US Pharm. 2024;49(11):10-12.

Metabolic syndrome refers to the presence of a cluster of risk factors specific for developing type 2 diabetes (T2D). Individuals with metabolic syndrome have a five times greater risk of developing diabetes than the general population. T2D is characterized by a deregulation of the carbohydrates, lipids, and proteins found in the metabolism and results in diminished secretion of insulin, resistance to insulin, or a combination of both.¹

The National Heart, Lung, and Blood Institute (NHLBI) identifies five key factors of metabolic syndrome, as follows:

Abdominal Obesity: This is defined as having a waist circumference greater than 40 inches for men and 35 inches for women. Abdominal obesity is the type of obesity most strongly associated with metabolic syndrome.

High Blood Pressure: Blood pressure of 130/80 mmHg or higher is considered elevated. Normal blood pressure is less than 120/80 mmHg. High blood pressure is common in individuals with insulin resistance and is strongly linked to obesity.

Impaired Fasting Blood Glucose: Fasting blood glucose level of 100 mg/dL or higher is considered impaired.

High Triglyceride Levels: Triglyceride levels exceeding 150 mg/dL are classified as high.

Low HDL Cholesterol: Low HDL is defined as less than 40 mg/dL for men and less than 50 mg/dL for women.

The NHLBI and the American Heart Association (AHA) recommend a diagnosis of metabolic syndrome when a patient has three or more of these factors. This column briefly discusses the causes, risk factors, symptoms, diagnosis, and treatment of this metabolic complication.²

CAUSES

The exact cause of metabolic syndrome is not yet fully understood, but several factors are interconnected. Obesity and a sedentary lifestyle contribute to the risk of developing metabolic syndrome. As noted, high cholesterol, impaired fasting blood glucose, and high blood pressure can increase the risk of cardiovascular disease and T2D.²

Because metabolic syndrome is closely linked to insulin resistance, many healthcare providers believe that insulin resistance may be a contributing factor to metabolic syndrome. In fact, metabolic syndrome is often referred to as insulin resistance syndrome. Some researchers suggest that hormonal changes resulting from chronic stress can lead to abdominal obesity, insulin resistance, and elevated blood lipids, such as triglycerides and cholesterol.³

Other factors, such as inflammatory cytokines, can increase insulin resistance in the liver, skeletal muscles, and adipose tissues. Adipose tissues release free fatty acids, which can further promote insulin resistance and inhibit insulin secretion from the pancreas. Sympathetic activation is a key feature of metabolic syndrome and is linked to several of its common components, including visceral obesity and high blood pressure.³

Additional factors that may contribute to metabolic syndrome include genetic variations affecting the body’s ability to process blood lipids, aging, imbalances in gut microbiota, and irregular distribution of body fat.³

RISK FACTORS

Obesity, which is often present in individuals with metabolic syndrome, makes it harder for the body’s cells to respond to insulin. Insulin is produced to help move glucose into cells for energy. When the body cannot produce enough insulin to overcome this resistance, blood sugar levels rise, leading to T2D.^4,5

As the U.S. population ages and the likelihood of developing metabolic syndrome increases with age, the AHA predicts that metabolic syndrome will soon become the leading risk factor for cardiovascular disease, surpassing cigarette smoking. Additionally, scientists believe that the rising rates of obesity are closely linked to the increasing prevalence of metabolic syndrome.^3,4

Key risk factors closely associated with metabolic syndrome include:

Age: The likelihood of developing metabolic syndrome increases with age.

Ethnicity: African Americans and Mexican Americans are at higher risk. African American women are about 60% more likely than African American men to have the syndrome.

BMI: A BMI >25 is a significant risk factor.

Personal or Family History of Diabetes: Women who have had gestational diabetes and individuals with a family history of T2D are at increased risk.

Lifestyle Factors: Smoking, heavy alcohol consumption, stress, a high-fat diet, and a sedentary lifestyle also contribute to the risk of metabolic syndrome.

SYMPTOMS

Metabolic syndrome typically does not cause noticeable symptoms, with the only visible sign being a prominent abdomen; however, high blood pressure, elevated triglycerides, and obesity may indicate the presence of metabolic syndrome.

Individuals with insulin resistance may also develop acanthosis nigricans, characterized by darkened skin in areas such as the back of the neck, armpits, and under the breasts. In some cases, the symptoms of metabolic syndrome may resemble those of other health conditions.⁶

DIAGNOSIS

Various well-known organizations have established criteria for diagnosing metabolic syndrome. These criteria typically include abdominal obesity, a BMI >25, high triglycerides, low HDL cholesterol, high blood pressure, and impaired glucose tolerance. The impaired glucose tolerance test evaluates the body’s ability to process sugar.⁷

Elevated blood sugar can increase the likelihood of blood clot formation. This occurs when higher levels of plasma plasminogen activator and fibrinogen, both involved in clotting, are present in the bloodstream.⁷

TREATMENT MANAGEMENT

Based on present and past medical history, physicians will figure out the best treatment for their patients with consideration of age, overall health, and present illness.^7,8

Because metabolic syndrome increases the risk of developing more serious chronic conditions, getting treatment is very important. Without treatment, a person may develop cardiovascular disease and T2D. Other conditions that may develop as a result of metabolic syndrome include polycystic ovary syndrome, fatty liver, cholesterol gallstones, asthma, and sleep disorders.⁸

