University of Michigan Health System researchers will use a $3.5 million federal grant to study a new approach in halting the downward spiral of diabetes.

The complications of diabetes, from poor vision and nerve damage to kidney failure, contribute to a poor quality of life and higher death rate for the 25.8 million adults and children in the United States who are diabetic.

The National Institute of Diabetes and Digestive and Kidney Diseases will fund the U-M’s work to examine tissue-specific metabolic reprogramming in diabetes complications.

“To date, no attempt has been made to systemically understand the energy metabolism abnormalities in these tissues in type 1 diabetes, or to link these abnormalities to complications progressions,” says study principal investigator and kidney specialist Frank C. Brosius III, M.D., chief of the U-M Department of Nephrology.

Just as diabetes impacts several systems of the body, the U-M research team represents a varied group of experts including specialists in neurology, nephrology and retinopathy.

Brosius, along with diabetes and obesity specialist Charles Burant, M.D., Ph.D.; neurologist Eva L. Feldman, M.D., Ph.D.; ophthalmologist Thomas W. Gardner, M.D., M.S., of the U-M’s Kellogg Eye Center and assistant professor of internal medicine Subramaniam Pennathur, M.B.B.S., will lead the consortium of investigators.

“This research challenges the theory that diabetic complications are simply driven by excessive glucose and provides novel understanding of the metabolic basis of diabetic complications,” says Burant, professor of internal medicine, molecular and integrative physiology and Director of the Michigan Metabolomics and Obesity Center.

The U-M team proposes that diabetes disrupts basic metabolic pathways in complication-prone tissues and that understanding these altered pathways will provide new targets for drug therapies that could prevent or treat diabetes complications.
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Metabolic reprogramming diabetes complications – add 1
Diabetes is diagnosed when the body has an abnormally high level of glucose, or blood sugar. Researchers will focus on type 1 diabetes, the less common but unpreventable form of diabetes.

In type 1, the body’s immune system destroys the pancreatic beta cells responsible for making insulin, a hormone the body needs to convert food into energy. Type 1 diabetes usually strikes children and young adults, compared to type 2 diabetes which is associated with older age, obesity and family history.

Those with diabetes and their primary care providers are familiar with the potential for developing complications.
Diabetic retinopathy is a major cause of preventable vision loss among work age adults in developing countries.

Diabetic peripheral neuropathy is one of the most common complications of diabetes and occurs over time in approximately 60 percent of all patients with diabetes. DPN puts them at higher risk for lower limb amputation.

But few options are available for successfully preventing these complications besides tight glucose control.

“Fundamentally new approaches are needed to understand the metabolic abnormalities that lead to diabetic complications and develop effective treatment or prevention strategies,” says Gardner, one of a nine-member research team on diabetes-related eye disease that was recruited to join Kellogg in 2010.

The U-M provides remarkable strength in diabetes research. Its major diabetes research program is housed at the Brehm Center for Diabetes Research – a partner of the U-M Comprehensive Diabetes Center – and brings together faculty who are experts in all complications of diabetes.

“We are treating the complications of diabetes such as late stage renal failure, painful neuropathy and vision loss,” Gardner says. “Our goal is to make this obsolete – to find ways so that patients can retain kidney function, integrity of nerves and keep their vision – in spite of diabetes.”

Additional investigators in the metabolic reprogramming study include Steven Abcouwer, Ph.D., David A. Antonetti, Ph.D., Hosagrahar V. Jagadish, Ph.D., Matthias Kretzler, M.D., David Lombard, M.D., Ph.D., Rodica Pop-Busui,M.D., Ph.D.; Nathan Qi, Ph.D., and Kerby Shedden,Ph.D.

The U-M study will use the infrastructure of the Michigan Metabolomics and Obesity Center. This center has developed technology for assessing the utilization of different metabolites by tissues in animals and in humans which may be the basis for the development of complications of diabetes.

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Source: University of Michigan Health System