From Confusion to Clarity: Why Talk about Metabolic Syndrome
Inside: What causes metabolic syndrome? And why is metabolic syndrome important? It’s closely tied to inflammation and insulin resistance. And while many people aren’t even clear about the five signs that indicate metabolic syndrome, research is clear that it signals risk of cardiovascular disease, diabetes, and cancer. It’s a call to action that warrants attention.
As you watch the movie Titanic, you already know how it ends. Yet still, from that moment when an iceberg is sighted and the crew tries valiantly to change course and stay clear, your heart races and you inwardly cheer, “Come on, it might not be too late! You can do it!”
In a similar way, people may see hints of threats to their health — blood pressure consistently rising a few points… blood lipids or blood sugars creeping out of a healthy range — and overlook the significance of what’s going on beneath the surface of these changes.
Why should dietitians talk about Metabolic Syndrome?
It calls healthcare professionals and individual clients to look beyond the sometimes-modest rise in risk factors that are easily noted. It reminds us to consider the underlying problems and make a turn in lifestyle choices that could avert bigger problems that otherwise may lie ahead.
Key Take-Away Points
♦ What are the 5 signs of metabolic syndrome? Abnormalities in blood sugar, blood pressure, HDL-cholesterol, blood triglycerides, and waist size are the criteria that define metabolic syndrome. Waist size gets particularly complicated, because different standards may apply to different people.
♦ Research shows that metabolic syndrome is an important sign of increased risk of cardiovascular disease, type 2 diabetes, MASLD, and some forms of cancer.
♦ Several underlying conditions interact to cause metabolic syndrome, including chronic inflammation, insulin resistance, and specific types of body fat.
♦ All body fat does not pose the same risk. Lots of research is still investigating potential for metabolically healthy obesity. Meanwhile, it’s clear that metabolic syndrome with normal weight is a significant health risk.
♦ Metabolic syndrome can be reversed with lifestyle changes. Some people are more prone to store visceral fat and develop metabolic syndrome, so when the syndrome is reversed, it’s important to develop a lifestyle with protective choices that can continue long-term.
Metabolic Syndrome Is on the Rise and Overlooked
- Nearly half (47.3%) of U.S. adults now have metabolic syndrome, according to the American Heart Association. That’s significantly more than the 1 in 3 people prevalence over the past decade.
- Prevalence rises with age… but it’s common even in middle age. Rates remain relatively low in children, adolescents, and young adults. But metabolic syndrome is now found in almost 40% of U.S. adults ages 40 to 59. And it’s nearing 50% in people ages 60 and older.
- Yet public awareness and understanding seems to be limited. Healthcare providers, including primary care physicians, generally identify metabolic syndrome as a condition of concern – yet most say they lack the time and resources to address it with their patients.
Identification of Metabolic Syndrome represents a call to action… to address underlying lifestyle-related risk factors. ~ American Heart Association report
What Are the 5 Signs of Metabolic Syndrome?
Metabolic syndrome is diagnosed when any three of five specific risk factors are present.
You may see several different definitions that have been used over the years with slightly different criteria. But currently, the International Diabetes Federation; the National Heart, Lung and Blood Institute of the NIH; the American Heart Association; and several other U.S. and international organizations recommend what is called a harmonized definition of metabolic syndrome.
Here are the criteria as most commonly applied in the U.S.:
- Fasting blood sugar of 100 mg/dl or more, or using medical treatment to control blood sugar
- Systolic blood pressure of 130 mm Hg or higher, diastolic blood pressure of 85 mm Hg or higher, or taking medication for high blood pressure
- Low HDL (“good”) cholesterol (less than 40 mg/dl in men, less than 50 mg/dl in women)
- High blood triglycerides (150 mg/dl or more) or taking medication to reduce high triglycerides
- Waist size (greater than 40 inches (102 cm) in men or 35 inches (88 cm) in women) for people of most ancestries in the U.S. Other standards are recommended for people of certain ethnic backgrounds.
If you meet at least three of these criteria, you’ve got metabolic syndrome.
Questions about Defining Metabolic Syndrome: Challenges of Waist Size
Notice that metabolic syndrome is not based on whether someone is classified as having overweight or obesity (based on BMI or other criteria).
Excess body fat is often at the heart of the problems driving metabolic syndrome. But visceral fat within the abdomen in particular is what’s behind these metabolic changes.