LIFESTYLE MANAGEMENT

Treatment usually involves lifestyle changes. This means losing weight, working with a dietitian to change the diet, and getting more exercise. Losing weight increases HDL cholesterol and lowers LDL cholesterol and triglycerides and can also reduce the risk of T2D.^7,8

Losing even a modest amount of weight can lower blood pressure and increase sensitivity to insulin. It can also reduce the amount of fat around the middle. Diet, behavioral counseling, and exercise lower risk factors more than diet alone. Other lifestyle changes include quitting smoking and cutting back on alcohol consumption.^7,8

Diet

The DASH (Dietary Approaches to Stop Hypertension) eating plan is an acceptable eating pattern for patients who have diabetes. In addition to promoting blood pressure control, this eating pattern has been shown to improve insulin resistance, hyperlipidemia, and even overweight/obesity. This balanced approach promotes consumption of a variety of foods (whole grains, fat-free or low-fat dairy products, fruits, vegetables, poultry, fish, and nuts) and is appropriate for the entire family.^8,9

Physical Activity

Exercise helps people who are overweight or obese through maintaining and adding lean body mass, or muscle tissue, while losing fat. It also helps a person lose weight faster than just following a healthy diet because muscle tissue burns calories faster. Walking, swimming, and yoga are great exercises for just about anyone. The patient should start slowly by walking 30 minutes daily for a few days a week. One may gradually increase the duration to longer periods most days of the week. Exercise lowers blood pressure and can help prevent T2D. It also helps a person feel better emotionally, reduces appetite, improves sleep, improves flexibility, and lowers LDL cholesterol.

According to the AHA, treating insulin resistance is key to changing other diabetes risk factors. In general, the best way to treat insulin resistance is by losing weight and increasing physical activity (see SIDEBAR 1).^7-9

Medication

Patients who have metabolic syndrome or are at risk for it may need to take medication for treatment. This is especially true if diet and other lifestyle changes have not made a difference. Physicians may prescribe medication to help lower blood pressure, improve insulin metabolism, lower LDL cholesterol, raise HDL cholesterol, increase weight loss, or some combination of these. Common prescription medications include the following¹⁰:

Metformin is a commonly prescribed first-line treatment for hyperglycemia in patients with metabolic syndrome.

Other Insulin Sensitizers include thiazolidinediones, such as pioglitazone and rosiglitazone.

Statins such as atorvastatin and rosuvastatin can help lower cholesterol levels.

Antihypertensives such as thiazide, angiotensin-converting enzyme inhibitors, and calcium channel blockers can help lower blood pressure.

Ozempic can be prescribed for patients who have metabolic syndrome, insulin resistance, or prediabetes.

Weight-Loss Surgery

Weight-loss surgery (bariatric surgery) is an effective treatment for morbid obesity in patients who have not been able to lose weight through diet, exercise, or medication. It may also help patients who are less obese but have significant complications from their obesity.¹¹

Studies have shown that gastric bypass surgery helped lower blood pressure, cholesterol, and body weight 1 year after the procedure.

Weight-loss surgery can be done in several ways, but all are malabsorptive, restrictive, or a combination of the two. Malabsorptive procedures change the way the digestive system works. Restrictive procedures greatly reduce the size of the stomach, allowing it to hold less food while maintaining digestive functions.¹¹

CONCLUSION

Many studies show that metabolic syndrome, regardless of how it is defined, is a significant predictor of T2D in many different populations, including Native Americans, Hispanics, Mexicans, Turks, Iranians, Mauritians, Chinese, Europeans, and those of European descent.

Although considerable heterogeneity existed among these studies, it is concluded that the association of diabetes with any metabolic syndrome is greater than the association of cardiovascular events with metabolic syndrome. This is because some of its components (in particular, fasting glucose and waist circumference) are more strongly associated with diabetes risk.¹²

REFERENCES

1. Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care. 2005;28:1769-1778.
2. National Heart, Lung, and Blood Institute. What is metabolic syndrome? May 18, 2022. www.nhlbi.nih.gov/health/metabolic-syndrome. Accessed September 30, 2024.
3. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Executive summary. Cardiol Rev. 2005;13(6):322-327.
4. Lim HS, Lip GY, Beevers DG, et al. Factors predicting the development of metabolic syndrome and type II diabetes against a background of hypertension. Eur J Clin Invest. 2005;35:324-329.
5. Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome. Circulation. 2009;120:1640-1645.
6. Mayo Clinic. Acanthosis nigricans. www.mayoclinic.org/diseases-conditions/acanthosis-nigricans/symptoms-causes/syc-20368983. Accessed September 30, 2024.
7. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific statement. Circulation. 2005;112(17):2735-2752.
8. Kaur J. A comprehensive review on metabolic syndrome. Cardiol Res Pract. 2014;2014:943162.
9. National Heart, Lung, and Blood Institute. DASH eating plan. December 29, 2021. www.nhlbi.nih.gov/education/dash-eating-plan. Accessed September 30, 2024.
10. WebMD. How do you treat metabolic syndrome? March 19, 2023. www.webmd.com/heart/metabolic-syndrome/how-do-you-treat-metabolic-syndrome. Accessed September 30, 2024.
11. Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2008. Obes Surg. 2009;19(12):1605-1611.
12. Gami AS, Witt BJ, Howard DE, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol. 2007;49:403-414.

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