatly increases the chance that the patient will develop metabolic syndrome.

Social history can be significant, providing clues to other risk factors, such as smoking, which reduces insulin sensitivity and contributes to abdominal obesity in both sexes. Heavy alcohol consumption (five or more drinks on any day or 15 or more per week for men, and four or more on any day or eight or more drinks per week for women) correlates with low serum HDL cholesterol levels, raised serum triglycerides, higher waist circumferences, and hyperinsulinemia. In contrast, mild-to-moderate consumption (no more than one to two drinks per day for men and no more than one drink per day for women) lowers the level of insulin and serum lipids. Obstructive sleep apnea decreases the level of HDL besides increasing the level of glucose, body weight, insulin resistance, and cardiovascular risk.

A thorough review of systems can be helpful for identifying related problems such as menstrual irregularities seen in polycystic ovarian syndrome (Swarup et al., 2022; Mohamed et al., 2023).

A list of current medications can help assess causes for overweight or obesity. Medications known to increase body weight can include:

• Psychiatric medications
• Antipsychotics (e.g., risperidone, haloperidol)
• Lithium
• Antidepressants
• SSRIs (e.g., citalopram)
• SNRIs (e.g., venlafaxine)
• Tricyclics (e.g., imipramine)
• Antiepileptic medications (e.g., valproate, carbamazepine, gabapentin)
• Antidiabetic medications (e.g., rosiglitazone, insulin)
• Steroids (e.g., prednisone, hormonal contraceptives, inhaled corticosteroids)
• Antihistamines (e.g., diphenhydramine, cetirizine)
  (Singh et al., 2021; Kumar, 2022; Watson, 2022)

Assessing Children and Adolescents

Since 1980, the prevalence of obesity among children and adolescents has almost tripled. Thirty-two percent of children in the United States are now overweight or obese (Johns Hopkins Medicine, 2023).

While assessment of metabolic syndrome in adults relies on criteria established by national or international agencies, assessment among children and adolescents has not been as clear. Most assessments have relied on adaptations based on adult criteria.

Child and adolescent assessment includes:

• General medical history
• Prenatal and birth history:
• Maternal obesity
• Maternal gestational diabetes
• Maternal smoking
• Gestational age
• Birth weight
• Neonatal concerns
• Developmental history, including:
• Any delays in motor, speech, or cognitive developmental and therapy received
• Infant feeding, including breastfeeding and duration
• Timing of introduction of complementary foods
• Current medications, such as:
• Glucocorticoids
• Antiepileptics
• Antipsychotics
• Growth history:
• Height and weight growth trajectories
• Onset of obesity and timing of weight concerns of child, adolescent, and family
• Previous obesity management, whether supervised or self-initiated
• Previous and current dieting and exercise behaviors
• Use of supplements
• Sleep routines, presence of snoring, or possible sleep apnea
• Exercise tolerance
• Specific signs and symptoms, including:
• Acne
• Hirsutism (girls)
• Morning headache and visual disturbance
• Nocturnal enuresis
• Constipation
• Hip and knee joint pain
• Gastrointestinal complaints
• Menstrual history
• Social history, including:
• Use of tobacco, alcohol, or recreational drugs
• Family income and food insecurity
• Behavioral risk factors:
• Nutrition and eating behaviors
• Physical activity
• Sedentary behaviors
• Time spent sitting
• Screen time per day
• Patterns of screen viewing
• Use of social media
(Jebeile et al., 2022)

PHYSICAL EXAM

The physical examination provides crucial information, including elevated blood pressure and abdominal obesity, which are two of the five diagnostic criteria for metabolic syndrome.

The patient is also assessed for physical manifestations of insulin resistance and dyslipidemia (peripheral neuropathy, retinopathy, acanthosis nigricans, hirsutism, xanthomas, xanthelasmas). The clinician listens for arterial bruits, which may indicate atherosclerotic disease (Swarup et al., 2022).

Measuring for Obesity

The most commonly used measure of obesity is body mass index (BMI), which is measured using the formula:

BMI = weight in kilograms ÷ height in meters squared
or
BMI = weight in pounds x 703 ÷ height in inches squared

BODY MASS INDEX CLASSIFICATIONS

Classification		BMI (kg/m2)
(CDC, 2022a)
Normal		18.5–24.9
Overweight		25.0–29.9
Obese	Class 1	30.0–34.9
	Class 2	35.0–39.9
	Class 3 (extreme obesity)	>40.0

BMI is interpreted differently for children and teens even though it is calculated with the same formula. Due to changes in weight and height with age, as well as their relation to body fatness, BMI levels among children and adolescents are expressed relative to other children of the same sex and age (CDC, 2022b).