Waist size is not a perfect measure of visceral fat, since increases in waist can also reflect subcutaneous fat there. But unless someone has had body imaging that identifies visceral fat as part of some medical testing, waist measure is considered the most accessible “proxy” for visceral fat. Criteria used by the World Health Organization (WHO) use waist:hip ratio or a diagnosis of obesity based on BMI.
The biggest variation among metabolic syndrome criteria involves waist size:
- Some definitions use tighter criteria for waist: at 37½ inches (94 cm) for men and 32 inches (80 cm) for women. Some researchers say these lower cut-points better identify people at risk in the general population, too.
- For people of Asian ancestry, 34-36 inches (85-90 cm) for men and 32-36 inches (80-90 cm) for women have been recommended because of the genetic tendency for greater visceral fat at any given waist size. Other recommended ethnicity-based thresholds for waist size include 36 inches (90 cm) and 31.5 inches (80 cm) for men and women, respectively, of South and Central American descent; and 37 inches (94 cm) and 31.5 inches (80 cm) for men and women, respectively, of Eastern Mediterranean, Middle Eastern, and Sub-Saharan African descent.
- According to the American Heart Association, currently recommended cut points may overestimate metabolic syndrome in U.S. Hispanic/Latina females, but no adjusted criteria from the above have yet been recommended.
Why is Metabolic Syndrome Important? Closeup on the Research
At first glance, meeting these criteria may seem “just a little” abnormal.
- Blood sugar elevation may indicate prediabetes, not diabetes.
- Rise in blood pressure may be categorized as Stage 1 hypertension… that doesn’t sound so bad, right?
- And although the elevation in triglycerides is high enough to indicate risk, it may not be high enough to warrant medication for some people.
But together, these provide a sign that the overall environment within the body is not healthy.
Research has long shown that for people with metabolic syndrome:
- Heart disease risk doubles – including risk of heart attack, stroke, CVD, and death from CVD.
- Type 2 diabetes risk is over four times higher.
- Metabolic dysfunction-associated steatotic liver disease is more likely in people with metabolic syndrome. MASLD is the new term for what’s previously been called nonalcoholic fatty liver disease (NAFLD) and then metabolic associated fatty liver disease (MAFLD). These terms refer to abnormal fat deposits in the liver (shown by imaging or liver biopsy) without excess alcohol consumption or other causes. Metabolic abnormalities behind MASLD and metabolic syndrome overlap so much, it’s not clear how each may be involved in promoting the other.
Although metabolic syndrome is sometimes considered as a have-it-or-don’t condition, research shows that the more criteria of metabolic syndrome you meet, the greater are the health risks.
Metabolic Syndrome in Cancer Risk and Survivorship: Flying Under the Radar?
Metabolic syndrome signals other risks that often get overlooked. Dietitians and other healthcare professionals know about the links of metabolic syndrome to cardiovascular disease and type 2 diabetes.
But metabolic syndrome also increases risk of cancer, and of cancer recurrence and cancer mortality.
That’s an example of why it’s important to consider the big picture of what’s going on in the body with metabolic syndrome, rather than focusing only on treating individual components like blood pressure or blood lipids.
- Risk of colorectal, endometrial, liver, pancreatic and postmenopausal breast cancers increases by 25% to more than 60% in people with metabolic syndrome.
- Prostate cancer risk may not increase in men with metabolic syndrome, but studies suggest they are more likely to develop aggressive tumors and experience biochemical recurrence.
- After a diagnosis of cancer, risk of post-surgical complications, recurrence and mortality is higher among people with metabolic syndrome. Aromatase inhibitor and androgen deprivation therapy hormonal treatments for breast and prostate cancers may increase development of metabolic syndrome and amplify the CVD risk it poses. – And among survivors of childhood cancers, metabolic syndrome is a common late effect (depending on type of cancer and treatment), often with years of latency before it is seen.
What Causes Metabolic Syndrome? Research Into the Top Culprits
Development of metabolic syndrome is complex. It seems to involve several factors interacting on a background of genetic tendencies.
Specific types of excess body fat play an essential role.
When calorie consumption outpaces calorie needs, eventually it can exceed the capacity for subcutaneous fat tissue (the fat right under the skin) to take up and store fatty acids.
Ectopic fat is body fat deposited within tissues where it’s not meant to be, such as the liver, pancreas, heart, and skeletal muscle.
Visceral fat is fat that builds up surrounding the heart and within the abdomen surrounding gastrointestinal organs.
