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Modeling Modern Disease – Part 2

Previously I established that, contrary to modern clinical practice, chronic, noncommunicable diseases are not really separate and distinct illnesses, but are instead specific manifestations arising from variations in the same underlying causes*. Although current clinical practice is to diagnose and treat modern disease as separate, distinct illnesses, the reality is that each disease is most often just one severe manifestation of the overall malfunctioning of particular systems that make up the body.

There are a number of well-established mechanisms driving the progression of each modern disease. These mechanisms include, but are not limited to: inflammation, oxidative stress, excess fat accumulation, hyperglycemia, and dyslipidemia.

Any one disease can arise driven by any number of underlying mechanisms, creating a dysfunctional sub-system. For example, cardiovascular disease (CVD) may arise due to a combination of systemic inflammation, dyslipidemia, oxidative stress, and hyperglycemia. The disease manifests as a diagnosable illness when these mechanisms drive the dysfunction of a particular sub-system. In the case of CVD, these underlying mechanisms cause damage to and disrupt the functioning of the arteries, causing atherosclerosis and CVD.

Image 1: Cardiovascular disease (CVD) is driven, to a great extent, by three underlying mechanisms. These same underlying mechanisms may also drive other disease-states in slightly varied contexts

Moving forward, when we consider modern disease in its entirety, the model gets more complicated as we must factor in multiple diseases. It’s tricky enough that multiple underlying mechanisms interact to create any one disease. It gets even trickier when you consider that the interplay between each of these underlying mechanisms drives forward any number of diseases.

Three underlying mechanisms combine to drive modern disease

Of course, looking at the system with this model greatly misses the true picture. These mechanisms do not combine in a linear manner to create a disease. Rather, they combine as a non-linear, dynamic system, from which disorder progresses, eventually leading to a disease diagnosis. In reality, these underlying mechanisms feed off each other, progressing as a system until their severity becomes clinically relevant, thus creating a diagnosable disease.

Moreover, thinking of these underlying mechanisms as simple and linear, themselves, is an additional oversimplification. Each of these underlying mechanisms (i.e. inflammation, oxidative stress, excess fat circulation) are themselves emergent properties of sub-systems. For example, inflammation progresses as sub-mechanisms progress, thus creating an inflammatory state which gradually builds up due to the other sub-mechanisms.

Thus, a better model is one that reflects each underlying mechanism as its own sub-system, and additionally reflects that each of these underlying mechanisms is in constant feedback with each other underlying mechanism:

At this point, let’s give the dysfunction of these underlying mechanisms a name, as it is a well-established state. The condition defined by the numerous disrupted mechanisms which drive modern disease is commonly called metabolic syndrome. Metabolic syndrome is defined by having a number of symptoms (usually 3, 4, or more) related to the underlying mechanisms discussed herein (e.g inflammation, hyperglycemia, dyslipidemia, excess fat accumulation, etc). For now, we will avoid getting into metabolic syndrome as it is clinically described, as at this point, for our purposes, all we need to know is it is a state that exists, it is a core driver of modern disease, and that it is defined by the disruption in these underlying mechanisms.

This makes for the following upgraded model:

Using this model we can clearly see that modern disease is not the linear progression of a select few underlying mechanisms. Rather, a number of underlying mechanisms, themselves arising from subsystems, combine in a dynamic, non-linear fashion to create modern disease.

Let’s take a moment to reflect on this model.

Let us make sure we have established the basis of our model thus far.

  • Any number of underlying mechanisms combine in a non-linear, dynamic fashion from which the progression of modern disease is driven
    • specific disease diagnoses arise when these underlying mechanisms manifest in clinically relevant symptoms in particular systems in the body (e.g. CVD arises when a combination of inflammation, hyperglycemia, dyslipidemia, etc. cause significant
      disorder in the cardiovascular system, resulting in clinical symptoms, such as a blood clot and heart attack)
  • This system is significantly influenced by feedforward mechanisms, with one mechanism driving the progression of others, in turn driving the progression of others
  • Each mechanism is itself, a sub-system.
    • For example, inflammation, which drives the progression of disease (e.g. inflammation plays a role in the development of an atherosclerotic plaque) is itself created from underlying mechanisms (e.g. locally via oxidized lipoproteins or stress, or globally due to obesity)
  • These underlying mechanisms, when present in any one body, are termed metabolic syndrome.

