Brain Link Established Between Stress and Type 2 Diabetes

According to the American Diabetes Association (ADA), more than 20 million people in the US are diagnosed with some form of diabetes, a metabolic condition in which the body is unable to produce enough of the hormone insulin to regulate glucose levels in the blood. Only about 1.25 million have Type 1, sometimes called “juvenile” diabetes, the auto-immune form of the disease that kills off the special cells that produce insulin. The vast majority of diabetics have Type 2, the insulin-resistant variety of the disease, where the body simply doesn’t make enough insulin to deal with glucose properly. Many older, overweight people develop Type 2 diabetes, but doctors still don’t fully understand why many others in the same condition do not. A new study out of Rice University offers another clue, establishing links between emotional stress, inflammation, and Type 2 diabetes.

Microbes working with and against the body

Over the past few years, neuroscientists and clinicians alike have become more interested in the so-called microbiome, or the glut of bacteria and other microorganisms that live inside the human gut, and how it influences behavior and disease states (See ” The Brain-Gut Axis and Neuropsychiatric Disease: A Paradigm Shift”). Many studies now suggest that stress alters the diversity of gut bacteria, and makes people more susceptible to mood and anxiety disorders. Such stress changes may also extend to other common disease states, including diabetes.

Joe Alcock, a physician at the University of New Mexico department of emergency medicine, says it’s becoming apparent that the gut microbes are an integral part of human physiology and health. Our gut bacteria have co-evolved along with humans, and that co-evolution, along with work that shows the importance of gut bacteria to good health, suggests a certain symbiosis or mutualism. But Alcock’s work with Athena Atkipis, a psychologist at Arizona State University, suggests our microbiome is not always working toward our best interests. In some instances, such as situations of chronic stress, they may actually work in conflict and, directly and indirectly, facilitate major health problems. Those ideas were published in the May 2016 issue of the Annals of the New York Academy of Sciences.

“We’ve made this assumption that if we co-evolved along with these microbes they must be doing something good for us, that there’s a somewhat perfect harmony between us and our resident microbes,” he says. “But there also seems to be conflict. And we can infer that conflict in some of the negative health outcomes we see like obesity, chronic inflammation, overgrowth of pathogens, direct invasion of microbes into our bodies, and diabetes. And that conflict may occur in response to things like stress, where stress hormones actually make it easier for harmful microbes to take over. So we need to better understand how these microbes are working to both help and hurt health outcomes.”

Several studies have now shown that stress can reduce the diversity in the microbiome–and, vice versa, such a lack of bacterial diversity can also influence brain states and behavior. Such microbiome “conflicts” may have the power to negatively affect brain function, including processes such as inhibition and attentional control.

Stress, anxiety, and diabetes

Christopher Fagundes, a psychologist at Rice University, has long been interested in how stress affects the immune system. He and his post-doctoral fellow, Kyle Murdock, say that it’s long been known that anxiety and stress are linked to poor health outcomes, including the development of Type 2 diabetes—but the why’s weren’t well understood.

“Past studies have shown that individuals with poor inhibition, or attentional control, are more likely to experience a lot of stress and anxiety,” says Murdock. “And it made me wonder if there was some stress-induced pathway that could link inhibition with inflammation and then on to diabetes. So we decided to take a look at it.”

He and Fagundes examined health and cognitive data from more than 800 middle-aged adults who were tested twice over a period of two years. Included were cognitive and psychological batteries, as well as interleukin-6 (IL-6) measures, a common measure of stress and inflammation, and glucose levels. Volunteers who exhibited low inhibition (by being more vulnerable to distraction on cognitive tasks) were more likely to have more anxiety, have more inflammation as measured by IL-6 levels, and, consequently, go on to develop diabetes. The researchers did not find a bi-directional link, however—inflammation levels did not increase inhibition. A lack in the brain’s executive functioning seemed to lead to the kind of inflammation that led to disease. The results were published on May 18, 2016, in Psychoneuroendocrinology.

“Inflammation, in the short term, at least, is a good thing. It’s an important immune function that can help clear the bacteria out of wounds and so forth. But when you have chronically high levels of inflammation, which we know that stress is related to, people are more likely to go on to have a host of different diseases, including diabetes,” says Fagundes. “So we see this really important pathway from inhibition to anxiety to inflammation and then to diabetes. And even when you adjust for health behaviors like diet and exercise, stress seems to have an impact over and above all that, which is important not only to understand who may develop diabetes but why particular individuals may have difficulty managing these kinds of conditions once they get them.”

The microbiome and medicine

This link between executive functioning, inflammation, and disease provides clinicians a unique opportunity to help people prevent, or at least more effectively manage, conditions like obesity and diabetes in the future, including with novel therapies, Fagundes says.

“Maybe it’s not just about diet and exercise. We may be able to do bio-behavioral interventions that target executive functioning to change levels of inflammation. We could do mindfulness training that helps lower stress and inflammation,” says Fagundes. “There is also an implication for pharmaceuticals. You can imagine a scenario where you can use some kind of stimulant to improve inhibition and ultimately help inflammation which might help, too.”

While he and Murdock did not look at microbiome changes in this study, he thinks that scientists need to take a multi-disciplinary, bio-behavioral approach to assess people’s psychological health as well as their physiology to better understand the root of modern diseases. Changes to the microbiome could be a part of that assessment.

Alcock agrees. Physicians need to be more educated about the links between the microbiome, stress, and various health outcomes so they can do a better job of treating patients—and, perhaps, preventing the onset of common chronic diseases like Type 2 diabetes, he says.

“When I went to medical school, we didn’t learn anything about the microbiome. And it’s exciting to recognize that these microbes can have such a profound effect on health,” he says. “The idea that stress, microbes and disease are linked is a really interesting one. Every day I work in the emergency room, I have to make decisions about how to treat people. So I hope, in the future, medical students learn more about not only physiology, but all the things that cause diabetes and promote obesity, so we can do a better job of treating people and promoting good health.”