CAUSES/RISK FACTORS FOR METABOLIC SYNDROME

Metabolic syndrome appears to result from the interaction of a number of disorders that can be initiated separately. The development of metabolic syndrome is related to three issues:

• Weight. It is estimated that approximately 22% of people who are overweight and 60% of people who are obese have metabolic syndrome. The risk is believed to be directly related to the amount of abdominal fat, which is defined by waist circumference. However, not everyone who is overweight or obese has metabolic syndrome, and people who are of normal weight can also develop metabolic syndrome.
• Lack of exercise. Lack of exercise has been shown to be linked to a variety of diseases, including heart disease, cancer, and diabetes. Additionally, lack of exercise contributes to weight gain, being overweight, and becoming obese.
• Genetics. Research indicates that there may be a genetic link for the development of metabolic syndrome among family members.
  (Merck Manual, 2020; Sherif, 2017)

Although the specific chain of events leading to the appearance of metabolic syndrome is still not clear, much is known about the development and interactions of its separate components. Here is a summary of the causes of the individual components of metabolic syndrome.

Intra-Abdominal Obesity

Abdominal obesity is a significant predictor of metabolic syndrome. This is because abdominal (visceral) fat tends to be more resistant to insulin than fat in other areas of the body (Merck Manual, 2020). The amount of visceral fat, which tends to accumulate more in women after menopause, is the most important risk factor for metabolic syndrome (Sherif, 2017).

Having a large waistline means that there is excess body weight around the waist. A waist measurement of 35 inches or more for women or 40 inches or more for men is indicative of risk for metabolic syndrome. A large waistline is also a risk factor for other health problems such as cardiovascular disease (NHLBI, 2019).

GENETIC FACTORS THAT CONTRIBUTE TO OBESITY

In the past few decades, obesity has reached epidemic proportions in the United States. Genetics can play a significant role in the development of obesity. Studies of comparisons among family members, twins, and adoptees provide evidence that a sizable part of the variations in weight among adults is linked to genetic factors. Additionally, studies have identified variants in several genes that may contribute to the development of obesity by increasing hunger signals and food intake. Rarely, inherited obesity is caused by a specific variant of a single gene. The research that focuses on the genetic factors that contribute to the development of metabolic syndrome is at an early stage (CDC, 2018).

NONGENETIC FACTORS THAT CONTRIBUTE TO OBESITY

Prenatal. There are a number of factors that increase the risk for obesity beginning during the period of fetal development. These include a history of:

• Maternal smoking during pregnancy
• Gestational weight gain
• Gestational diabetes
  (Harvard School of Public Health, 2017)

Stress and anxiety can lead to overeating in an attempt to control negative emotions and find comfort. Sometimes referred to as stress eating, this type of eating can lead to significant weight gain.

Pharmacologic. Many medications have weight gain as a side effect, and it is important to monitor persons taking these medications. They include:

• Psychiatric drugs (e.g., lithium, atypical antipsychotics such as clozapine and olanzapine, and antidepressants such as the tricyclics)
• Neurologic drugs (e.g., antiepileptic drugs such as valproate)
• Steroids (e.g., hormonal contraceptives, prednisone)
• Antidiabetic drugs (e.g., insulin)
• Antihistamines
• Beta-blockers
  (Comerford, 2017)

Insulin Resistance

Insulin triggers the mechanisms that cells use to take up glucose from their surroundings. In addition, insulin tells cells to:

• Use their internal glucose for generating energy
• Store any excess internal glucose in the form of glycogen
• Stop releasing internal stores of glucose into the circulation

Under normal conditions, insulin molecules bind to the receptors on the cells of the body. When cell portals are activated by insulin, they open to allow glucose to enter the cell, where it is converted to energy. Insulin resistance exists when a given amount of insulin produces a less-than-expected biologic effect. In insulin resistance there is an increased insulin secretion to maintain normal glucose and lipid homeostasis.

Insulin resistance plays a major pathogenic role in the development of metabolic syndrome. Metabolic syndrome may include any or all of the following:

• Hyperinsulinemia
• Type 2 diabetes or glucose intolerance
• Central obesity
• Hypertension
• Dyslipidemia that includes high triglyceride levels
• Low HDL cholesterol level and small, dense low-density lipoprotein (LDL) particles
• Hypercoagulability
  (NHLBI, 2019)

GENETICS AND INSULIN RESISTANCE

As with many pathologic processes, insulin resistance develops most readily in people with a genetic predisposition for it. In predisposed people, it is possible that certain genes produce poorly functioning insulin receptor subunits or other molecules in the intracellular chain leading from the receptor to the actual glucose utilization machinery. It is still not clear, however, if any of these potential problems are common causes of the genetic predisposition to develop insulin resistance.

