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Better understanding the link between inflammation and diabetes

Inflammation is the general term for the increased activity of the immune system cells and other cells. The normal immune response to infection can protect and heal the body. When we break a bone, the area swells as the body works to repair itself. The immune system also becomes inflamed in response to cold and flu as the immune system’s way to protect us. “It’s a way of dealing with things you want to get rid of,” says Dr. Kevan Herold, Yale Medicine endocrinologist.

But sometimes, inflammation can negatively impact the body. That’s the case with diabetes. When people develop type 1 diabetes, the immune cells are randomly activated and attack the insulin-producing beta cells in the pancreas, Herold says. This could classify as inflammation. Researchers now believe the body’s immune system gradually kills beta cells, and type 1 diabetes “develops over a period of years,” says Herold, also a professor of immunobiology and medicine at Yale School of Medicine. The remaining beta cells continue to produce insulin and work overtime to make up for the loss of their sibling cells. But eventually, when it progresses to the point of overpowering the still-functioning beta cells’ ability to produce insulin, the disease becomes acute with extreme thirst, fatigue and frequent urination. 

Some people receiving medications called checkpoint inhibitors to fight cancer develop type 1 diabetes. In those individuals, there is clear inflammation in the pancreas, Herold says. Checkpoint inhibitors block the body’s immune response to activate the cells capable of killing tumors, but sometimes the cells capable of killing the insulin-producing cells in the pancreas also get triggered.

Endocrinologists have long suspected a virus ignites type 1 diabetes in those who carry the gene for the chronic disease, but there’s now debate among researchers about the validity of that theory, Herold says. “There is no 100 percent convincing data yet.” One new piece of evidence to consider is the increase in people developing type 1 diabetes after getting COVID-19. To fight COVID, the body’s immune cells ramp up, which is a type of inflammation, he says. “There were a lot of new cases of diabetes in children who developed COVID. Many were probably on their way to developing diabetes and the COVID was the last straw that broke the camel’s back,” he says. 

Ongoing inflammation, called chronic inflammation, can be detrimental to your health, especially because it often goes undetected for months or years. Doctors can check for internal inflammation by measuring for higher levels of biomarkers, such as C-reactive protein (CRP). Those with cancer, obesity and who are older tend to have higher CRP levels. Tissue damage from chronic inflammation can increase your risk of type 2 diabetes, heart disease and metabolic syndrome, cancer, allergies, arthritis and psoriasis, some autoimmune conditions, such as rheumatoid arthritis and neurological diseases like dementia. Type 2 diabetes, a chronic disease, develops when the body has difficulty processing glucose, or blood sugar, from carbohydrates in food.

It’s kind of a catch-22. Obesity is associated with increased inflammation, and weight loss and exercise can help reduce diabetes risk, Herold says. But having chronic inflammation can make it difficult to lose weight. There are drugs, called glucagon-like peptide 1 (GLP-1), that stimulate a molecule that seems to be important to metabolism. These medications, including exenatide, liraglutide and lixisenatide, “lead to weight loss and actually do lessen inflammation,” he says, referring to a 2017 study in Diabetes Spectrum.

Chronic inflammation can lower the body’s immunity and cause tissue damage that also puts people at greater risk for brain fog, indigestion and fatigue. While scientists are still studying factors that lead to chronic inflammation, it’s believed to be a mix of things out of our control (infections and genes) and within our control (what we eat and how regularly we exercise). When the body experiences chronically high blood sugar levels, it triggers the body’s inflammatory response. Inflammation gets people two ways: it plays a role in developing type 2 diabetes to begin with, and contributes to its progression, studies have found. 

“Anything that’s proinflammatory isn’t great for any of the tissues in our body,” says Michael Stitzel, associate professor at The Jackson Laboratory. Every human being is different, and one current thought, he says, “is each of us is born with a certain amount of insulin-producing cells. My reservoir may be lower than yours to start. … Then we have environmental factors like eating junk food and not exercising, which contributes to an increase in obesity and insulin resistance.” 

Adipose, or fat, tissue delivers a strong signal to the other tissues within the body and can induce an inflammatory response, Stitzel says, but not all inflammation that occurs within the body is activated by obesity. Whether we have diabetes or not, when we eat a fatty meal or drink alcohol, that causes an inflammatory response, he says. When our bodies metabolize alcohol, there can be damage to the liver that ignites inflammation. Scientists are still studying the molecules that contribute to inflammation, he says. “We’re trying to understand what these switches are controlling.”

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