Metabolic Syndrome and Insulin Resistance

The metabolic syndrome is a constellation of risk factors, most usually associated with increased body weight, fat accumulation around the abdominal organs often termed central, or visceral obesity (1), and increased resistance to the effects of insulin.

Metabolic Syndrome (Insulin Resistance Syndrome)Other names that have been used to describe the metabolic syndrome are syndrome X, the insulin resistance syndrome, the deadly quartet (2) and obesity dyslipidemia syndrome (3).

The first description of metabolic syndrome can be traced to Eskil Kylin (1889-1975) (4), a Swedish physician who described a cluster of conditions, including high blood sugar, high blood pressure, obesity, and high blood levels of uric acid (5) which can lead to gout (6).

The prevalence of metabolic syndrome has grown rapidly. It is estimated that around 70 million people in the US have metabolic syndrome or about one-third of all adults in the country (7).

Data from NHANES III (8) have shown that factors associated with the risk of developing metabolic syndrome, apart from age, race and body weight, are postmenopausal status among women, smoking, low household income, high carbohydrate diet, no alcohol consumption, and physical inactivity.

The fact that the metabolic syndrome is highly related to the risk of developing type 2 diabetes and cardiovascular disease underscores the importance of understanding, preventing and treating the disorder.

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Definition of The Metabolic Syndrome

It is debated whether the factors associated with the metabolic syndrome have enough in common to warrant classifying it as a true syndrome (9).

Although the metabolic syndrome is often referred to as a uniform entity, it is important to recognize that no single underlying mechanism has been defined, nor may one exist. Thus, the syndrome could range from a cluster of unrelated risk factors to a constellation of factors linked through a common underlying mechanism (10).

For scientific and public health purposes, for example, when large numbers of people are targeted, using the term metabolic syndrome may be useful.

For the individual, it may be more practical to look at the different components of the metabolic syndrome because the clinical picture varies between patients.

The five conditions described below are used to define the metabolic syndrome. Three of these must be present in order to be diagnosed with the condition.

  • Abdominal obesity, defined as waist circumference > 40 inches (102 cm) in men and > 35 inches (88 cm) in women
  • A high triglyceride level in blood, defined as > 150 mg/dL (1.7 mmol/L)
  • A low HDL cholesterol level in blood, defined as < 40 mg/dL (1 mmol/L)
  • High blood pressure, defined as > 130/85 mmHg or drug treatment for elevated blood pressure
  • Elevated blood sugar, defined as fasting blood glucose >100 mg/dL (5.6 mol/L) or drug treatment for diabetes

The Role of Body Weight

Gaining weight is a major risk factor for the metabolic syndrome. Data from NHANES III have shown that the metabolic syndrome was present in 5 percent of normal weight individuals, 22 percent of those who were overweight and 60 percent of those who were obese (8).

Abdominal obesity appears to play a key role. A large waistline alone identifies up to 46 percent of individuals who will develop metabolic syndrome within five years (11).

The rapidly increasing prevalence of obesity in most countries around the world (12) is likely to raise the prevalence of the metabolic syndrome further in the near future.

The Role of Insulin Resistance

Insulin resistance plays a key role in the pathophysiology of the metabolic syndrome and the term “insulin resistance syndrome” has been used by some experts (13).

Insulin is a peptide hormone produced by beta cells in the pancreas (14). It plays an important role in the metabolism of carbohydrates and fats.

When sugar and carbohydrates are ingested, insulin promotes the uptake of glucose (sugar) from the blood into the cells of skeletal muscle and fat tissue. Hence, it is often said that insulin unlocks the cell to allow sugar to enter and be used for energy. Insulin also promotes the storage of energy in the form of glycogen and fat.

When blood glucose levels fall, stored glucose is released for energy utilization from the breakdown of glycogen stores in the liver and skeletal muscle.

If the pancreas is unable to produce enough insulin in response to meals or if the action of insulin is impaired, glucose will accumulate in the blood and blood sugar will become high as is the case in diabetes.

The ability of insulin to stimulate glucose disposal varies more than six-fold in apparently healthy individuals (15). Between 25-35% of the variability in insulin action is related to being overweight. In other words, when body weight increases, insulin resistance becomes more likely.

Insulin resistance is defined as a diminished response to a given concentration of insulin. Initially, the pancreas responds by producing more insulin. For this reason, individuals with insulin resistance often have high levels of insulin in their blood. However, as diabetes develops, the beta cells of the pancreas often become unable to produce more insulin and its blood levels drop.

