Diabesity and Inflammation: A Case of Chicken and Egg
In a previous article, I introduced the term “diabesity”, the description of Type 2 diabetes when it occurs in the context of obesity. Insulin resistance is defined by an inability of the body to respond to insulin and use up glucose in the blood. When insulin resistance sets in and glucose builds up in the blood, pancreatic beta cells produce excess insulin in an effort to bring down that glucose level. Diabesity is triggered by the onset of insulin resistance.
Because diabesity is diabetes in the context of obesity, we have to recognize that inflammation caused by obesity also plays a role in the onset of diabetes. Here, we will discuss what role inflammation plays and why it might be the most important mechanism fueling the diabesity epidemic.
Why are anti-inflammatory drugs not the mainstay of diabetes type 2 treatment?
Before delving into the connection of the diabesity-inflammation pendulum, I decided to throw in a teaser. This quote is taken 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. It is believed that sodium salicylate was dropped because of the serious side effects it causes when given in high doses.
Let’s move on to the pendulous relationship between diabesity and inflammation.
How does Inflammation Cause Diabesity?
There are several lines of evidence linking inflammation with obesity and diabetes; here are 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.
2. Inflammation causes insulin resistance
Inflammation of the fat tissue causes insulin resistance, the primary cause of diabesity. A small protein known as TNF-α which is released during inflammation has been shown to cause insulin resistance, and other inflammatory proteins such as MCP-1 and C-Reactive protein have also been linked to insulin resistance.
3. 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 a hormone produced in fat cells that sends signals to the hypothalamus in order to regulate hunger and energy. It is sometimes called the starvation hormone and sometimes the obesity hormone. Leptin resistance happens when your body is no longer responsive to leptin, causing your brain to be fooled into believing that you are starving 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 builds up in anabolic processes while inflammation breaks down in catabolic processes. 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.
2. 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, setting up a proportional connection between the amount of fat tissue you have and the amount of inflammation your body experiences.
The Chicken Versus the Egg
It is clear that there is a direct relationship between diabesity and inflammation, but it is very difficult to determine which comes first. Inflammation is both a major cause of diabesity and occurs as a result of 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 believe the best approach towards the treatment or prevention of diabesity has to begin with addressing the underlying inflammation, and it should also involve treating inflammation once diabesity has occurred. Current modern clinical approach is focused on regulating blood sugar without addressing inflammation. Unfortunately, such an approach is bound to produce inferior results.
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