Body mass index, though common, is a controversial method, as it cannot differentiate fat mass from lean mass or subcutaneous from visceral fat. Also, abdominal adiposity is harmful even when BMI is low. Because it matters where excess weight is carried, waist-to-hip ratio (WHR) is recommended as a more accurate measurement than BMI for determining the risk for developing serious health conditions. WHR has a stronger causal effect on risk of mortality regardless of the levels of adiposity and body composition (Kahn et al., 2022b).

METABOLIC SYNDROME AND WAIST-TO-HIP RATIO

Risk level	WHR (men)	WHR (women)
(Koperska, 2023)
Low	≤0.95	≤0.80
Moderate	0.96–1.0	0.81–0.85
High	>1.0	≥0.86

Measuring Blood Pressure

The second component of metabolic syndrome that can be picked up in a physical exam is high blood pressure. To be used as a diagnostic condition for metabolic syndrome, an adult’s blood pressure must be >130/85 mmHg (AHA, 2023). If a person is already taking antihypertensive medication, it is assumed that their blood pressure would normally be >130/85 mmHg.

BLOOD PRESSURE RANGES (mmHg)

Level	Systolic	And/or	Diastolic
(AHA, 2023)
Normal	<120	and	<80
Elevated	120–129	and	<80
Hypertension, stage 1	130–139	or	80–89
Hypertension, stage 2	>140	or	>90
Hypertensive crisis	>180	and/or	>120

A child or adolescent is diagnosed with hypertension when their average blood pressure is at or above the 95th percentile for their age, sex, and height when measured multiple times over three visits or more (Johns Hopkins Medicine, 2023).

DIAGNOSTIC STUDIES

The most common diagnostic studies for metabolic syndrome are for dyslipidemias, as shown in the table below.

BLOOD LIPID TESTING

Test	Concentrations (in mg/dL)
Fasting blood glucose	Normal: 70–100
Fasting triglycerides	Normal: <150 Borderline high: 150–199 High: 200–299 Very high: >500
Fasting total cholesterol	Normal: <200 Borderline high: 200–239 High: ≥240
Fasting HDL cholesterol	Poor: <40 for men, <50 for women Better: 40–50 for men, 50–59 for women Best: ≥60
LDL cholesterol	Normal: <70 Optimal: <100 Near optimal: 100–129 Borderline high: 130–159 High: 160–189 Very high: ≥190

Metabolic syndrome is characterized by fasting blood triglycerides >150 mg/dL and fasting blood HDL cholesterol <40 mg/dL in men and <50 mg/dL in women (Meigs, 2023).

Additional studies to consider include:

• Hemoglobin A1C (HbA1c)
• Thyroid studies
• Oral glucose tolerance test (AGTT)
• Serum BUN and creatinine
• Uric acid
• Liver studies (alanine transaminase [ALT], aspartate transaminase [AST])

Although not routinely done for the diagnosis of metabolic syndrome, imaging studies may be appropriate for patients with signs and symptoms of complications of the syndrome, such as chest pain, dyspnea, claudication, or obstructive sleep apnea. These may include:

• Rest/stress ECG
• Vascular or rest/stress echocardiography
• Stress single-photon emission computed tomography (SPECT)
• Cardiac positron emission tomography (PET)
• Nocturnal polysomnography testing for sleep-related breathing disorder
  (Wang, 2020; Johns Hopkins Medicine, 2023)

DIFFERENTIAL DIAGNOSES

Additional diagnoses are considered for each of the criteria used to identify patients with metabolic syndrome. For example, in patients with hypertension, investigation for secondary causes—such as obstructive sleep apnea or other sleep-related breathing disorders, renovascular disease, or disorders of renin and aldosterone metabolism—may be warranted under appropriate circumstances.

Alternative causes of hyperglycemia may include not only diabetes mellitus but also thyroid dysfunction, Cushing’s syndrome, and rarer endocrinopathies, such as glucagonomas and pheochromocytomas (Wang, 2020).