Diabesity and Inflammation: A Case Of Chicken And Egg?

November 19, 2019

In our previous article, I introduced the term diabesity. In case you haven’t read it, you can check it here (link to what is diabesity). In a nutshell, diabesity is the description of diabetes type 2 when it occurs in the context of obesity. Diabesity is triggered by the onset of insulin resistance which means that insulin is not able to take out glucose from the bloodstream. Insulin resistance is often accompanied by excessive insulin as the beta cells of the pancreas keep producing more insulin to get rid of excess sugar. In this article, we will discuss what role inflammation plays and why it might be the most important mechanism fuelling the diabesity epidemic.

Why are anti-inflammatory drugs not the mainstay of diabetes type 2 treatment?

Before delving into the meat of the diabesity-inflammation pendulum, I decided to throw in a teaser.  I will quote from an article published in JCI in 2006 titled “Inflammation and Insulin Resistance.”

“Clues to the involvement of inflammation in diabetes date back to more than a century ago when high doses of sodium salicylate (5.0–7.5 g/d) were first demonstrated to diminish glycosuria in diabetic patients having type 2 diabetes. In 1876 Ebstein concluded that sodium salicylate could make the symptoms of diabetes mellitus totally disappear.”

Why then are anti-inflammatory agents not the mainstay of diabetes type 2 treatment? This is indeed a controversial topic. However, it is believed that sodium salicylate was dropped because of the serious side effects it causes when given in high doses.

Now we can look at the pendulous relationship between diabesity and inflammation.

How does Inflammation Cause Diabesity?

There are several lines of evidence linking inflammation with obesity and diabetes. I will outline a few:

  1. Inflammatory markers are elevated prior to the diabesity.

Elevated levels of inflammatory cytokines could indicate future weight gain and obesity. A lab study also showed that an infusion of inflammatory cytokines into healthy mice causes insulin resistance.

This idea is also supported by the fact that people with other chronic inflammatory conditions are more likely to develop diabesity and type 2 diabetes.

  1. Inflammation causes insulin resistance

Inflammation of the fat tissue causes insulin resistance, which is the primary cause of diabesity. A small protein known as TNF-α which is released during inflammation has been shown to cause insulin resistance. Other inflammatory proteins such as MCP-1 and C-Reactive protein, have also been linked to insulin resistance.

  1. Inflammation in the brain causes leptin resistance

Inflammatory signaling in the hypothalamus has been linked to leptin resistance in both animals and humans. Leptin is produced in fat cells but exerts its effects primarily in the hypothalamus. It is the starvation hormone, but it is also referred to as the obesity hormone. Leptin resistance means that your body is no longer responsive to the hormone leptin. When this happens, your brain is fooled into believing that you are starving and hence you need to keep eating more and more food. Eventually, this leads to diabesity.

How Does Diabesity Cause Inflammation?

For a long time, it was believed that fat is an inert tissue with no biological activity. However, it is now known that fat is a metabolically active endocrine organ that produces hormones and inflammatory molecules. The feature of fat is the key to understanding its role in diabesity and inflammation.

  1. Diabesity induces inflammation as a protective mechanism.

Diabesity causes the buildup of fat around the waist. Fat storage is an anabolic process while inflammation is a catabolic process. The body may activate catabolism through inflammation so as to keep weight within acceptable limits. Experimentally induced inflammation in fat tissue has been shown to initiate weight loss and improve insulin resistance.

  1. Diabesity related stresses could cause inflammation

Obesity has been associated with chronic low-level inflammation. it is hypothesized that the stresses of diabesity are similar to the stresses caused by an infection. As a result, the body responds in a similar way by triggering inflammation.

Obesity has also been linked to the release of inflammatory compounds such as TNF-α. This means that the more fat tissue you have, the more inflammation you are likely to have.

The Chicken Versus The Egg

It is clear that there is a direct relationship between diabesity and inflammation. However, it is not very clear which factor precedes the other. Inflammation is both the cause and the result of diabesity. Inflammation plays a big role in causing diabesity. On the other hand, the occurrence of diabesity can further stimulate the production of inflammatory cytokines, forming a vicious cycle of inflammation and diabesity.

We can then confidently conclude that the best approach towards the treatment or prevention of diabesity has to begin with addressing the underlying inflammation. It should also involve treating inflammation once diabesity has occurred. The modern clinical approach is focused on regulating blood sugar without addressing inflammation.  Unfortunately, such an approach is bound to produce inferior results.

  • References

1.   ADA: Inflammation-Sensitive Plasma Proteins Are Associated With Future Weight Gain.  Retrieved from https://diabetes.diabetesjournals.org/content/52/8/2097.full?ijkey=c30ecf67b38ac20bc59ecf06ac0a8cbb539532fc

2.   NCBI (1993): Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/7678183?dopt=Abstract

3.   NCBI (2012): Obesity is associated with hypothalamic injury in rodents and humans. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248304/

4.   JCI (2005): Inflammation, stress, and diabetes. Retrieved from https://www.jci.org/articles/view/25102/version/1

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