Metabolic syndrome (MetS) is a cluster of metabolic and cardiovascular (CV) risk factors, including visceral adiposity, hyperglycemia, dyslipidemia and hypertension, contributing to CV mortality. At the origin of MetS lies a common pathophysiology: insulin resistance. Despite major advances in prevention research, cardiovascular disease (CVD) remains the leading global cause of mortality.


Traditional Metabolic Syndrome Diagnosis Criteria

Although the specifics of various international diagnostic criteria may vary, providers typically must identify three out of five classic CV risk factors to confirm a diagnosis of MetS. Due to the ongoing global obesity epidemic, we often find that patients easily meet the criteria for a high BMI or enlarged waist circumference (AKA visceral adiposity).

This excess fat often initiates an inflammatory cascade that causes abnormal blood sugar, lipids or blood pressure, depending on a patient’s unique genetic predispositions, psychologic and physiologic stressors, and accumulated environmental toxin burdens. Having said all this, you’ve likely come across a patient who seems to have lived a relatively “clean” life and practiced a “healthy” lifestyle yet still meets MetS diagnostic criteria. How does this happen?


Diagnosing Non-Traditional Metabolic Syndrome

To evaluate this clinical paradox, let’s assume insulin resistance is still the probable driving dysfunction of the patient’s MetS. Additionally, we may infer that some unfavorable set of inflammatory triggers or toxins is driving this insulin resistance. Logically, the next step would be to identify and address those factors to reduce the signals promoting insulin resistance. Since inflammation has countless sources, the real partnership goal is to discover the ones unique to the patient.

The goal is to expand your MetS paradigm so you can increase your odds of identifying those at risk. If we wait for a patient’s fasting glucose or triglycerides to go above some number, we may be solving a population health issue but not a personal health issue. Microvascular damage has likely been going on for five to 10 years by the time someone finally meets the criteria of MetS, meaning the kidneys, eyes, coronary microcirculation and many more systems have been under inflammatory attack for far too long.

Alternatively, consider identifying and addressing the clinical imbalances that come months and years before the typical MetS diagnosis is made. Once you see these ominous pathways already expressing themselves in your patient’s body and life, you and the patient can intervene proactively and powerfully.


Four Non-Traditional Warning Signs

1. Mental Health

Surprisingly, CVD is the one of the most common causes of mortality in schizophrenia, accounting for approximately one-third of all patient deaths.1 CVD is surpassed only by suicide in this population. Sadly, estimates indicate dyslipidemia, hypertension, obesity and type 2 diabetes occur in patients with schizophrenia and other serious mental illnesses at rates 1.5-2 times that of the general population.

From a functional medicine perspective, we should ask ourselves why this is so, especially if the patient is dealing with a mental health issue as part of their complex comorbidity condition set. Be curious with your patient about what factors may be driving their inflammation, including:

  • Abnormal sleep
  • Increased HPA axis activation
  • High glycemic impact foods
  • Side effects from atypical antipsychotics
  • Nutrient deficiencies from prescription drugs
  • Sedentary behavior
  • Social isolation


2. Irritable Bowel Syndrome

Many of us see patients with irritable bowel syndrome (IBS) who turn to functional medicine because they are dissatisfied with the conventional prescription approach. This condition commonly alters food choices, digestive capacity, nutrient absorption and elimination function, which are all vital to the prevention and treatment of MetS. Studies suggest IBS is significantly related to a higher prevalence of MetS and elevated triglycerides among adults; therefore, treating IBS may help prevent MetS.

But what connects these two seemingly disparate conditions from a systems biology approach? Consider that IBS may be linked to some form of gut dysfunction or inflammation. In that case, we would explore whether the causes of the IBS symptoms are all stemming from the gut directly (e.g., dysbiosis with or without resultant metabolic endotoxemia) or somewhere else (e.g., abnormal HPA axis and inflammatory cytokines affecting tight junctions in the gut lumen or poor oral health seeding the microbiome).

