Mathur, Ruchi , MD
Methane production and glycemic regulation in prediabetic subjects: Role of methane in glycemic control
General Research Subject: Insulin Resistance Pre Diabetes
Focus: Insulin Action\Insulin Resistance, Insulin Action\Metabolism, Obesity\Pathogenesis
Type of Grant: Innovation
Project Start Date: January 1, 2012
Project End Date: December 31, 2013
Diabetes is a serious and rapidly increasing health problem. Almost 24 million Americans have diabetes, which is a significant cause of heart disease and stroke, high blood pressure, blindness, kidney disease, diseases of the nervous system, and amputations. Significantly, a further 57 million Americans have prediabetes, and while the factors that predispose certain individuals towards developing diabetes are poorly understood, obesity is known to be a significant contributing factor. Our studies have shown that certain types of bacteria in the gut may directly affect weight gain. These bacteria (called methanogens) produce methane, which can slow the passage of food through the intestines, allowing greater time for nutrient absorption. Significantly, we found that people who have increased levels of methane-producing bacteria in their intestines have higher body weights, and higher levels of glucose in their blood. Therefore, control of how the body responds to insulin and uses glucose may be altered in methane-producing individuals. In this application, we propose to study how methanogens and methane gas affect the gut, particularly food transit through the gut, to determine how they may contribute to the development of diabetes. We will first study the response to insulin, gut transit, body fat distribution, and levels of lipids, hormones and other factors in obese, prediabetic methane-producing individuals. Next, we will re-examine all of these parameters in methane-producing individuals after treating them with antibiotics that eliminate methanogens. This may allow us to begin to develop treatments to reduce methanogen infection and insulin resistance in individuals with prediabetes.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This project explores factors predisposing to the development of obesity, which is known to be a significant risk factor for the development of diabetes. Specifically, it is becoming increasingly understood that the presence of certain types of bacteria in the gut, particularly those that produce methane (methanogens), may directly affect weight gain. Methane can slow the passage of food through the intestines, allowing greater time for nutrient absorption. Significantly, we found that people who have increased levels of methane-producing bacteria in their intestines have higher body weights, and higher levels of glucose in their blood. In this project we propose to study how intestinal methanogens and their byproduct, methane gas, affect the gut. We are particularly interested in the effect on food transit through the gut, to determine how this may contribute to the development of obesity and pre-diabetes. Understanding this relationship better may allow us to begin to develop treatments to reduce methanogen colonization in the intestine and ultimately benefit individuals with obesity and prediabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
The studies we will perform will allow us to develop a much better understanding of how the presence of higher levels of intestinal microbes, especially methanogens affect transit of food through the gut, nutrient absorption from food, and response to insulin in affected individuals, all of which may contribute to weight gain. This may explain why certain individuals have difficulty losing weight using conventional approaches such as diet and exercise. Further, by testing whether gut transit, nutrient absorption and response to insulin can be changed by treating these individuals with specific antibiotics, this research may allow us to develop effective treatments for some people with obesity and prediabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Personally, it amazes me that we have a disease that touches such a large population of humanity, and we are still trying to understand it at such a basic level. I really believe that diabetes is does not simply stop at type 1 and type 2, but that there are many different causes of diabetes that we are just starting to explore. This award will allow our research team to look at yet another possible contributor to diabetes and obesity. It will allow us to explore possibilities down a road that is much less travelled than others, but which might offer significant insights into obesity, prediabetes and diabetes.
In what direction do you see the future of diabetes research going?
I hope research in diabetes moves towards a multidisciplinary approach. We need minds that are expert in other areas of human biology, physiology and understanding to join in the search for answers. Someone once said "It takes a village...." And diabetes research is no exception.
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