A family history of diabetes, lipid disorders, hypertension, or heart disease increases the risk for development of metabolic syndrome (NHLBI, 2019).

EXCESS VISCERAL FAT AND INSULIN RESISTANCE

Abdominal (visceral) obesity is a powerful predictor of metabolic syndrome because visceral fat tends to be more resistant to insulin than fat in other areas of the body. This resistance increases the release of free fatty acids into the portal system, which leads to increased apolipoprotein B, increased LDL, decreased HDL, and increased triglyceride levels. Because of elevated “bad” cholesterol and decreased “good” cholesterol, the risk of cardiovascular diseases also increases (Durkin, 2019).

Insulin resistance can be triggered by anything that causes high blood levels of free fatty acids, glucose, or insulin. Conditions that lead to insulin resistance through this mechanism include high levels of glucocorticoids (e.g., Cushing disease or long-term treatment with prednisone), nonalcoholic fatty liver disease, and treatment with protease inhibitors (e.g., for HIV).

Dyslipidemias

Dyslipidemia is an unhealthy amount of lipids circulating in the bloodstream. The specific dyslipidemias of metabolic syndrome include an increase in blood triglycerides and a decrease in blood HDL lipoproteins.

There are five types of lipoproteins:

• Chylomicrons: These are the largest and least dense of the lipoproteins and have the highest triglyceride content.
• VLDL (very-low-density lipoprotein): VLDL is composed of protein, fats, and cholesterol.
• IDL (intermediate-density lipoprotein): IDL is created by the metabolism of VLDL.
• LDL (low-density lipoprotein): This is the last remnant of VLDL and contains mostly cholesterol.
• HDL (high-density lipoprotein): HDL has the highest protein-to-lipid ratio and is the densest lipoprotein. It is referred to as good cholesterol because it transports cholesterol away from the tissues to the liver, which lowers blood cholesterol levels.
  (Ahmed et al., 2020)

GENETICS AND DYSLIPIDEMIAS

A number of different genetic mutations that affect fat cells will cause the dyslipidemias of metabolic syndrome. In addition, certain genetic mutations of apolipoproteins (e.g., familial combined hyperlipidemia) will cause high blood levels of triglycerides and low blood levels of HDL cholesterol.

Beyond direct genetic causes, the dyslipidemias of metabolic syndrome can result from a variety of problems.

METABOLIC DISORDERS AND DYSLIPIDEMIAS

The most common causes of dyslipidemias are other metabolic problems. Examples of such problems include:

• Diabetes
• Hypothyroidism
• Polycystic ovary syndrome
  (MedlinePlus, 2020a)

LIFESTYLE AND DYSLIPIDEMIAS

The same habits that tend to make a person obese will also cause lipid problems. Dyslipidemias can result from insufficient physical activity and a high-calorie diet with excess carbohydrates and excess saturated fats.

KIDNEY PROBLEMS AND DYSLIPIDEMIAS

Patients with chronic renal failure develop increased levels of triglycerides and decreased levels of HDL cholesterol. Later, if they receive kidney transplants, patients are put on immunosuppressive drugs, typically glucocorticoids and cyclosporine; these drugs also raise blood triglycerides and reduce blood HDL cholesterol (Comerford, 2017).

Hypertension

Hypertension develops when there is an increase in cardiac output, peripheral resistance, or both. There are a number of factors that play a role in the development of hypertension. These include:

• Family history
• Race (most common in African Americans)
• Stress
• Obesity
• Diet high in saturated fats or sodium
• Tobacco use
• Hormonal contraceptives
• Sedentary lifestyle
• Aging
  (Durkin, 2019)

GENETICS, RACE, AGE, AND HYPERTENSION

Hypertension has a tendency to run in families, especially in individuals with a family history from both parents. However, the genetic reasons for these patterns are not fully understood. In addition, the prevalence of the condition increases in people age 60 and over. African Americans are at highest risk to have hypertension starting at a younger age; often it is more severe and difficult to manage (Medline Plus, 2020b).

LIFESTYLE AND HYPERTENSION

Hypertension is a chronic condition that may be the result of lifestyle factors mentioned above, and it requires long-term management. Education and supportive resources to empower patients to make changes are the key to success for good control of blood pressure and prevention of complications. Changes including weight loss and management, increasing physical activity, encouraging the use of stress management strategies, reducing/limiting alcohol intake, and smoking cessation should be provided for patients with hypertension who are also at high risk for metabolic syndrome (Iqbal & Jamal, 2020).