Metabolic Syndrome: Understanding, Managing, and Thriving

Welcome to our blog, where we dive deep into the intricate world of metabolic syndrome, shedding light on its risk factors, underlying causes, clinical features, and effective management strategies. Whether you're navigating this syndrome yourself or seeking knowledge for a loved one, this comprehensive guide aims to provide clarity and actionable insights.

Understanding Metabolic Syndrome: The Silent Culprit

Metabolic syndrome, also known as Syndrome X or insulin resistance syndrome, is a cluster of metabolic abnormalities that significantly increase the risk of cardiovascular diseases (CVD) and diabetes mellitus.

Diagnostic Criteria

NCEP: ATP 3 and Harmonizing definitions outline key parameters, including central obesity, hypertriglyceridemia, low HDL cholesterol, hypertension, and fasting plasma glucose.

Also Read: Acromegaly- Clinical Features, Diagnosis, Treatment

Risk Factors: Decoding the Contributors

Obesity and Sedentary Lifestyle

Explore the critical role of central adiposity, sedentary habits, and genetic predispositions in the development of metabolic syndrome.

Age and Diabetes Connection

Understand how age, particularly over 60 years, and the presence of diabetes mellitus amplify the risk.

Also Read: Management of Inflammatory Bowel Disease (Ulcerative Colitis and Crohn's Disease) 

Etiology: Unraveling the Insulin Resistance Enigma

Insulin Resistance: The Core Mechanism

Delve into the most accepted hypothesis - insulin resistance, examining its onset, impact on fatty acid metabolism, and subsequent contributions to metabolic abnormalities.

Fatty Acid Effects and Inflammation

Examine how excess fatty acids, inflammation, and proinflammatory cytokines exacerbate insulin resistance, leading to a cascade of metabolic dysregulation.

Clinical Features: The Subtle Signs

Physical Examination

Learn about the subtle signs clinicians look for, including increased waist circumference and elevated blood pressure, often accompanied by cutaneous manifestations like lipodystrophy and acanthosis nigricans.

Increased Waist Circumference

One of the key clinical features is central obesity, often measured by an increased waist circumference. This visceral fat accumulation is a subtle but crucial indicator of metabolic disturbances.

Elevated Blood Pressure

Metabolic Syndrome is frequently associated with hypertension. Understanding the intricate relationship between insulin resistance and blood pressure regulation is essential for early detection.

Acanthosis Nigricans and Lipodystrophy

Subtle skin manifestations like Acanthosis Nigricans and Lipodystrophy may serve as visible markers of insulin resistance, prompting clinicians to explore deeper into metabolic health.

Diagnosis: Navigating the Criteria

1. NCEP: ATP 3 Criteria

• Central obesity (waist circumference)
• Hypertriglyceridemia
• Low HDL cholesterol
• Hypertension
• Fasting plasma glucose

2. Harmonizing Definition

• Adapted waist circumference for South Asian populations
• Presence of 3 out of 5 criteria indicates Metabolic Syndrome

3. Laboratory Tests

• Fasting lipids and glucose measurements
• Additional biomarkers like Apo B, hs CRP, and uric acid can provide a comprehensive picture.

Treatment Strategies: A Holistic Approach

 Lifestyle Modification

• Weight Reduction: Aim for a 5-10% reduction, which significantly improves insulin sensitivity.
• Dietary Changes: Embrace a high-quality diet rich in fruits, vegetables, and fish.
• Physical Activity: Regular exercise is a cornerstone for managing metabolic syndrome.

Moreover, there is concern about low-carbohydrate diets enriched in saturated fat with increased atherosclerotic cardiovascular disease. A high-quality dietary pattern rich in fruits, vegetables, grains, fish

Physical activity

Before prescribing a physical activity program to patients with the metabolic syndrome, it is important to ensure that the increased activity does not incur risk. Some high-risk patients should undergo formal cardiovascular evaluation before the exercise program. For an inactive participant, gradual increases in physical activity should be encouraged to enhance adherence and avoid injury. Although increases in physical activity can lead to modest weight reduction: 60-90 mins (moderate-high intensity)

Even if an overweight or obese adult is unable to undertake this level of activity. Health benefit is seen if the activity is done for 30 mins (moderate intensity). Behavior modification Recommendation for dietary restriction and increased physical activity.

