Metabolic Syndrome (MetS): Symptoms, Causes, Diagnostic Testing, Treatment

Metabolic syndrome (MetS) is a multifactorial pathological condition characterized by the coexistence of metabolic disturbances such as central obesity, hypertension, dyslipidemia, and impaired glycemic homeostasis. It is not considered a distinct disease but rather a cluster of metabolic abnormalities that significantly increase the risk of developing cardiovascular diseases and type 2 diabetes.

Early recognition and management of metabolic syndrome are particularly important, as it is a progressive condition that can often be prevented, or even reversed, through a combination of medical interventions, dietary adjustments, and lifestyle changes. The functional medicine approach not only facilitates diagnosis but also enables a deeper investigation of underlying causes, supporting the development of personalized therapeutic strategies.

Epidemiological Data

Metabolic syndrome has reached the scale of a global epidemic. According to the World Health Organization, it affects approximately 25% of the adult population worldwide. Its prevalence increases with age and is particularly higher among middle-aged men and postmenopausal women.

In Greece, recent epidemiological studies (e.g., ATTICA and MEDIS) indicate that the proportion of the population affected by metabolic syndrome ranges from 20% to 40%, depending on gender, age group, and geographic region. Contributing factors include adopting a Western lifestyle, physical inactivity, and a diet high in processed carbohydrates.

At the same time, the rise in childhood obesity in Greece is an additional cause for concern, as it predisposes individuals to metabolic syndrome as early as adolescence.

Symptoms and Signs of MetS

Metabolic syndrome often does not present with prominent or specific symptoms in its early stages, making diagnosis difficult without laboratory testing. However, careful clinical observation may reveal a range of signs and indications which, when combined with test results, support a more accurate diagnosis. Common signs and symptoms include:

Increased abdominal fat (central/visceral obesity): Excess fat accumulation around the abdomen is a key feature. Waist circumference of 102 cm or more in men and 88 cm or more in women indicates increased risk.
Elevated blood pressure: Systolic ≥130 mmHg or diastolic ≥85 mmHg, or the need for antihypertensive therapy. Patients may experience headaches, dizziness, fatigue, or may be asymptomatic.
Dyslipidemia: High triglycerides (>150 mg/dL) and low HDL cholesterol (<40 mg/dL in men, <50 mg/dL in women). These are typically silent abnormalities but may be associated with fatigue or cardiovascular risk.
Hyperglycemia: Fasting glucose ≥100 mg/dL or the presence of type 2 diabetes. May be accompanied by frequent urination, excessive thirst, dry mouth, and unexplained weight changes.
Insulin resistance: Often asymptomatic, associated with elevated insulin levels and pancreatic strain. Considered a hidden but central driver of the syndrome.
Skin changes: Thickening and darkening of skin folds, especially on the neck, underarms, or groin -an indicator of insulin resistance.
Fatigue and reduced endurance: Resulting from metabolic imbalance and low cellular energy output.

Metabolic syndrome is not a static condition but a progressively worsening metabolic imbalance. The appearance, and especially the combination of these signs, should prompt more extensive investigation using both standard and functional diagnostic methods.

Deeper Causes of MetS

Metabolic syndrome is not caused by a single factor but is the result of a complex interaction of genetic, environmental, and metabolic influences. Understanding these underlying causes is essential for prevention and for effective, personalized therapeutic intervention.

Insulin resistance is the central pathophysiological mechanism. It refers to a condition in which the body’s cells, particularly muscle, adipose, and liver cells, do not respond adequately to insulin, leading to increased production by the pancreas. Chronic hyperinsulinemia promotes fat storage, inflammation, and disruption of glycemic balance.
Central obesity and visceral fat: The accumulation of adipose tissue around the abdomen and internal organs leads to increased secretion of pro-inflammatory cytokines (such as TNF-α and IL-6) and free fatty acids, which contribute to insulin resistance. Visceral fat acts not only as an energy reservoir but also as an endocrine organ that affects systemic homeostasis.
Chronic low-grade inflammation: Individuals with metabolic syndrome often present subclinical inflammation that is not clinically perceptible but can be detected through laboratory tests (e.g., elevated CRP, IL-6, TNF-α). This inflammation negatively affects insulin sensitivity, damages endothelial cells, and promotes atherogenesis.
Gut microbiome dysregulation: The gut microbial population plays a crucial role in nutrient absorption, immune regulation, and metabolism of fats and sugars. Dysbiosis, the imbalance of this microbial population, has been associated with increased intestinal permeability (“leaky gut”), inflammation, and metabolic disturbances.
Hormonal imbalances: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, hyperinsulinemia, thyroid dysfunction, or elevated cortisol levels due to chronic stress can all affect fat storage, insulin sensitivity, and general metabolic function.
High-glycemic dietary patterns: Excessive consumption of simple carbohydrates, processed foods, and trans fats leads to frequent fluctuations in blood sugar, increased insulin secretion, and long-term dysfunction of pancreatic β-cells. At the same time, diets low in fiber and antioxidants fail to protect the body against inflammation and oxidative stress.
Genetic predisposition: Although heredity is not the determining factor, certain genetic polymorphisms are associated with an increased risk of developing metabolic syndrome. This genetic predisposition tends to manifest more strongly when combined with an unhealthy lifestyle.

