The answer is both. Inflammation drives diabesity, which is type 2 diabetes in the setting of obesity. It does this by causing insulin resistance and leptin resistance. Diabesity in turn pumps out more inflammatory cytokines (signaling proteins that drive inflammation). That makes a vicious cycle. That is why treatment has to address the inflammation, not just regulate blood sugar.
In our last article, I introduced the term diabesity. If you haven’t read it, you can check it out here. In short, diabesity is type 2 diabetes when it shows up together with obesity. Diabesity is set off by insulin resistance. That means insulin can no longer pull glucose out of the bloodstream. Insulin resistance often comes with too much insulin. That is because the beta cells of the pancreas keep making more insulin to clear the extra sugar. Here we look at the role inflammation plays. We also look at why it might be the most important force fueling the diabesity epidemic.
Why are anti-inflammatory drugs not the mainstay of diabetes type 2 treatment?
Before getting into the meat of the diabesity-inflammation pendulum, here is 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.”
So why are anti-inflammatory drugs not the main treatment for type 2 diabetes? This is a hot debate. But it is believed that sodium salicylate was dropped because of the serious side effects it causes at high doses.
Now we can look at how diabesity and inflammation swing back and forth.
How does Inflammation Cause Diabesity?
Several lines of evidence link inflammation with obesity and diabetes. Here are a few:
- Inflammatory markers are elevated prior to diabesity.
High levels of inflammatory cytokines could indicate future weight gain and obesity. A lab study also gave healthy mice an infusion (a slow drip) of these cytokines. It showed that this causes insulin resistance.
Another fact backs this up. People with other long-term inflammatory conditions are more likely to get diabesity and type 2 diabetes.
- Inflammation causes insulin resistance
Inflammation of fat tissue causes insulin resistance, which is the main cause of diabesity. A small protein called TNF-α is released during inflammation. It 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.
- Inflammation in the brain causes leptin resistance
Inflammatory signaling in the hypothalamus (the brain’s control center for hunger) has been linked to leptin resistance in both animals and humans. Leptin is made in fat cells, but it does most of its work in the hypothalamus. It is the starvation hormone, but it is also called the obesity hormone. Leptin resistance means your body no longer responds to leptin. When this happens, your brain is fooled into thinking you are starving. So you keep eating more and more food. In the end, this leads to diabesity.
How Does Diabesity Cause Inflammation?
For a long time, people believed fat was inert tissue that did nothing. Now we know fat is a metabolically active endocrine organ. It makes hormones and inflammatory molecules. This is the key to understanding the role of fat in diabesity and inflammation.
- Diabesity induces inflammation as a protective mechanism.
Diabesity causes fat to build up around the waist. Storing fat is an anabolic (building) process, while inflammation is a catabolic (breaking down) process. The body may switch on catabolism through inflammation to keep weight within acceptable limits. In experiments, inflammation set off in fat tissue has been shown to start weight loss and improve insulin resistance.
- Diabesity related stresses could cause inflammation
Obesity has been associated with chronic low-level inflammation. One hypothesis is that the stresses of diabesity are like the stresses of an infection. So the body responds the same 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
Clearly there is a direct relationship between diabesity and inflammation. But it is not very clear which one comes first. Inflammation is both the cause and the result of diabesity. Inflammation plays a big role in causing diabesity. In turn, diabesity can push the body to make even more inflammatory cytokines. That forms a vicious cycle of inflammation and diabesity.
So we can say with confidence what the best way to treat or prevent diabesity is. It has to start by addressing the inflammation underneath. Treatment should also go after inflammation once diabesity has set in. The modern clinical approach focuses on regulating blood sugar without addressing inflammation. Sadly, that approach is bound to produce worse results.
Related reading
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
Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP
Interventional pain physician, addiction medicine specialist and obesity medicine diplomate.
Licensed in Missouri and Illinois.
Last reviewed November 19, 2019
