I have mentioned the term metabolic syndrome (MetS) several times in response to the content of the lectures of Dr Lustig but I have never discussed its definition here. Instead of copying straight the most recent definition from 2009 which I used for my dissertation, I continue in my habit and focus on what Dr Lustig said. I will eventually come to the 2009 content later on.
You could hear from the minute 8:45 of the lecture onwards about the disagreement of six different metabolic MetS and what variables should be assessed in order to classify someone as suffering the condition.
Dr Lustig dismissed the classic diagnostic criteria for MetS as phenomenological (via the cut-offs of various factors such as waist circumference, blood pressure, etc) and suggested that the mechanistical approach should be used instead:
He further pointed at two aspects of this mechanistical approach:
- where is the subcellular dysfunction
- where is the insulin resistance.
This was presented as a widely agreed and accepted mechanism of manifestation of MetS. I have no problem with that, but I also do not see a big problem with the previous system. It is a syndrome and its features appear in different combinations and severity in different people. Disease has a specifically defined points which also have to be met for a person to be classified as suffering that particular disease. And, from my point of view, the MetS is an equivalent of a disease once present in an individual.
Going back to the second picture and looking at the final question: Where is the insulin resistance? makes me puzzled. Insulin resistance syndrome or Syndrome X were older names for what we call the metabolic syndrome today and some sources are still using the first one.
Dr Lustig mentioned six different definitions by six different health bodies in the first image. One of these was the IDF 2005 which stands for International Diabetes Federation. Where is the insulin resistance? Well, If you look at their Table 3 you will find it there. It is one of the additional criteria of metabolic syndrome for research. These criteria are more biochemical than physiological, which are used in the clinical definition of MetS and are present in various combinations among those six definitions discussed earlier. IDF also reported on the definition of MetS in children and adolescents.
For now we have the most recent definition of metabolic syndrome for adults, published in 2009 in the Circulation journal, titled Joint Scientific Statement by Alberti et al. Why this definition did not appear among those six presented in this video of Dr Lustig uploaded in 2014, I do not know.
Overall, the usual five main symptoms of MetS (not including the test for insulin resistance itself) are called the clinical criteria, the additional ones are used for research and these do include insulin resistance assessment, which is more complicated than simply measuring fasting glucose concentration in blood. But in the past these main clinical criteria were known as 'insulin resistance syndrome'. Today, when in doubt, the insulin resistance can also be assessed on demand by the laboratories.
Now I would like to ask a question: does the person have to be insulin resistant in its own definition to be diagnosed clinically as having a metabolic syndrome? Cannot there just be a hypertension, dyslipidemia (which covers triglycerides and HDL) and increased waist circumference? I recall hearing Dr Lustig saying in another video that when a person develops insulin resistance, it is already very bad. So? Does he want people to be diagnosed with metabolic syndrome only when they become very sick or would it be better for them and the society if they were diagnosed a bit earlier when not all of them have come to this more serious condition? People, for being suspected for having insulin resistance, do not necessarily have to have elevated blood glucose for being announced metabolically abnormal and therefore heading towards cardiovascular disease or diabetes.
So Dr Lustig called for the insulin resistance as the mechanistic approach instead of those cut-off points he criticized. WHY? Even for the insulin resistance, there are some numerical criteria serving the purpose of cut-off points used to assess whether the person does suffer from insulin resistance or not. There is no other way to assess this condition than to set up certain threshold which will distinguish two individuals as one having this feature and other not having it.
At 10:09 minute Dr Lustig continues with the explanation of what he means by the mechanistic approach:
- where is the cellular dysfunction
- where is the insulin resistance.
Well, according to the Wikipedia summary of methodologies for the measurement of the insulin resistance, it truly appears as a mechanistic approach. The do not make one-off assessment of the blood biochemistry and make a conclusion. The test is more intrusive and restrictive on the tested person and now I hope you understand why this MetS criterion was rather included into the research than for the clinical assessment of a usual patient visiting the GP for regular health check.
I have no objections against the assessment of the insulin resistance, but would that be necessary for the MetS diagnosis, practicable on a large scale (as an alternative to a simple fasting blood glucose test) and affordable for the healthcare system? I do not think so.
And still, this does not give an answer to the questions mentioned above: WHERE is the cellular dysfunction and WHERE is the insulin resistance? This is even more complicated problem and I have looked at it in another article of this blog.
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