Diagnostic Testing for MetS

The timely and accurate diagnosis of metabolic syndrome requires a comprehensive laboratory evaluation, utilizing both conventional diagnostic tests and imaging methods, as well as specialized laboratory analyses rooted in functional medicine.

(a) Conventional Laboratory Tests

Basic laboratory tests are widely used to diagnose the criteria for metabolic syndrome and to monitor overall metabolic health.

Insulin Resistance Panel: Includes the following:
- Fasting glucose: Measures blood glucose levels after 8–12 hours of fasting. Values ≥100 mg/dL indicate a predisposition to type 2 diabetes.
- Fasting insulin: Detects elevated insulin levels that suggest insulin resistance, even when glucose is within the normal range.
- HOMA-IR index: Calculated using fasting glucose and insulin levels. Values >2.5 are considered suspicious for insulin resistance.
Glucose and/or Insulin Tolerance Test: Provides a detailed profile of glycemic and insulinemic response after glucose ingestion.
Total Cholesterol (TC): Assesses the total amount of cholesterol in the blood, including LDL, HDL, and VLDL. It offers a general estimation of cardiovascular risk.
HDL Cholesterol (High-Density Lipoprotein): Often referred to as “good” cholesterol. Low levels (<40 mg/dL in men, <50 mg/dL in women) are diagnostic for metabolic syndrome.
Triglycerides: Elevated levels (>150 mg/dL) are associated with insulin resistance and an increased risk of coronary artery disease.
High-Sensitivity C-Reactive Protein (hs-CRP): A marker of low-grade chronic inflammation. Elevated values are linked to increased cardiometabolic risk and are ideal for early detection of inflammatory background.

(b) Functional Medicine Tests

These tests are designed to detect dysfunctions before the onset of overt disease and support a personalized approach to health:

Adiponectin and Leptin: Biomarkers related to obesity, insulin sensitivity, and systemic inflammatory tone.
Adrenal Function – AdrenalScan® (HormoneScan®): Measures cortisol and DHEA-S levels to assess the hypothalamic–pituitary–adrenal (HPA) axis. Chronic imbalances are associated with insulin resistance, increased visceral fat, and persistent inflammation.
Gut Microbiome – EnteroScan®: Analyzes the composition and functionality of the intestinal microbiota, the presence of pathogens, and inflammatory activity. It is closely linked to the development of metabolic disorders.
Oxidative Stress – DetoxScan®: Evaluates the body’s antioxidant defense system and the presence of oxidative damage caused by free radicals. Oxidative stress is a key contributor to insulin resistance.
Urine Metabolomic Analysis – MetaBolomiX™: Identifies metabolic dysfunctions such as impaired cellular energy production, detoxification capacity, and nutritional deficiencies.

Blood Pressure: Although not a laboratory test, regular monitoring is essential. Readings ≥130/85 mmHg warrant further investigation.
Carotid Artery Triplex Ultrasound: Assesses atherosclerotic plaque formation and intima-media thickness.
Upper Abdominal Ultrasound: Evaluates the liver for fatty infiltration, such as in non-alcoholic fatty liver disease (NAFLD).
Visceral Fat DEXA Scan: Provides a precise measurement of total and specifically visceral fat tissue.

Therapeutic Approaches for MetS

The treatment of metabolic syndrome is not based on a single approach, but rather on a holistic intervention model that includes both conventional (pharmaceutical) and natural therapies. The primary goals are to modify risk factors, improve metabolic markers, and prevent complications such as diabetes and cardiovascular disease.

(a) Conventional Therapies

Pharmacological interventions are an important tool when lifestyle changes are insufficient or when metabolic parameters are already significantly impaired. These include antihypertensive medications, such as ACE inhibitors, ARBs, and diuretics, selected based on coexisting conditions (e.g., kidney dysfunction or heart failure). Statins and fibrates are used in cases of dyslipidemia, such as elevated triglycerides or low HDL, with statins offering additional anti-inflammatory effects. Antidiabetic agents like metformin are commonly recommended for patients with insulin resistance or prediabetes. Lastly, low-dose aspirin may be prescribed preventively for individuals at high cardiovascular risk. All such interventions must be administered under medical supervision and tailored to each individual’s needs and clinical profile.

(b) Natural Therapies and Holistic Management

The root of the problem in metabolic syndrome is often functional and nutritional. Therefore, natural interventions aim to restore cellular function and support overall homeostasis.