Individuals with insulin resistance are at greatly increased risk to develop heart disease, type 2 diabetes, high blood pressure, stroke, nonalcoholic fatty liver disease (16), polycystic ovary syndrome (17), and certain forms of cancer.

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How to Identify Insulin Resistance

Insulin resistance appears to be associated with increased risk of type 2 diabetes, heart disease, and certain cancers associated with obesity. For this reason, it would be useful to identify obese individuals who are insulin resistant. However, there is currently no validated test for measuring insulin resistance in a clinical setting.

Blood levels of triglycerides, the ratio of triglyceride to HDL cholesterol concentrations (18), and fasting insulin concentration may be useful markers for identifying those who may be insulin resistant. A study in which most of the participants were Caucasian and overweight identified triglyceride/HDL cholesterol ratio of 3 or greater as a reliable predictor of insulin resistance (19).

The most widely used test is the homeostasis model assessment of insulin resistance (HOMA-IR), which employs fasting glucose and insulin levels (20). Due to biological variability requiring repeat testing and lack of insulin assay standardization, HOMA-IR continues to be used more for research than for clinical applications.

Recently, a so-called Lipoprotein Insulin Resistance Index (LP-IR), based on blood measurements of lipoprotein subclasses and particle concentration, has been used to measure insulin resistance (21). This test is being performed in some laboratories in the US.

Metabolic Syndrome and Insulin Resistance

Metabolic Syndrome – Why We Should Care

The metabolic syndrome is an important risk factor for the development of type 2 diabetes and cardiovascular disease.

A meta-analysis of 16 prospective observational studies showed that the metabolic syndrome is a significant predictor of incident diabetes in many different populations, including Native Americans, U.S. Hispanics, Mexicans, Turks, Iranians, Mauritians, Chinese, Europeans, and those of European descent(22).

A 2005 meta-analysis (23) found that the presence of the metabolic syndrome was associated with a 12-17 percent increased risk of cardiovascular mortality, and 6-7 percent increased risk of overall mortality.

The increased risk of diabetes and cardiovascular disease appears to be related to the presence of risk factor clustering and insulin resistance associated with the metabolic syndrome, rather than obesity by itself (24).

The metabolic syndrome is associated with elevated levels of inflammatory markers (25). Chronic low-grade inflammation is associated with increased risk of type 2 diabetes and heart disease (26).

In the presence of obesity, adipose tissue produces inflammatory cytokines, whereas adiponectin (27) production is diminished (24). Inflammatory cytokines induce insulin resistance in both adipose tissue and muscle (28).

Hence, inflammation might be an important pathogenic link between cardiovascular diseases, insulin resistance, and metabolic syndrome.

Other disorders associated with the metabolic syndrome are non-alcoholic fatty liver disease, chronic kidney disease, polycystic ovary syndrome, obstructive sleep apnea and gout.

Treatment of Metabolic Syndrome

There are two major treatment targets in patients with the metabolic syndrome. The first aims at treating underlying causes such as obesity and physical inactivity. The second aims at treating cardiovascular risk factors if they persist despite lifestyle modification.

Lifestyle modification should focus primarily on weight reduction and increased physical activity (29).

Diet

Any diet that promotes weight reduction and reduces insulin resistance is likely to be beneficial for people with metabolic syndrome.

A Mediterranean diet is characterized by high consumption of monounsaturated fatty acids, primarily from olives and olive oil. It encourages daily consumption of fruits, vegetables, whole grains, and low-fat dairy products; weekly consumption of fish, poultry, tree nuts, and legumes; a relatively low consumption of red meat, as well as a moderate daily consumption of alcohol, normally with meals.

A meta-analysis of epidemiological studies and clinical trials published 2011 shows that adherence to the Mediterranean dietary pattern was associated with lower prevalence and progression of metabolic syndrome (30). Waist circumference, HDL cholesterol levels, triglyceride levels, blood pressure levels, and glucose metabolism were all positively affected.

In a study comparing a Mediterranean diet with a prudent low-fat, high carbohydrate diet, individuals on the Mediterranean diet had greater weight loss, lower blood pressure, less insulin resistance and better lipid profile (31). Markers of inflammation were also lower compared with the prudent diet.

Metabolic Syndrome (Insulin resistance Syndrome)Several studies suggest that carbohydrate restriction has more favorable effects on the metabolic syndrome than a low-fat diet (32, 33, 34, 35, 36). Low-carbohydrate diets tend to lead to more weight loss, less insulin resistance, lower triglyceride levels, and higher levels of HDL-cholesterol.

