This week a group of interdisciplinary researchers from the University of Toronto (UT) released study findings in which they made an important discovery in the field of Obesity Medicine.  The study entitled, “Regulation of Obesity-Related Insulin Resistance with Gut Anti-inflammatory Agents,” used an animal model to provide evidence that altered gut immunity in obesity contributes to obesity-related insulin resistance (IR), and that it may be possible to use Mesalamine, a drug for treating Crohn’s disease, as a new therapeutic approach for diabetic patients.  The study was published in the latest on-line edition of Cell Metabolism.

Background Terminology:

• Insulin: a hormone that regulates the movement of sugar into your cells.
• Insulin Resistance (IR): is a condition in which the body produces insulin but does not use it effectively. When patients have insulin resistance, glucose builds up in the blood instead of being absorbed by the cells, leading to type 2 diabetes or prediabetes.
• Type 2 Diabetes: a chronic condition in which a patient’s body either resists the effects of insulin or doesn’t produce enough insulin to maintain a normal glucose level.

This Study:

The study was conducted in the laboratory of Dr. Daniel Winer, MD, Endocrine Pathologist, Assistant Professor, Department of Laboratory Medicine and Pathobiology, Department of Immunology, Department of Endocrinology, UT.  The goal of his laboratory is to better understand how the immune system influences physiological processes and contributes to disease, with the aim of creating new treatment options for patients diagnosed with these diseases.

Dr. Winer was the winner of the prestigious Benjamin Castleman Award, in 2012 for the work he and his laboratory colleagues undertook in which they demonstrated that immune cells inside abdominal fat cause the release of ‘pro-inflammatory’ chemicals, which make the body less sensitive to insulin, and possibly trigger type 2 diabetes.  Building upon this previous work, the lab shifted focus from studying the adipose tissue to what was going on in the gut.  They did this by observing the effect of a high-fat, high-calorie diet on the immune cells in the bowel of mice.

The Results:

The results showed that the mice fed this type of diet had larger amounts of pro-inflammatory immune cells and less of the regulating cells which help end an immune response than mice that were fed a normal diet. This increase in pro-inflammatory immune cells induced inflammatory changes in the immune cells in the bowel, upsetting the immune balance, which initiated a domino effect that damaged the bowel wall, allowing bacterial products to leak into the blood stream.  This leakage is a main contributor to IR.  The same findings were observed when the researchers studied the immunologic components of 14 human subjects, 7 of whom were obese.

In a press release about the importance of the study, Dr. Winer, stated, “These results are novel and important because we have identified the immune system that lives in the gut as a new player in the control of blood sugar. This opens up the entire field of bowel immunology to the study of obesity and its complications such as high blood sugar.”

Upon identification of the importance the immune system plays in this process, the researchers sought to treat the inflammation and in an experimental test gave the obese mice mesalamine.  They found that the drug reversed IR and lowered blood sugar significantly in the mice to near normal levels.

Dr. Winer explained that, “By using this drug, we found that we could prevent type 2 diabetes in mice. If this works in humans, it could change the whole field of diabetes prevention and treatment.”

These study findings are of particular importance in the US, since obesity rates in this country are currently at epidemic levels and are strongly associated with severe health and economic impacts.  It has been said that obesity now costs Americans more in healthcare spending than smoking. In 2010, the Congressional Budget Office reported that nearly 20 percent of the increase in U.S. health care spending (from 1987-2007) was caused by obesity. Annual health costs related to obesity in the U.S. comes with a nearly $200 billion price tag, and nearly 21 percent of medical costs in the U.S. can be attributed to obesity.