An associate professor in the University of Arizona Division of Endocrinology and Department of Physiology, Dawn Coletta, PhD, received an Innovative Clinical or Translational Science Award from the American Diabetes Association (ADA) for a three-year, $600,000 study titled “Unraveling the role of mitochondrial DNA methylation in type 2 diabetes.”
The issue this study addresses involves people who are obese or who have type 2 diabetes and are insulin resistant. Insulin resistance is a state when your body is not using insulin correctly, and more insulin is needed to keep blood sugar levels normal. People with insulin resistance have mitochondria, a part of cells that produces energy, which are impaired and do not work well in muscle.
EXTRA INFO: Fast Facts on Diabetes
Of more than 30 million Americans with diabetes (about 1 in 10), 90 to 95 percent of them have type 2 diabetes. Type 2 diabetes most often develops in people over age 45, but more and more children, teens, and young adults also are developing it, according to the U.S. Centers for Disease Control and Prevention. Effective lifestyle changes, however, can prevent that. For related information and factsheets, click here: CDC | NIH | ACP | ADA | HealthLine.
The ADA reports the total U.S. economic burden of diagnosed diabetes in 2017 was $327 billion—$237 billion in direct costs and $90 billion in reduced productivity.
- Health care costs for those with diagnosed diabetes are 2.3 times more than others
- 1-in-7 health-care dollars is spent treating diabetes and its complications
- 1-in-5 health-care dollars is spent caring for people with diabetes
- The average price of insulin nearly tripled between 2002 and 2013
- Annually, 50,100 Americans begin treatment for kidney failure due to diabetes
- Hearing loss is about twice as common in adults with diabetes as those without it
- 60 percent of non-traumatic lower-limb amputations (108,000 yearly) occur in people with diabetes
Dr. Coletta's study will determine whether DNA methylation—a normal chemical process in the body that modifies DNA of the genes coding for mitochondria function—can explain the impairment that results in insulin resistance observed in muscle of type 2 diabetic patients.
DNA methylation is a process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription as an epigenetic signaling tool that can fix genes in the “off” position.
More recently, genetic sequencing and methylation analyses have been used as a biomarker to predict patients at risk of developing diabetes or specific complications of diabetes. This identification and understanding of epigenetic changes (including DNA methylation) in mitochondrial DNA in insulin-resistant skeletal muscle may lead to novel treatments for type 2 diabetes, Dr. Coletta said.
“If we show that there is methylation at the mitochondrial DNA, and that it does contribute to the impaired mitochondrial function in type 2 diabetes, then it could open the window to investigating therapies or treatments” to attempt to correct it, she added. Currently, there are no existing/potential therapies to address this.
As the award is a clinical translational grant, her research team will recruit participants through the UA Health Sciences Clinical and Translational Sciences Research Center (CaTS). With UA Institutional Review Board (IRB) approval, participants will undergo screening and euglycemic-hyperinsulinemic clamps with muscle biopsies. The muscle biopsies will be analyzed in Dr. Coletta' lab to determine and measure mitochondrial methylation and mitochondrial function.
Co-investigators on the study include Wayne Willis, PhD, an associate professor in the Division of Endocrinology, and Endocrinology Division Chief Lawrence Mandarino, PhD, and Janet Funk, MD, a professor of medicine in the Division of Endocrinology and nutritional sciences in the UA College of Agriculture and Life Sciences. Dr. Funk is handling the clinical portion of the study, which has already begun recruiting.
Dr. Coletta joined the UA College of Medicine – Tucson faculty in 2016. She earned her bachelor’s degree in applied and human biology from the Aston University School of Life and Health Sciences in Birmingham, England (1999) and got her doctorate there in 2003. Her thesis was on “Interventions against obesity through increased lipolysis of adipose tissue.”
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