As blood circulates out of visceral fat, it mostly travels via the portal vein directly to the liver. An influx of high levels of free fatty acids in the liver triggers several changes in liver metabolism that result in increased levels of circulating insulin (hyperinsulinemia), increased production of triglyceride-carrying VLDL lipoproteins, and continued production of glucose in the liver.
Inflammation’s Underlying Influence
As visceral fat expands, immune cells (macrophages) invade fat tissue, surrounding normal fat cells and secreting proteins called cytokines that promote inflammation. Inflammation in this microenvironment – the area right around a fat cell –can stimulate chronic, low-grade inflammation throughout the body. Blood tests such as C-reactive protein (hsCRP) and interleukin-6 (IL-6) are markers that measure inflammation that develops systemically.
- Artery stiffness can increase due to inflammation in blood vessels. This can raise blood pressure and make high blood pressure less responsive to medications aimed at controlling it.
- Cancer development is promoted by inflammation, as it triggers signaling pathways and gene expression that promote cancer cell growth.
- Free radical production and oxidative stress increase with inflammation. These free radicals can damage DNA, leading to changes in genes that regulate cell survival and proliferation and thus cancer development. Inflammation and oxidative stress also produce changes in insulin receptors on cells and signaling pathways within cells that blunt insulin signaling and lead to insulin resistance.
(This relationship with insulin resistance seems to be circular, since insulin resistance also promotes chronic inflammation.)
Insulin Resistance and Metabolic Syndrome: Key to the Looming Risks?
Insulin resistance occurs when muscle, fat, and liver cells don’t respond well to insulin.
- Blood sugar levels rise, so the pancreas secretes more insulin. Blood sugars may remain near-normal as long as the pancreas is able to keep secreting more insulin. The result: circulating insulin levels become higher than normal.
- Increased levels of free fatty acids increase liver production of triglycerides. High triglyceride levels secreted in VLDL lipoproteins increase risk of cardiovascular disease. Increased fat stored in the liver can lead to NAFLD (now known as MASLD) discussed above.
- Blood pressure also increases with insulin resistance, in part because of increased retention of sodium by the kidneys. What’s more, insulin resistance reduces nitric oxide availability in the lining of blood vessel walls (the endothelium). This reduces arteries’ ability to relax and dilate. This condition of endothelial dysfunction plays an important role in artery stiffness, high blood pressure and vascular aging.
- Although insulin resistance means that muscle, liver, and adipose cells don’t respond normally to insulin, increased levels of circulating insulin exert important effects. Increased insulin affects reproductive hormones (for example, increasing production of estrogen in postmenopausal women). It increases liver production of an important growth factor. And it exaggerates activation of signaling pathways within cells that promote cell growth and reproduction. The result of all these changes: enhanced signaling for cancer development.
Metabolically Healthy Obesity? What’s the Current Research?
Metabolic syndrome usually – but not always — occurs in people with a BMI classified as overweight or obesity.
- But not everyone with overweight or obesity exhibits these risk factors.
- And some people with a normal BMI have metabolic syndrome.
Visceral and ectopic fat — as discussed above – are a key element in cardiovascular and metabolic risk. Some people are more prone than others to store excess calories in these risk-related spots. Among different individuals, with the same total body fat, visceral fat may show 2- or 3-fold differences.
Metabolically Healthy Obesity (MHO) refers to a BMI of 30 or more without any of the four metabolic syndrome criteria other than increased waist size. According to recent data, of the 40.9% of U.S. adults classified with obesity:
- 6.6% met criteria for metabolically healthy obesity and
- 34.3% had metabolically unhealthy obesity (meaning they had at least one of the components of metabolic syndrome).
Emerging evidence offers potentially important insights.
Imaging technology using CT, MRI, and DEXA scans now make it possible to measure visceral fat separately from subcutaneous fat. This has made it possible to show that people of the same BMI can differ dramatically in visceral fat, subcutaneous fat, lean tissue, and bone. Routine use of these scans is not practical, however.
Waist circumference is recommended as a good proxy to identify people likely to have increased health risk because of large amounts of visceral fat, especially if blood triglycerides are also elevated. The challenge in using this is the inconsistency that can occur because of where and how some people take the measurement.
Waist:hip ratio is another measure that can identify people likely to have excess visceral fat and is a marker of increased risk of cardiovascular disease. However, some research suggests that it doesn’t identify excess visceral fat any better than a simple waist circumference measure.
