The National Cholesterol Education Program-Adult Treatment Panel III outlined five criteria for diagnosing metabolic syndrome. The five criteria for diagnosis included waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, and insulin resistance.
Metabolic syndrome is diagnosed when a patient has three or more of these five signs: a large waistline (abdominal obesity), high blood pressure, high fasting blood sugar, high triglycerides, and low HDL (“good”) cholesterol, which significantly increases the risk for heart disease, stroke, and type 2 diabetes. A combination of laboratory tests and a physical examination is used to diagnose metabolic syndrome. The criteria for abdominal obesity are a waist circumference of 40 inches for men and 35 inches for women. The metabolic syndrome blood pressure criterion is greater than 130/85 mmHg. A normal blood pressure is 120/80. High blood sugar symptoms are blurred vision, increased thirst, increased urination, tiredness, and weakness. A fasting blood glucose level of 100 mg/dL or higher indicates insulin resistance.
Triglycerides are the main type of fat in the body, which become elevated due to excess calories, fats, and sugar consumed in food. Triglycerides circulate in the blood to provide energy for tissues. Excess triglycerides are stored in fat cells. High levels of triglycerides, over 150 mg/dL, are linked to heart disease, stroke, and pancreatitis. The metabolic syndrome criteria for low HDL cholesterol (good cholesterol) are below 40 mg/dL for men and below 50 mg/dL for women.
Risk factors that can be controlled in metabolic syndrome are diet, exercise, sleep, smoking, and excessive alcohol intake. Shift work has also been studied as a risk factor for metabolic syndrome. Risk factors that cannot be controlled that may lead to metabolic syndrome include older age, with females having a higher rate of metabolic syndrome than men, a history of diabetes, obesity, psoriasis, and obstructive sleep apnea. Metabolic syndrome prevalence significantly increases with age, affecting approximately 19.5% of adults aged 20–39 and rising to nearly 50% (48.6%) in those aged 60 years and older. While most common in older adults, it affects individuals across all age groups, with a significant risk in those aged 40–59.
Medications for allergies, bipolar disease, schizophrenia, depression, and HIV have played a role in increasing the risk of metabolic syndrome. Examples of medications that may lead to metabolic syndrome include prednisone, a corticosteroid prescribed as an anti-inflammatory medication for asthma and COPD exacerbations, allergic reactions, and inflammatory bowel disease. Prednisone may also increase abdominal fat and blood sugar levels. Citalopram (Celexa) and escitalopram (Lexapro) are serotonin reuptake inhibitors (SSRIs) prescribed for depression. SSRIs may also increase waist circumference, weight, and blood lipids.
Diet and exercise play a significant role in controlling metabolic syndrome. A diet for patients with metabolic syndrome focuses on reversing insulin resistance, lowering blood pressure, and reducing cholesterol by emphasizing high-fiber, plant-based, nutrient-dense foods. Key components include consuming vegetables, fruits, whole grains, and lean proteins while limiting saturated fats, added sugars, sodium, and processed foods. The DASH and Mediterranean diets are highly recommended. The DASH diet (Dietary Approaches to Stop Hypertension) and the Mediterranean diet are both heart-healthy, flexible eating plans designed to lower blood pressure and cholesterol by emphasizing nutrient-rich, whole foods. They restrict sodium (typically <2,300mg/day, with an aggressive 1,500mg/day goal), added sugars, and saturated fats, while promoting fruits, vegetables, whole grains, and lean proteins. Exercising, as recommended by the American Heart Association (AHA), for 150 minutes per week has been shown to control and decrease metabolic syndrome risk factors.
Medication treatment of metabolic syndrome aims to control weight, insulin resistance, and dyslipidemia (low HDL and high triglycerides), reduce cardiovascular risk, and treat prediabetes/diabetes.
Weight-loss medications recommended by the guidelines include liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy). Liraglutide and semaglutide are GLP-1 (glucagon-like peptide-1) receptor agonists indicated for type 2 diabetes, weight loss, and the treatment of comorbid metabolic syndrome. Studies and guidelines recommend GLP-1 receptor agonists to reduce the severity of metabolic syndrome (Cardiovasc Diabetol 2023 Feb 25;22(1):41). The mechanism of action for the GLP-1 receptor agonists is the promotion of weight loss by mimicking the GLP-1 hormone to suppress appetite, increase feelings of fullness, and slow gastric emptying. Stimulating GLP-1 causes insulin release when blood glucose levels are high. Metformin is prescribed to manage prediabetes and insulin resistance. Prediabetes is a condition where blood sugar levels are higher than normal (100–125 mg/dL fasting) but not high enough for a type 2 diabetes diagnosis. Key risk factors include being over 45, overweight, and inactive. Metformin’s mechanism of action is to lower blood glucose primarily by inhibiting hepatic (liver) glucose production. It also decreases intestinal glucose absorption and improves insulin sensitivity by enhancing peripheral glucose uptake and utilization. Metformin may also manifest a weight loss of 4-11 pounds over a 6–12-month period.
For glucose intolerance, SGLT-2 Inhibitors (SGLT2I) and GLP-1 receptor agonists are prescribed for their beneficial effects on weight loss and cardiovascular risk reduction. Empagliflozin (Jardiance) and dapagliflozin (Farxiga) are SGLT2 inhibitors indicated for the management of key components of metabolic syndrome, including type 2 diabetes, obesity, hypertension, and high triglycerides. SGLT2 inhibitors can improve glycemic control, promote weight loss, lower blood pressure, and reduce cardiovascular/renal risk.
The primary treatment for dyslipidemia (high LDL-C, low HDL, and high triglycerides)observed in metabolic syndrome is statins. The two most studied statins in dyslipidemia are atorvastatin (Lipitor) and rosuvastatin (Crestor). Rosuvastatin is generally recognized as the most effective statin for simultaneously lowering triglycerides (TG) and increasing high-density lipoprotein (HDL) cholesterol, often outperforming atorvastatin (Lipitor) in head-to-head trials (Stellar Trial, Am J Cardio 2003;92:152-60). The mechanism of action of statins is by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis. Fibrates and fish oil may be prescribed to lower triglyceride levels and raise HDL. Fenofibrate (Tricor) is the primary recommended fibrate, often combined with Lovaza or Vascepa (omega-3-acid ethyl esters).
ACE inhibitors (Lisinopril and Ramipril) and angiotensin receptor blockers (Losartan and Candesartan) are prescribed when patients with metabolic syndrome have hypertension with diabetes. ACE inhibitors and angiotensin receptor blockers have been shown to reduce cardiovascular events and protect the kidneys.
Patients with metabolic syndrome face a roughly 2-fold increased risk of cardiovascular disease and a 5-fold higher risk of type 2 diabetes compared to those without metabolic syndrome. Diabetes causes nephropathy (kidney damage), neuropathy (nerve damage), and retinopathy (eye damage). Cardiovascular diseases include heart attacks and strokes. If caught early, losing 7% of body weight and exercising 150 minutes a week can decrease the prevalence of the syndrome by 43% to 51% (J Am Coll Cardiol. 2024; doi: 10.1016/j.jacc.2023.12.019). Early intervention significantly reduces the 30% higher risk of death and prevents premature heart attacks or strokes associated with untreated, long-term metabolic syndrome. Be well and fly safe.
