Research & Publications †
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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
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As of 2/24/2015, 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.
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