A note here – if you find yourself confused by some of the technical aspects of what we just covered, there’s no need to worry. The purpose of building this model is not to get you to fully comprehend the inner workings of the model; rather, it is to help you understand why modern disease is modeled in such a way as I have it here. As long as you understand the inadequacies that go along with modeling modern disease as a simple, linear progression of a few underlying mechanisms, and as long as you understand that there is a need to model modern disease as a complex, dynamic system, then we can move forward.

How do we effectively address metabolic syndrome?

Now, that we have a model of the underlying mechanisms driving the progression of modern disease, we can move on to explaining and addressing this condition. Let’s move forward now with the question of how we will be able to address this condition.

When it comes to choosing a particular underlying mechanism to target, we have a number of options to choose from. If all of these mechanisms are at play driving a disease-state forward, then which mechanism are we to choose to target with a therapy?

Answering this question is tricky – if our goal is to prevent or reverse each of these diseases, but each of these diseases arises from a complex interplay between all these other sub-systems, then where are we to begin?

Should we tackle what seems to be the most relevant mechanism for a particular disease, as is the common approach today? For example, as is the case in CVD, we could target LDL cholesterol, which is one sub-component of one sub-system. Could targeting this one specific mechanism help us fix the
entire system?

Or, as is the case with TIID, we could target the hypoglycemia, as this is the most threatening underlying component.

Unfortunately, as we know all-too-well, this approach does not work well to effectively address disease. We can’t pick apart a system as complex as the human body and hope that by fixing one component that the whole problem will be fixed. That is simply not the nature of non-linear systems.

So then, what are we to do?

If you’ve been following along, then you probably have the answer. We have on our hands a non-linear, dynamic system, and we need to create an approach that addresses this system as such. Therefore, instead of picking apart the system to address particular components, we need an approach that will address the system as a whole – an approach that will target the entire functioning of the system all at once, thus working to fix each and every dysfunctional mechanism.

A. The traditional approach to treating disease is to pick a particular dysregulated mechanisms and address that one sub-component. Unfortunately, this approach often fails as it does not account for the nature of the system as a tightly intertwined, dynamic network. B. By targeting the system as a whole, we can address each mechanism and its relationship to each and every other mechanism.

This second approach seems logical, because if we can address each and every disrupted mechanism with one broad approach, then we need not worry about all the tiny intricacies in each dysfunctional piece of the system. However, this approach does present itself with its own set of problems. Thinking along the lines of addressing the entire system all at once sounds like a fine and dandy plan, but how is this actually done? How can we employ such a broad scope when we have a large number of specific mechanisms at play?

Does such an approach exist in practice?

Naturally, it does. Fortunately, this system lends itself to a rather simple solution, creating an answer that nicely balances the two sides. On the one hand, we need to keep our approach broad enough so that we tackle disease as a whole (Approach B). On the other hand, we need to make sure that our approach is effectively addressing the underlying pathophysiology. Instead of focusing all our attention on any one particular dysfunctional sub-system, like has been done in traditional medicine (Approach A), our approach must target each and every sub-system all at once. This means that we need to choose a broad approach that, by its inherent nature, fixes the entire system by correcting all of the disrupted underlying mechanisms.

Finding such a solution may sound challenging, but fortunately, the nature of the modern disease problem has a quite simple solution. If you think about it, this metabolic dysfunction has to arise from somewhere. There must be some physical force, somewhere, driving this dysfunction. If we can determine what that driving force is, then maybe we can target it, thus targeting modern disease as a whole.

Up next, we’ll work to answer this question.

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