A 2012 meta-analysis of randomized trials of low-carbohydrate diets for weight loss showed positive effects on body weight, body mass index (BMI), abdominal circumference, blood pressure, blood sugar, plasma triglycerides and HDL cholesterol (37).

Exercise

Regular exercise is highly recommended for individuals with metabolic syndrome.

Exercise may be beneficial, beyond its effects on weight loss. One study suggests exercise may reduce abdominal fat among women (38).

A standard exercise recommendation is a daily minimum of 30 minutes moderate exercise such as brisk walking.

Increasing the level of physical activity may provide further benefits.

Treating Cardiovascular Risk Factors

Cessation of smoking and treatment of high blood pressure, lipid abnormalities, and diabetes is important for patients with metabolic syndrome.

Statins (cholesterol-lowering drugs) are usually recommended if diabetes is present or if levels of LDL cholesterol are high (39).

Metformin (40) is usually the first drug of choice if type 2 diabetes becomes manifest.

The Take Home Message

The prevalence of metabolic syndrome has increased rapidly in recent years.

Metabolic syndrome is usually associated with overweight, abdominal obesity and insulin resistance.

The metabolic syndrome is highly related to the risk of developing type 2 diabetes and cardiovascular disease

Treatment aims at weight reduction and increased physical exercise.

Scientific evidence suggests the Mediterranean diet and low-carbohydrate diets are more effective than other diets for treating metabolic syndrome.

Cessation of smoking and treatment of hypertension, lipid abnormalities, and diabetes is important.

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63 thoughts on “Metabolic Syndrome and Insulin Resistance”

  1. “A 2012 meta-analysis of randomized trials of low carbohydrate diets for weight loss showed positive effects on body weight, body mass index (BMI), abdominal circumference, blood pressure, blood sugar, plasma triglycerides and HDL cholesterol.”

    The full study
    https://www.swissmilk.ch/fileadmin/filemount/santos-12-systematic-review-and-meta-analysis-of-clinical-trials-of-the-effects-of-low-carbohydrate-diets-on-cardiovascular-risk-factors.pdf

    From the study “LCD was shown to have favorable effects on body weight and major cardiovascular risk factors; however THE EFFECTS ON LONG-TERM HEALTH ARE UNKNOWN”

    “The long-term effects of LCD, as well as the effects of LCD on clinical endpoints such as the incidence of myocardial infarction, stroke and total mortality, are UNKNOWN, and concern has been raised on the ‘reliance on the traditional cardiovascular risk factors as a gauge of safety'”

    “the long-term effects of LCD, as well as the effects of LCD on clinical endpoints such as the incidence of myocardial infarction, stroke and total mortality, are essentially UNKNOWN and should be the object of future research.”

    • bu the government says we should eat lots of carby bullshit and avoid fat! why would they lie! let me guess! their bullshit “studies” of the 50s have become conventional wisdom and theyve gone too far to say “ya know we kinda got that wrong”…too late fuckers the wisdom of crowds has fought back making you guys look like idiots

  2. I find it hard to go on low carb diets because I exercise quite a bit and am always hungry afterwards.

    So I try to stick to eating as few refined carbs as possible, limit SFA, eat healthy fats (avocado, chia, some fish), struggle to limit sugar as I have a crazy sweet tooth.

    All of this stuff makes loads of sense and I’d be really surprised if people dodn’t know this stuff.

    The hard part is doing it and sticking to it.

    Keep up the good work Doc.

    Any chance you could do a request piece on diets for those of varying apoe status or diets to reduce LDL-P?

    regards

    • LDL number doesn’t matter as much as LDL particle size. Also regardless of ApoE status, the best way to reduce small dense LDL particles (which have a tendency to oxidize, persist in circulation for weeks and contribute to atherogenesis) and convert them to large buoyant LDL particles (which do not persist in circulation) whilst simultaneously increasing HDL particles is low carbohydrate high fat diet and in particular increasing intake of saturated fat.

      • Dr Dayspring (aka Dr Lipid – use Google) would disagree about LDL-P vs LDL size. He claims large particle can “crash” into the artery wall just as well as small ones. I don’t know who to believe.

        I did see a chart done by a “civilian” on a forum somewhere that showed particle number and size pretty much tracked each other up until LDL-P got to the mid 1000’s (i.e. around 1500) then decreased size really increased risk. I wish I could find it again.