Metabolically Healthy Obesity vs. Metabolic Obesity with Normal Weight
More research is needed to clarify the long-term implications of overweight and obesity in the context of normal levels of blood pressure, blood sugar, triglycerides and HDL.
>> Is waist size below the cut point that defines metabolic syndrome? Especially if it’s below the stricter cut point set by international standards for metabolic syndrome, it’s possible that people in this group (currently 6.6% of U.S. adults) aren’t at increased risk of heart disease and diabetes.
>>>> However, it’s not known what this means for cancer risk, and it doesn’t remove the risk of other conditions (such as urinary incontinence and some forms of arthritis) that stem from excess weight itself.
>>>> More research is needed to show whether the apparently lower health risks in this group remain, since some research suggests that the period of metabolic health may be temporary.
>> Does waist size exceed the criterion for metabolic syndrome? If so, even though other criteria of metabolic syndrome may not be met, without a special scan to measure types of body fat, it’s not known if the waist size reflects a large amount of subcutaneous fat (which is not associated with inflammation or insulin resistance)… or if excess visceral fat is present but has not yet resulted in identifiable risks like inflammation, insulin resistance, and fat deposits in the liver.
Metabolic obesity but normal BMI? Some people with a BMI categorized as healthy can have the markers of poor metabolic health associated with obesity, and they face greater health risks than people with similar BMI but without metabolic abnormalities. Metabolic syndrome in people with a normal BMI tends to occur with higher body fat percentage or greater distribution in visceral (rather than subcutaneous) fat tissue. Increased waist size reflects increased abdominal fat.
>> Multiple prospective cohort studies (observational studies that follow people over time) show poor health outcomes among people with metabolic syndrome despite a normal BMI. Compared to people who are metabolically healthy, those with metabolic syndrome, related metabolic abnormalities, or elevated waist circumference have from 7% increased risk to almost 4 times the risk of cardiovascular disease, type 2 diabetes, several forms of cancer (breast, colorectal, and others), and increased mortality rates (overall mortality, cancer mortality, and CVD mortality).
Can Metabolic Syndrome Be Reversed?
Essentially, yes.
All 5 components can change with changes in lifestyle. Medications also can correct these metabolic abnormalities. Technically, if medications are used to control component risk factors like blood pressure and blood sugar, that still meets criteria that define metabolic syndrome. 
In all cases, recommendations call for starting with lifestyle.
- Blood pressure in people with hypertension can be reduced by 20-25 mm Hg with a combination of lifestyle strategies, including a dietary pattern with foods that help lower blood pressure.
- Triglyceride levels that are high can drop 20 to 50 percent, or even more, with lifestyle changes. People can explore options to find the best way to lower triglycerides that works for them.
- Fasting blood sugar and HDL-cholesterol levels can improve with lifestyle changes that can fit in an individual lifestyle.
What about waist size?
- In people with excess visceral fat, modest changes in lifestyle can reduce levels more than people may realize. Including moderate physical activity has reduced excess visceral fat even without weight loss in some studies.
- And even a 5% weight loss from a combination of lifestyle strategies tends to reduce waist size and often produces a 15% to 25% drop in the visceral fat that underlies inflammation, insulin resistance, and development of metabolic syndrome.
Caveat: Some people are more genetically prone to deposit excess calories in visceral and ectopic fat that is behind the development of metabolic syndrome. So metabolic syndrome that’s reversed does not mean vanquished forever. The goal needs to be developing a lifestyle built on realistic choices can continue long-term.
Back to that Iceberg…
“I wish I’d seen that coming.” Nobody likes to face unfortunate outcomes and realize in hindsight that they might have been able to avoid or delay those circumstances with steps they could reasonably have taken.
Metabolic syndrome is one of those calls to action. Yes, you can put off paying attention to blood pressure consistently on the rise, or blood lipids or blood sugars creeping out of a healthy range. But identifying the constellation of factors that make up metabolic syndrome offers a chance to “turn the ship around.”
And that’s why it’s worth talking about.
Bottom Line on What Causes Metabolic Syndrome & Why We Need to Talk About It
Metabolic syndrome is a constellation of factors, each of which is a risk factor for chronic disease. Based on current research, we can do better than looking at each individual factor, like blood pressure, blood sugar, or triglycerides, as a single problem to deal with.
