Research & Publications †
( † Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)
John P. Kirwan, PhD, heads a team that conducts clinical translational research in aging, obesity and diabetes. Specific research studies are currently examining:
Aging and Insulin Resistance:
We are examining how exercise and nutrition alter disease risk associated with insulin resistance, obesity and type 2 diabetes in older adults. This is an NIH-funded clinical trial to determine how aerobic exercise training and nutrition interventions, including high and low glycemic diets, may reverse insulin resistance. These studies are designed to investigate the physiological and cellular mechanisms by which alterations in life-style factors such as exercise and nutrition can improve metabolic control and body composition in older men and women. This study is open to enrollment for overweight men and women, 60 years of age and older.
Exercise and Insulin Resistance in Skeletal Muscle:
Exercise training is typically associated with enhanced insulin sensitivity and is used as a first-line treatment for age-related diseases such as type 2 diabetes. We have shown that heightened insulin sensitivity is mediated by increased post-receptor insulin signaling, specifically at the distal steps of the insulin/PI 3-kinase signaling cascade that leads to GLUT-4 translocation and glucose uptake. It should be stated that the majority of human studies, including our own, have been performed on young healthy individuals. We are currently examining whether the same holds true for older adults with impaired glucose tolerance or type 2 diabetes.
Fatty Liver Disease and Insulin Resistance:
There is a growing body of evidence that an accumulation of fat in vital organs outside of the adipose tissue depots may be one of the driving mechanisms behind the development of insulin resistance and type 2 diabetes. This accumulation is particularly problematic in the liver, because it may contribute to hepatic insulin resistance and hyperglycemia. Recent clinical data suggest that up to 70% of patients with type 2 diabetes have sufficient accumulation of fat in the liver to warrant diagnosis of nonalcoholic fatty liver disease (NAFLD), a disease that may advance to steatosis, fibrosis, cirrhosis and death. We are currently exploring the use of magnetic resonance imaging and spectroscopy techniques to noninvasively and comprehensively characterize hepatic lipids. We plan to use these tools in intervention studies in patients with NAFLD and NASH with the goal of identifying effective treatment strategies for reversing and preventing steatosis.
Obesity and Insulin Resistance:
Obesity is a major contributing factor to insulin resistance and type 2 diabetes. Bariatric surgery is a widely used therapy for those with a body mass index (BMI) greater than 40, or a BMI >35 in the presence of significant comorbidities. Certain bariatric surgery procedures are associated with remission of diabetes, and this may occur within days after surgery. We are currently examining the effects of various GI surgical procedures on insulin resistance, insulin secretion and hepatic glucose output in human and animal studies. We are measuring gut hormones that may have modulating effects on glucose metabolism with the goal of identifying new therapeutic targets for the treatment of obesity, insulin resistance and type 2 diabetes.
exercise physiology, insulin resistance, Metabolic Syndrome, Obesity
Molecular biology, University of California, San Diego
Cleveland Clinic physicians and scientists may collaborate with the pharmaceutical or medical device industries to help develop medical breakthroughs or provide medical expertise or education. Cleveland Clinic strives to make scientific advances that will benefit patient care and support outside relationships that promise public benefit. In order for the discoveries of Cleveland Clinic physicians' and scientists' laboratories and investigations to benefit the public, these discoveries must be commercialized in partnership with industry. As experts in their fields, Cleveland Clinic physicians and scientists are often sought after by industry to consult, provide expertise and education.
To assure professional and commercial integrity in such matters, Cleveland Clinic maintains a program that reviews these collaborations and, when appropriate, puts measures in place to minimize bias that may result from ties to industry. Cleveland Clinic publicly discloses the names of companies when (i) its physicians/scientists receive $5,000 or more per year (or, in rare cases, equity or stock options) for speaking and consulting, (ii) its physicians/scientists serve as a fiduciary, (iii) its physicians/scientists
receive or have the right to receive royalties or (iv) its physicians/scientists hold any equity interest for the physician's/scientist's role as inventor, discoverer, developer, founder or consultant.* In publicly disclosing this information, Cleveland Clinic tries to provide information as accurately as possible about its physicians' and scientists' connections with industry.
As of 2/20/2016, Dr. Kirwan has reported no financial relationship with industry that is applicable to this listing. In general, patients should feel free to contact their doctor about any of the relationships and how the relationships are overseen by Cleveland Clinic. To learn more about Cleveland Clinic's policies on collaborations with industry and innovation management, go to our Integrity in Innovation page.
Public Health Service-Reportable Financial Conflicts of Interest. Cleveland Clinic scientists and physicians engage in basic, translational and clinical research activities, working to solve health problems, enhance patient care and improve quality of life for patients. Interactions with industry are essential to bringing the researchers’ discoveries to the public, but can present the potential for conflicts of interest related to their research activities. Click here to view a listing of instances where Cleveland Clinic has identified a Public Health Service (PHS)-Reportable Financial Conflict of Interest and has put measures in place to ensure that, to the extent possible, the design, conduct and reporting of the research is free from bias. * Cleveland Clinic physicians and scientists subscribe to the guidance presented in the PhRMA Code on Interactions with Healthcare Professionals and the AdvaMed Code of Ethics on Interactions with Health Care Professionals. As such, gifts of substantial value are generally prohibited.