Obesity 

• Treatment options are extended beyond lifestyle intervention. Weight loss drugs: Appetite suppressants, Absorption inhibitors. Appetite suppressants approved by the U.S. Food and Drug Administration (FDA) include: - Phentermine (3 months). More Recent Additions Phentermine/Topiramate, Causes 8% weight loss. Seen in 50% of patients. S/E: Palpitations, headache, constipation, paresthesias, insomnia Naltrexone/Bupropion- Reduces 10% body weight. Contraindicated in seizure disorders and uncontrolled HTN. High-dose Liraglutide (3 mg), 6% weight loss is achieved. S/E: Nausea, vomiting. Semaglutide(2.4 mg weekly)-14.9% weight loss
• Orlistat inhibits the fat absorption by 30% Cause 4% of weight loss, Reduce incidence of T2DM, Oily leakage in rectum. Metabolic or Bariatric surgery: BMI>40 or >35 + comorbidities. Gastric bypass or vertical sleeve gastrectomy causes weight reduction.

LDL Cholesterol

• Patients aged 20-75 years with LDL cholesterol levels ≥190 mg/dL should take: Atorvastatin 40-80 mg, Rosuvastatin 20-40 mg. Patients with type 2 diabetes aged 40-75 years- Moderate dose is given. Atorvastatin 10-20mg, Rosuvastatin= 10 mg. A coronary calcium score is helpful in statin therapy. Normal: 0, Moderate: 100-300, Severe : >300 ( agatston score ). Diet is restricted in saturated fat and Trans fat. Statins(1st choice) in lowering LDL by 50-60%. Doubling: reduces the LDL by 6%. Ezetimibe(2nd choice)- cholesterol absorption inhibitor: Reduces the LDL by 15-20%
• Bempedoic acid alone or in combination with ezetimibe: 35% reduction of LDL. Increases plasma uric acid levels.PCSK9 inhibitors, potent LDL. cholesterol-lowering drugs, reduces LDL by 40-50%. Familial high cholesterolemia, used when other medications are not effective.- Bile acid sequestrants (cholestyramine, colestipol, and colesevelam) may be more effective than ezetimibe. Should not be given if, TG>300, causes gastrointestinal abnormalities. Nicotinic acid has similar LDL Cholesterol lowering capacity (<20%). Fenofibrate> gemfibrozil is used to reduce LDL.

Triglycerides

• Fasting triglycerides >500 mg/dL develops pancreatitis. Gemfibrozil or fenofibrate. (DOC) reduces by 30-40%. Concomitant administration of fibrates with drugs metabolized by the 3A4 cytochrome P450 system with statins, increased risk of myopathy. Other drugs: statins, nicotinic acids, omega-3 fatty Acids. Intermediate or high doses of "more potent" statins to lower TGS- Atorvastatin, Rosuvastatin. Nicotinic acid lowers fasting triglycerides: 20-35%, Increases FBS and contraindicated in Diabetes. Omega 3 fatty acids: EPA, DHA

        reduce Fasting TGs by 25-40%

HDL Cholesterol

• Nicotinic acid (increased HDL level) by 30% above the baseline, Statins, fibrates, and bile acid sequestrants (5-10%)
• After several trials of nicotinic acid versus placebo in statin-treated patients, there is no evidence that raising HDL cholesterol with nicotinic acid beneficially affects ASCVD events in patients with or without the metabolic syndrome.

Blood Pressure

• The direct relationship between blood pressure and all-cause mortality rate has been well established in studies comparing patients with (>140/90: high chances of mortality). In patients who have the metabolic syndrome without diabetes, the best choice of initial antihypertensive Drugs includes ACE inhibitors/ARBs. Additional agents: Calcium channel blockers, beta blockers, MRA (finerenone). Lifestyle modifications- Sodium restricted diet rich in fruits and vegetables, supplementation of whole grains, low fat diet

Impaired glucose control 

• In patients with metabolic syndrome and type 2 diabetes, aggressive glycemic control decrease triglyceride levels. Increase HDL. In patients with impaired fasting glucose who do not have diabetes, a lifestyle intervention that includes weight reduction, carbohydrate restricted diet and increased physical activity. Metformin reduces the incidence of diabetes and promotes weight loss.

Insulin resistance

• Drug classes increase insulin sensitivity Biguanides and Trizolidones. Both enhance the insulin action in the liver and suppress glucose production. TZDs improves insulin mediated glucose uptake within muscle and adipose tissue.
• In a meta-analysis of nine trials involving 12,026 participants, the TZD pioglitazone versus placebo was associated with reduction in ASCVD events in patients with insulin resistance (metabolic syndrome), prediabetes and type 2 diabetes. Adverse effects include. Weight gain, Bone fracture, CHF. Benefits are seen in NAFLD- Metformin: PCOS. Markers of inflammation.

Also Read: Special Considerations in Diabetes Mellitus

Hope you found this blog helpful for your NEET SS Endocrinology Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.