Addressing the underlying conditions of excess visceral fat, chronic inflammation, and insulin resistance makes it possible to promote multiple aspects of good health. And the good news is that achievable adjustments in lifestyle can take this from daunting to doable. In the next research review, we’ll examine the research on the specifics of what that involves.
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Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009 Oct 20;120(16):1640-5.
Carey RM, Wright JT Jr, Taler SJ, Whelton PK. Guideline-Driven Management of Hypertension: An Evidence-Based Update. Circ Res. 2021;128(7):827-846.
Eslam M, Sanyal AJ, George J; International Consensus Panel. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020 May;158(7):1999-2014.e1.
Friedman DN, Tonorezos ES, Cohen P. Diabetes and Metabolic Syndrome in Survivors of Childhood Cancer. Horm Res Paediatr. 2019;91(2):118-127.
Guerrios-Rivera L, Howard LE, Wiggins EK, et al. Metabolic syndrome is associated with aggressive prostate cancer regardless of race. Cancer Causes Control. 2023 Mar;34(3):213-221.
Jia G, Sowers JR. Hypertension in Diabetes: An Update of Basic Mechanisms and Clinical Disease. Hypertension. 2021 Nov;78(5):1197-1205.
Karra P, Winn M, Pauleck S, et al. Metabolic dysfunction and obesity-related cancer: Beyond obesity and metabolic syndrome. Obesity (Silver Spring). 2022 Jul;30(7):1323-1334.
LeBlanc S, Coulombe F, Bertrand OF, et al. Hypertriglyceridemic Waist: A Simple Marker of High-Risk Atherosclerosis Features Associated With Excess Visceral Adiposity/Ectopic Fat. J Am Heart Assoc. 2018 Apr 13;7(8):e008139.
Micucci C, Valli D, Matacchione G, Catalano A. Current perspectives between metabolic syndrome and cancer. Oncotarget. 2016 Jun 21;7(25):38959-38972.
Neeland IJ, Ross R, Després JP, et al. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement. Lancet Diabetes Endocrinol. 2019 Sep;7(9):715-725.
Okwuosa TM, Morgans A, Rhee JW, et al. Impact of Hormonal Therapies for Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart Association. Circ Genom Precis Med. 2021 Jun;14(3):e000082.
Pluta W, Dudzińska W, Lubkowska A. Metabolic Obesity in People with Normal Body Weight (MONW)-Review of Diagnostic Criteria. Int J Environ Res Public Health. 2022 Jan 6;19(2):624.
Powell-Wiley TM, Poirier P, Burke LE, et al. Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2021 May 25;143(21):e984-e1010.
Rao G, Powell-Wiley TM, Ancheta I, et al. Identification of obesity and cardiovascular risk in ethnically and racially diverse populations: a scientific statement from the American Heart Association. Circulation. 2015;132(5):457–472.
Rinella ME, Lazarus JV, Ratziu V, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023 Jun 20:S0168-8278(23)00418-X.
Schulze MB. Metabolic health in normal-weight and obese individuals. Diabetologia. 2019 Apr;62(4):558-566.
Shi TH, Wang B, Natarajan S. The Influence of Metabolic Syndrome in Predicting Mortality Risk Among US Adults: Importance of Metabolic Syndrome Even in Adults With Normal Weight. Prev Chronic Dis. 2020 May 21;17:E36.
Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association. Circulation. 2023 Feb 21;147(8):e93-e621.
Wang JS, Xia PF, Ma MN, et al. Trends in the Prevalence of Metabolically Healthy Obesity Among US Adults, 1999-2018. JAMA Netw Open. 2023 Mar 1;6(3):e232145.
Wu H, Ballantyne CM. Metabolic Inflammation and Insulin Resistance in Obesity. Circ Res. 2020 May 22;126(11):1549-1564.
Zhou XD, Targher G, Byrne CD, et al. An international multidisciplinary consensus statement on MAFLD and the risk of CVD. Hepatol Int. 2023 May 19:1–19.
Published : July 17, 2023
Tagged: adipose, cancer prevention, cancer risk, cancer survivors, CVD, heart disease, heart disease prevention, heart health, high blood pressure, hypertension, inflammation, insulin resistance, MASLD, metabolic syndrome, NAFLD, reducing cancer risk, triglycerides, visceral fat, waist circumference, waist size
Meet the author/educator
Karen Collins
MS, RDN, CDN, FAND
I Take Nutrition Science From Daunting to Doable.™
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