Nutrition forms the foundation of the therapeutic approach. Key principles include:

Reducing glycemic load: Avoid processed carbohydrates and sugars. Emphasize foods with a low glycemic index (such as legumes, vegetables, oats).
Increasing dietary fiber: Fiber improves insulin sensitivity and reduces inflammation by supporting the gut microbiome.
High-quality fats: Increase intake of omega-3 fatty acids (from fatty fish, flaxseeds, walnuts) and avoid trans fats.
Intermittent fasting: Has been shown to improve insulin sensitivity, support weight loss, and activate cellular autophagy.

Overall lifestyle improvement is essential for long-term management.

Exercise: Regular aerobic activity (30–45 minutes daily) combined with resistance training enhances mitochondrial function, reduces visceral fat, and increases insulin sensitivity.
Stress management: Techniques such as meditation, yoga, light physical activity, and improved sleep help regulate the neuroendocrine axis and reduce inflammation.

Supplements and herbal therapies serve as supportive interventions in the management of metabolic syndrome, aiming to improve insulin sensitivity, regulate inflammation, and promote metabolic balance. Inositol (Myo- and D-Chiro-) is mainly used in cases of insulin resistance, particularly in women with polycystic ovary syndrome. Vitamin D3 is essential for glucose regulation and insulin function. Omega-3 fatty acids (EPA and DHA) offer cardioprotective and anti-inflammatory benefits. Berberine is a plant-derived compound with glucose-regulating and metabolism-enhancing properties. Polyphenols such as curcumin and resveratrol exert antioxidant and anti-inflammatory effects, supporting overall metabolic health. The use of these supplements should always be guided by medical supervision and individualized assessment to avoid potential side effects, interactions, or inappropriate dosing.

Conclusions

Metabolic syndrome (MetS) is a complex condition with serious health implications, yet it can often be prevented or effectively managed. Timely diagnosis and a deep understanding of its root causes, such as insulin resistance, inflammation, and hormonal imbalances, are critical. Functional medicine emerges as a valuable approach, offering targeted testing and personalized interventions that focus not only on treatment but also on prevention through the early detection of metabolic imbalances.

Literature

Giacco A, Cioffi F, Silvestri E. Mediterranean Diet and Metabolic Syndrome. Nutrients. 2025;17(14):2364. Published 2025 Jul 18. doi:10.3390/nu17142364
Prabhu GS, Concessao PL. Triglycerides and metabolic syndrome: from basic to mechanism - A narrative review. Arch Physiol Biochem. 2025;131(3):342-350. doi:10.1080/13813455.2024.2426496
Kastorini, C.-M., Panagiotakos, D. B., Georgousopoulou, E. N., Laskaris, A., Skourlis, N., Zana, A., Chatzinikolaou, C., Chrysohoou, C., Puddu, P. E., Tousoulis, D., Stefanadis, C., & Pitsavos, C. (2016). Metabolic syndrome and 10-year cardiovascular disease incidence: The ATTICA study. Nutrition, Metabolism and Cardiovascular Diseases, 26(3), 223–231. https://doi.org/10.1016/j.numecd.2015.12.010
Anastasaki, M., Papadakis, S., Linardakis, M., Anyfantakis, D., Symvoulakis, E. K., & Lionis, C. (2020). Burden of metabolic syndrome among primary care patients in Crete, Greece: A descriptive study. European Journal of General Practice, 26(1), 166–174. https://doi.org/10.1080/13814788.2020.1851676
Tyrovolas S, Chalkias C, Morena M, Tsiligianni I, Zeimbekis A, Gotsis E, Metallinos G, Bountziouka V, Polychronopoulos E, Lionis C, Panagiotakos D. Health care access and prevalence of the metabolic syndrome among elders living in high-altitude areas of the Mediterranean islands: the MEDIS study. Rev Diabet Stud. 2011 Winter;8(4):468-76. doi: 10.1900/RDS.2011.8.468. Epub 2012 Feb 10. PMID: 22580728; PMCID: PMC3359691.
Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis. 2017;11(8):215-225. doi:10.1177/1753944717711379
Zheng L, Zeng A, Liu L, et al. Metabolic syndrome: molecular mechanisms and therapeutic interventions. Mol Biomed. 2025;6(1):59. Published 2025 Aug 26. doi:10.1186/s43556-025-00303-5
Theodorakis N, Nikolaou M. From Cardiovascular-Kidney-Metabolic Syndrome to Cardiovascular-Renal-Hepatic-Metabolic Syndrome: Proposing an Expanded Framework. Biomolecules. 2025;15(2):213. Published 2025 Feb 2. doi:10.3390/biom15020213

At Diagnostiki Athinon, we treat prevention with the seriousness it deserves. This is where science meets personalized care.