A conversation with John P. Kirwan, PhD

John Kirwan
John P. Kirwan

John P. Kirwan, PhD, director of the Metabolic Translation Research Center and professor of molecular medicine at Cleveland Clinic, has been named executive director of the Pennington Biomedical Research Center at Louisiana State University. Kirwan’s career has centered on biomedical research in diabetes, obesity, nutrition and exercise.

Kirwan spoke with Endocrine Today about his interests in bariatric surgery and its effect on type 2 diabetes, transgenerational obesity and “exercise in a pill.”

What area of endocrinology most interests you right now and why?

Kirwan: I am intensely interested in three specific areas at this time. The first is bariatric surgery because of its profound effect on type 2 diabetes. Not only are we discovering that bariatric surgery has the ability to reverse type 2 diabetes in over 75% of the cases, but we are also seeing that it can reduce hypertension and the overall medication burden on diabetic patients. There are risks to surgery, of course, so we are also assessing long-term safety outcomes.

The second area I’m particularly interested in is transgenerational obesity and potential solutions to break the obesity cycle. Mothers with overweight or obesity typically transfer the obesity to their babies, these babies then have a greater likelihood of becoming obese adults and experience health issues related to obesity. I am currently the co-principal investigator on a 5-year grant from the National Institute of Child Health and Human Development of the NIH that aims to test an approach that will prevent this problem. LIPP (Lifestyle Intervention in Preparation for Pregnancy) is a first-of-its-kind lifestyle intervention that introduces a diet and exercise program before conception. Similar interventions that start after conception tend to have limited success. I’m also thrilled to now be involved with Pennington Biomedical Research Center studies that use the world’s only functioning infant metabolic chamber. The chamber is an integral part of the IMAGINE research study at Pennington Biomedical that will assess how a pregnant mother’s metabolism may set the stage for her child’s future health.

Third, we understand that exercise improves glucose control in individuals with type 2 diabetes, but we are not sure exactly how the effect works. While searching for the answer, we discovered proteins secreted from the skeletal muscle in response to exercise that trigger pancreatic beta cells to secrete insulin more effectively. This discovery has helped us to identify how exercise helps patients with diabetes. More importantly, this information has given us the data we need to replicate that effect in the body with drug therapy — instead of depending on skeletal-muscle signaling. Simply, it will help us design an “exercise in a pill” for those who cannot easily incorporate exercise into their daily lives.

What do you think will have the greatest influence on your field in the next 10 years?

Kirwan: I believe precision medicine will have a great influence on health care within the next 10 years. This will enable clinicians to use individual profiles to target treatments that are specific to the individual and their condition. Currently, the NIH’s All of Us Research Program is gathering data from a diverse group of 1 million or more trial participants. The enormity of this data set, and the discoveries which will follow, will help us deliver more targeted treatments and maximize each patient’s ability to live a healthy life — which has the potential to reduce both unnecessary care and costs.

Another wave of change will likely come from the discoveries we will find in the microbiome studies, such as the NIH’s Human Microbiome Project. These studies are producing data resources for researchers seeking to understand the effect of the human microbiome on health, as well as for clinical scientists who are testing new therapies to impact the microbiome in ways that enhance health overall.

What are some of the most exciting advances that you have been a part of?

Kirwan: The discovery that bariatric surgery has the ability to put type 2 diabetes into remission is one of the most important breakthroughs that comes to mind. It’s gratifying to know that I worked on a team that shed light on a new, successful treatment option for patients with diabetes.

What advice would you offer to a student going into endocrinology today?

Kirwan: I’d recommend students find the area of science that ignites a passion and motivation within that will fuel a lifelong journey of discovery, despite the inevitable setbacks and challenges. To me, it’s also essential to find a mentor you can work with and a supportive environment like Pennington Biomedical Research Center that provides the resources needed to flourish as a scientist.

What are your hobbies and interests outside of work?