No matter the cause, it is essential to resolve the gut inflammation and dysfunction in these patients while scanning the body for more root causes or downstream inflammatory damage, such as MetS. Resolving gut inflammation is essential to resolving MetS.


3. Gluten-Free Dietary Choices

On a related note, patients with celiac disease are at high risk of developing MetS and non-alcoholic fatty liver disease (NAFLD), an increasingly common downstream effect of insulin resistance. Studies suggest that patients with celiac disease have a three-fold higher risk of developing NAFLD and a higher risk of developing CVD.

One study hypothesized that the root cause of MetS in those with celiac disease was connected to the gluten-free diet. As we know, “going gluten-free” can easily be misunderstood by patients as innately healthy. Unfortunately, many convenient gluten-free substitutes have high glycemic indexes and are proinflammatory. Here, we have an opportunity to guide celiac and non-celiac, gluten-sensitive patients to nourish wisely so they may gain the benefits of gluten elimination while preventing the risks of highly processed, high glycemic substitutes.

We can also guide celiac patients to the well-researched, anti-inflammatory Mediterranean-based diet, which is rich in healthy gluten-free carbohydrate options. To be complete, the Mediterranean diet is part of a well-balanced, anti-inflammatory Mediterranean lifestyle, including regular physical activity and a sense of community and purpose. These personalized lifestyle choices are powerful components of the cumulative anti-inflammatory signaling we should emphasize and promote to all patients.


4. Autoimmune Disease

You may have recently noticed great interest in the interface between the metabolic and immune systems. We are learning these interactions are regulated through genetics, nutritional status and the gut microbiome. We also know that unhealthy immune-metabolic crosstalk contributes to the development of autoimmune diseases.

Some of this crosstalk is linked to adipose tissue. Adipokines are involved in numerous metabolic activities that contribute to the development of MetS. Increased occurrence of MetS is seen in patients with autoinflammatory diseases (e.g., gout) and autoimmune rheumatic diseases (ARD) (e.g., lupus and rheumatoid arthritis).2 Proinflammatory signaling pathways in ARD could also induce other markers of chronic inflammation that contribute to CVD. Unfortunately, CVD rates remain high despite recent advances in ARD treatment. MetS and proinflammatory adipokines could be the connection between CVD and ARD.



Final Thoughts

In review, we see that inflammation has many hidden faces, and this stealth inflammation spurs the insulin resistance that secretly drives the development of MetS. Be open to seeing the origins of MetS in all areas of the body. This holistic approach aligns with a commitment to patient care excellence and reducing the massive clinical, financial and social impacts of CVD.


Shilpa P. Saxena, MD, IFMCP is a board-certified family physician whose passion and purpose come to life through an uncompromising dedication to the ‘health’ and ‘care’ aspects of healthcare. Beyond continuing to practice as Medical Director of Forum Health Tampa, Dr. Saxena serves as Chief Medical Officer at Forum Health. In addition to over 15 years of progressive patient care, Dr. Saxena is Faculty with the Institute for Functional Medicine, as well as contributing faculty or physician educator roles with the Andrew Weil Center for Integrative Medicine, George Washington University’s Metabolic Medicine Institute, University of Miami Miller School of Medicine’s Department of Family Medicine and Community Health, and Universidad San Ignacio de Loyola (Lima, Perú). She joined the Lifestyle Matrix Resource Center team over 10 years ago to help providers, patients and practices around the world deliver effective shared medical appointments through her Group Visit Toolkits. She also continues to serve as the Clinical Expert for the CM Vitals Program. 



1. Riordan HJ, Antonini P, Murphy MF. Atypical antipsychotics and metabolic syndrome in patients with schizophrenia: risk factors, monitoring, and healthcare implications. Am Health Drug Benefits. 2011 Sep;4(5):292-302.
2. Medina G, Vera-Lastra O, Peralta-Amaro AL, Jiménez-Arellano MP, Saavedra MA, Cruz-Domínguez MP, Jara LJ. Metabolic syndrome, autoimmunity and rheumatic diseases. Pharmacol Res. 2018 Jul;133:277-288.