  3. Excellent article. I developed this syndrome in my late 30’s and it got progressively worse in my 40’s. I had high triglycerides, low HDL, fatty liver, high blood pressure, and kept getting fatter and more miserable. I did develop type 2 diabetes. I discovered low carb diets and started eating that way in 1999. I now have normal body weight, hbg a1c is 5.2, I lift weights and do cardio 5 days a week and have never felt better in my life. Eating a low carb diet and doing regular exercise has saved my life. I eat very high fat and very low carb and have for about 16 years now. It works. At least it has for me and other people I have known.

  4. I had to look up what a “prudent low carb diet” was. As one might guess, a “prudent low carb diet” is one that is low in fat. No surprise that such a diet did not fare as well as “the Mediterranean diet” (really, there’s just one?) described as high in “consumption of monounsaturated fats”. High natural fat vs starvation (remove fat from a low carb diet and not much is left)–no surprise that the so-called “prudent low carb diet” did not fare as well.

    I choose the “imprudent low carb diet”–low in carb and high in natural fats including saturated fats (which many real Mediterranean people eat along with their olive oil). This has virtually eliminated all my markers of metabolic syndrome for several years now. I’m happy to be the long-term guinea pig because this is a much better way to live my life than sick and fat on the standard medically advised low fat high grain diet.

    So far the “long term effects” have been nothing but improved health and lowered risk factors.

    • What is ”natural” fats anyway? Are you implying that the fat consumed in the med diet are unnatural? What would that mean?

      Starvation? You know that a ketogenic diet mimics starvation, right? How is a high-carb diet comparable to starvation?

      So, you are telling us that you were eating before a plant-based diet, based on fruits, vegetables, legumes and whole grain, ie, getting around 60-100g of fibers a day? Not the typical sad diet, right? And that going LC did much better than a plant-based, whole food approach?

      You mean that you are happy to keep on eating the food that you know you should no longer be eating right? A diet that tells you to gorge on meat and fatty food sure is fun to follow.

      • It seems obvious to me that “natural fats” means fats that are found in foods and exclude would trans-fats and vegetable/seed oils. And no, that wouldn’t preclude fats found in any of the multiple versions of a “Mediterranean” diets.

        The rest of your post seems to be a lot of strawmen – all Imprudent said is that a low carb, high fat diet has improved his health. He didn’t say he “gorged” on meat and fat, he didn’t say anything about his prior diet and he definitely said nothing about a high carb diet being comparable to starvation (his contention was that a low carb, low fat diet was a starvation diet ).

        It seems you’re a big fan of a plant-based diet and if that’s working for you then that’s terrific, keep doing it. But a lot of people (including myself) are having extraordinary success on a low carb, high fat diet by anything you want to measure it by. I’ve had a reversal of my asthma, I lost 35 lbs effortlessly, my hayfever has lessened significantly and I no longer have hand tremors. And that was after trying to follow a low fat diet full of whole grains. That approach simply did not work for me.

        I think the human body is amazing – it can operate and operate well on sub-optimal fuel for a long, long time before problems begin to show up. That’s probably unfortunate because it gives people the false impression that their typical diet is good for them and that any health issues that arise are just the luck of the draw. If we had acute responses to poor food choices it would be easy to see what’s good and what’s bad but unfortunately that’s not the case. So instead we get to flounder around for decades not knowing for sure if we’re doing the right thing. It’s a bummer.

    • Hi Imprudent

      It appears you’ve misunderstood the dietary discussion in the article above. In fact it’s “prudent low fat-diet” (not low-carb). So it’s not about removing fat from a a low carb diet. Nobody suggested that.

      The “prudent diet” is what’s usually recommended by public health authorities and professional societies like the American Heart Association. It’s low in fat, but relatively high in carbs.

  5. Seems that researchers might at the C-Reactive Protein blood test the test battery for metabolic syndrome. It would be good to know if inflammation is present in those with this problem.

    For my husband who had this for years, his CRP dropped from 8 mg/L to 0.5 mg/L after 10 months on a ketogenic diet.
    He is back to the weight he was when we married, 47 years ago!

    • You’re right. hs-CRP is one of the inflammatory markers that often becomes elevated in metabolic syndrome. It is easily measured in blood. The test is available at most laboratories today.

      High levels of hs-CRP are strongly related to cardiovascular risk.

      • Thanks for that.
        Back in the early 1980’s when I began working at a hospital which cared mostly for CV patents, one of our interventional cardiologists ordered a CRP on each of his patients. I had asked why because I don’t think this idea was well known back then. I was told it was just something the doctor believed was related to CVD. Perhaps he was ahead of his time.

