By: Sheela Lohiya, MD
Grandview Medical Group
Clinical Endocrinologist Board certified in Endocrinology, Diabetes and Metabolism
The metabolic syndrome (syndrome X, insulin resistance syndrome) consists of a constellation of metabolic abnormalities that confer increased risk of cardiovascular disease (CVD) and diabetes mellitus (DM). The major features of the metabolic syndrome include central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hyperglycemia, and hypertension.
Being overweight/obese, having a sedentary lifestyle, aging, having diabetes mellitus, CVD, lipodystrophy etc. confers risk.
1) Insulin Resistance
This is caused by an incompletely understood defect in insulin action. The onset of insulin resistance is heralded by postprandial hyperinsulinemia, followed by fasting hyperinsulinemia and, ultimately, hyperglycemia.
2) Increased Waist Circumference
Waist circumference is an important component of the most recent and frequently applied diagnostic criteria for the metabolic syndrome. However, measuring waist circumference does not reliably distinguish increases in subcutaneous adipose tissue vs. visceral fat; this distinction requires CT or MRI.
Hypertriglyceridemia is an excellent marker of the insulin-resistant condition. The other major lipoprotein disturbance in the metabolic syndrome is a reduction in HDL cholesterol.
4) Glucose Intolerance
The defects in insulin action lead to impaired suppression of glucose production by the liver and kidney and reduced glucose uptake and metabolism in insulin-sensitive tissues, i.e., muscle and adipose tissue. The metabolic syndrome is a fairly strong predictor of incident diabetes in many populations and that it predicts diabetes more strongly than it predicts coronary heart disease events.
The relationship between insulin resistance and hypertension is well established.
6) Proinflammatory Cytokines
Symptoms and Signs
The metabolic syndrome is typically not associated with symptoms! On physical examination, waist circumference may be expanded and blood pressure elevated. The presence of one or either of these signs should alert the clinician to search for other biochemical abnormalities that may be associated with the metabolic syndrome. Less frequently, lipoatrophy or acanthosis nigricans is found on examination.
The diagnosis of the metabolic syndrome relies on satisfying the criteria listed in Table 1 by using tools at the bedside and in the laboratory. The medical history should include evaluation of symptoms for OSA in all patients and PCOS in premenopausal women. Family history will help determine risk for CVD and DM. Blood pressure and waist circumference measurements provide information necessary for the diagnosis.
Fasting lipids and glucose are needed to determine if the metabolic syndrome is present. The measurement of additional biomarkers associated with insulin resistance can be individualized. Such tests might include apoB, high-sensitivity CRP, fibrinogen, uric acid, urinary microalbumin, and liver function tests. A sleep study should be performed if symptoms of OSA are present. If PCOS is suspected on the basis of clinical features and anovulation, testosterone, luteinizing hormone, and follicle-stimulating hormone should be measured.
Treatment: The Metabolic Syndrome
Obesity is the driving force behind the metabolic syndrome. In general, recommendations for weight loss include a combination of caloric restriction, increased physical activity, and behavior modification.
A high-quality diet— i.e., enriched in fruits, vegetables, whole grains, lean poultry, and fish—should be encouraged to provide the maximum overall health benefit.
Although increases in physical activity can lead to modest weight reduction, 60–90 min of daily activity is required to achieve this goal.
In some patients with the metabolic syndrome, treatment options need to extend beyond lifestyle intervention. Weight-loss drugs come in two major classes: appetite suppressants and absorption inhibitors. Bariatric surgery is an option for patients with the metabolic syndrome who have a body mass index (BMI) >40 kg/m2 or >35 kg/m2 with comorbidities. Gastric bypass results in a dramatic weight reduction and improvement in the features of metabolic syndrome. A survival benefit has also been realized.
For patients with the metabolic syndrome without diabetes, the Framingham risk score may predict a 10-year CVD risk that exceeds 20%. In these subjects, LDL cholesterol should also be reduced to <100 mg/dL. With a 10-year risk of <20%, however, the targeted LDL cholesterol goal is <130 mg/dL. Also refer to the newly instituted ASCVD calculator!
A fasting triglyceride value of <150 mg/dL is recommended. In general, the response of fasting triglycerides relates to the amount of weight reduction achieved. A weight reduction of >10% is necessary to lower fasting triglycerides.
++A fibrate (gemfibrozil or fenofibrate) is the drug of choice to lower fasting triglycerides and typically achieve a 35–50% reduction.
++Other drugs that lower triglycerides include statins, nicotinic acid, and high doses of omega-3 fatty acids.
Beyond weight reduction, there are very few lipid-modifying compounds that increase HDL cholesterol. Nicotinic acid is the only currently available drug with predictable HDL cholesterol-raising properties. The response is dose-related and can increase HDL cholesterol ~30% above baseline.
The direct relationship between blood pressure and all-cause mortality rate has been well established, including patients with hypertension (>140/90) versus prehypertension (>120/80 but <140/90) versus individuals with normal blood pressure (<120/80). In patients with the metabolic syndrome without diabetes, the best choice for the first antihypertensive should usually be an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker, as these two classes of drugs appear to reduce the incidence of new-onset Type 2 diabetes. In all patients with hypertension, a sodium-restricted diet enriched in fruits and vegetables and low-fat dairy products should be advocated. Home monitoring of blood pressure may assist in maintaining good blood pressure control.
Impaired Fasting Glucose
In patients with the metabolic syndrome and Type 2 diabetes, aggressive glycemic control may favorably modify fasting triglycerides and/or HDL cholesterol. Metformin has also been shown to reduce the incidence of diabetes, although the effect was less than that seen with lifestyle intervention.
Several drug classes [biguanides, thiazolidinediones (TZDs)] increase insulin sensitivity. Because insulin resistance is the primary pathophysiologic mechanism for the metabolic syndrome, representative drugs in these classes reduce its prevalence.
So do you think you/someone you know may have the metabolic syndrome? If so, contact your primary care doctor/cardiologist/your friendly neighborhood endocrinologist!!
1) Metabolic Syndrome and Incident Diabetes: Diabetes Care. 2008 Sep; 31(9): 1898–1904.
2) The Metabolic Syndrome: Harrison’s Endocrinology 3rd edition 2013 Chapter 18 253-260.