Kirwan: My family is a central focus for my time outside of work. I also enjoy athletics of any kind, especially football and soccer. For an evening away from it all, I turn to the arts. The symphony and theatre are always useful for regenerating the creative spark. – compiled by Amber Cox

John Kirwan
John P. Kirwan

John P. Kirwan, PhD, director of the Metabolic Translation Research Center and professor of molecular medicine at Cleveland Clinic, has been named executive director of the Pennington Biomedical Research Center at Louisiana State University. Kirwan’s career has centered on biomedical research in diabetes, obesity, nutrition and exercise.

Kirwan spoke with Endocrine Today about his interests in bariatric surgery and its effect on type 2 diabetes, transgenerational obesity and “exercise in a pill.”

What area of endocrinology most interests you right now and why?

Kirwan: I am intensely interested in three specific areas at this time. The first is bariatric surgery because of its profound effect on type 2 diabetes. Not only are we discovering that bariatric surgery has the ability to reverse type 2 diabetes in over 75% of the cases, but we are also seeing that it can reduce hypertension and the overall medication burden on diabetic patients. There are risks to surgery, of course, so we are also assessing long-term safety outcomes.

The second area I’m particularly interested in is transgenerational obesity and potential solutions to break the obesity cycle. Mothers with overweight or obesity typically transfer the obesity to their babies, these babies then have a greater likelihood of becoming obese adults and experience health issues related to obesity. I am currently the co-principal investigator on a 5-year grant from the National Institute of Child Health and Human Development of the NIH that aims to test an approach that will prevent this problem. LIPP (Lifestyle Intervention in Preparation for Pregnancy) is a first-of-its-kind lifestyle intervention that introduces a diet and exercise program before conception. Similar interventions that start after conception tend to have limited success. I’m also thrilled to now be involved with Pennington Biomedical Research Center studies that use the world’s only functioning infant metabolic chamber. The chamber is an integral part of the IMAGINE research study at Pennington Biomedical that will assess how a pregnant mother’s metabolism may set the stage for her child’s future health.

Third, we understand that exercise improves glucose control in individuals with type 2 diabetes, but we are not sure exactly how the effect works. While searching for the answer, we discovered proteins secreted from the skeletal muscle in response to exercise that trigger pancreatic beta cells to secrete insulin more effectively. This discovery has helped us to identify how exercise helps patients with diabetes. More importantly, this information has given us the data we need to replicate that effect in the body with drug therapy — instead of depending on skeletal-muscle signaling. Simply, it will help us design an “exercise in a pill” for those who cannot easily incorporate exercise into their daily lives.

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What do you think will have the greatest influence on your field in the next 10 years?

Kirwan: I believe precision medicine will have a great influence on health care within the next 10 years. This will enable clinicians to use individual profiles to target treatments that are specific to the individual and their condition. Currently, the NIH’s All of Us Research Program is gathering data from a diverse group of 1 million or more trial participants. The enormity of this data set, and the discoveries which will follow, will help us deliver more targeted treatments and maximize each patient’s ability to live a healthy life — which has the potential to reduce both unnecessary care and costs.

Another wave of change will likely come from the discoveries we will find in the microbiome studies, such as the NIH’s Human Microbiome Project. These studies are producing data resources for researchers seeking to understand the effect of the human microbiome on health, as well as for clinical scientists who are testing new therapies to impact the microbiome in ways that enhance health overall.

What are some of the most exciting advances that you have been a part of?

Kirwan: The discovery that bariatric surgery has the ability to put type 2 diabetes into remission is one of the most important breakthroughs that comes to mind. It’s gratifying to know that I worked on a team that shed light on a new, successful treatment option for patients with diabetes.

What advice would you offer to a student going into endocrinology today?

Kirwan: I’d recommend students find the area of science that ignites a passion and motivation within that will fuel a lifelong journey of discovery, despite the inevitable setbacks and challenges. To me, it’s also essential to find a mentor you can work with and a supportive environment like Pennington Biomedical Research Center that provides the resources needed to flourish as a scientist.

What are your hobbies and interests outside of work?

Kirwan: My family is a central focus for my time outside of work. I also enjoy athletics of any kind, especially football and soccer. For an evening away from it all, I turn to the arts. The symphony and theatre are always useful for regenerating the creative spark. – compiled by Amber Cox