  6. Seems that Richard Feinman might have some advice. This is from his book, The World Turned Upside Down, and he is talking about what he tells people who ask him about the ideal diet.

    “Rule 1. If you’re OK, you’re OK.

    Rule 2. If you want to lose weight: Don’t eat. If you have to eat, don’t eat carbs. If you have to eat carbs, eat low-glycemic index carbs.

    Rule 3. If you have diabetes or metabolic syndrome, carbohydrate restriction is the “default” approach, that is, the one to try first.”

    I am currently following Rule 3 and the results are worth it. I’ll see what my doctor thinks when I get my blood tested in April.

    • As always, simplistic rules are potentially misleading.

      1) Define “ok”. Subjective feeling? The first manifestation of CVD can be deadly – and just prior to that you may have been feeling a-okay.

      2. If you want to lose weight and KEEP it away, you have to eat. Low carb diets aren’t superior to any other sensible options.

      3) There’s no evidence to indicate that apart from short-term studies conducted in weight loss context.

      However, a sensible low carb diet can be pretty much as good an option as any other sensible options. So if it works for you, all the better.

      • I would like to comment the above, by adding that if you choose to low-carb, make sure to steer away from saturated fat. All of the studies documenting (the very modest, if none at all) benefit with low-carb approach on biomarkers have included a policy to guide their low-carb arm to avoid animal fats. In other words, the kind of low-carb diet used in scientific studies is very different to that which is sold in popular diet books.

      • 1) OK obviously means that your doctor qualifies you as low risk based on history of tests such as lipoprotein profile, blood pressure, inflammation markers, etc. In that case there is no need for intervention, dietary or other.
        2) What about that guy who ate nothing for 382 days in that famous case report? You don’t HAVE to eat, but it is inconvenient. There is a way to mimic the biochemical effects of total calorie restriction and it works just as fine. Especially when combined with intermittent fasting to break insulin resistance. Science disproves your statements, low carb diets are superior in general for weight loss as well as for improving other common health markers.
        3) Check out this article including references and the contributor list: https://www.sciencedirect.com/science/article/pii/S0899900714003323

  7. I am 68, and have been interested in nutrition and exercise since I was 13, having read advertisements from Joe Weider, Charles Atlas, and Jack LaLane. But, I really focused on nutrition 18 months ago when I decided to look into veganism. Now, I am convinced that discussion about nutrition is more subjective than objective because of the conflicting information available to us.

    Each of us has different inputs, and we sort through our inputs to decide which to believe – like a religion.

    There are numerous studies that show a Low Carb Diet sheds the pounds. But we are left with the long term side effects unless we take care to address them – like needing more water to compensate for low carbs, or needing more vegetables to avoid constipation.

    The more I looked into nutrition, the more I found it to be complex, and indeed it is a faith based issue because of its complexity. Results from studies and recommendations from doctors are conflicting. For example, the China–Cornell–Oxford Project shows that, in general, genes are not a determinate factor for obesity, cancer, diabetes, heart disease, or other ailments – but rather the diet is.

    The T. Colin Campbell’s book, “The China Study,” has dietary recommendations based on the Project, but there is plenty of controversy over his recommendations.

    So, one is left to decide what is best for themselves. What sources does one wish to believe in?

    Doctors? I went to a new doctor for a physical last week (new because I decided my previous doctor was fat and I don’t wish to get treated by fat doctors – it seems hypocritical to be treated for health by an unhealthy doctor). He called me after my physical and in a concerned tone said my pacemaker doesn’t appear to be working. I asked why he thought that. He said because my pulse is 47. When I told him I asked my cardiologist to set the minimal pace to 45, he said he never heard of such a thing. I tried to explain that I eat healthy and work out, and that the normal pulse for those types of people my age is 40 to 60. But he still couldn’t understand it.
    Most doctors are not a source to rely on for the final word on good nutrition – their education typically consists of very little on nutrition. My current doctor said to eat a healthy diet and exercise. But his definition of healthy is vague and controversial regardless of what guidelines he uses.
    So there you have it. The studies, doctors, and personal experience are inputs we use to decide the best diets to follow. There will never be a single best diet(or religion) that everyone can agree on.

    Each of us make our own decisions – I made mine 18 months ago – a vegan with no oil, salt, sugar, or processed foods (following Bill Clinton’s nutrition doctor Caldwell Esselstyn’s advice). Sort of like Jack LaLane, who was a semi-vegan, no oil, salt, sugar or processed foods. He worked out every day until the day before he died at 96.

    But, one point is certain – people who ignore nutritional information and eat junk, will be leaving the gene pool early.

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