News & Research

    University of Pittsburgh, Pittsburgh, Pennsylvania

Evaluation of skeletal muscle oxidative metabolism in type II diabetes by quantitative

General Research Subject: Type 2 Diabetes

Focus: Exercise, Exercise\Regulation of Muscle Metabolism, Foot Care, Foot Care\Lower Extremities, Integrated Physiology\Muscle, Metabolism

Type of Grant: Innovation

Project Start Date: July 1, 2012

Project End Date: June 30, 2014

Research Description

Abnormal skeletal muscle energetics and oxygen kinetics in type II diabetes mellitus (DM) contribute to skeletal muscle microvascular and mitochondrial dysfunction, which is often responsible for the exercise intolerance and the development of foot ulceration in diabetic patient that eventually leads to more than 80,000 lower extremity amputations per year. Currently, there are no clinically-ready techniques to evaluate the progression of diabetic lower extremity disease and the outcome of various therapeutic interventions. Magnetic Resonance Imaging (MRI) is the preferred imaging modality since it can provide comprehensive information about the structural, vascular, and metabolic function of skeletal muscle.

Currently there are no techniques of quantifying muscle oxidative metabolism can resolve spatial and functional heterogeneities among different specific muscle groups, especially the regulation of oxidative metabolism at the onset of exercise and during recovery. The proposed novel, non-invasive MRI-based approach allows evaluation of regional muscle oxidative metabolism pertaining to DM, and can be used to sensitively and reliably track and quantify the regional muscle oxygenation of the lower extremity at the mid-calf level. It is anticipated that after comprehensive optimization and validation, the proposed new diagnostic tool will pave the way to new therapeutic strategies that will greatly enhance the efficacy, efficiency and cost-effectiveness in managing DM.  In addition, this will also contribute to broadening our knowledge on physiopathology of other MSK diseases such as diabetic nephropathy, soft tissue tumor, mitochondrial myopathy, muscle fatigue syndrome, aging related muscle metabolism disorder, and Duchenne muscular dystrophy.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating
and/or curing diabetes?

Abnormal skeletal muscle energetics and oxygen kinetics in type II diabetes mellitus (DM) contribute to skeletal muscle microvascular and mitochondrial dysfunction, which is often responsible for the exercise intolerance and the development of foot ulceration in diabetic patient that eventually leads to more than 80,000 lower extremity amputations per year. Currently, there are no clinically-ready techniques to evaluate the progression of diabetic lower extremity disease and the outcome of various therapeutic interventions. Magnetic Resonance Imaging (MRI) is the preferred imaging modality since it can provide comprehensive information about the structural, vascular, and metabolic function of skeletal muscle.

Currently there are no techniques of quantifying muscle oxidative metabolism can resolve spatial and functional heterogeneities among different specific muscle groups, especially the regulation of oxidative metabolism at the onset of exercise and during recovery. This research proposed a novel, non-invasive MRI-based approach which allows evaluation of regional muscle oxidative metabolism pertaining to DM, and can be used to sensitively and reliably track and quantify the regional muscle oxygenation of the lower extremity at the mid-calf level. It is anticipated that after comprehensive optimization and validation, the proposed new diagnostic tool will pave the way to new therapeutic strategies that will greatly enhance the efficacy, efficiency and cost-effectiveness in managing DM. In addition, this will also contribute to broadening our knowledge on physiopathology of other MSK diseases such as diabetic nephropathy, soft tissue tumor, mitochondrial myopathy, muscle fatigue syndrome, aging related muscle metabolism disorder, and Duchenne muscular dystrophy.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

Our research team has been focused on the MRI-based non-invasive mapping of skeletal muscle oxygen metabolism in diabetes patient. Abnormalities of skeletal microvascular and mitochondrial induced by diabetes mellitus is often responsible for the development of foot ulceration which eventually leads to lower extremity amputations. With the success of our proposed research, in combination with existing MRI techniques that provide high quality anatomic, blood perfusion, muscle pH value and energetics images, our approach will empower a more comprehensive and integrated approach to investigate the impact of diabetes in the lower extremity muscle function.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your
research efforts?

My motivation to start research in diabetes involves my personally experienced on the impact of diabetes to family members. My father-in-law has been diagnosed with type II diabetes almost twenty years ago at the age of 55. While the progression of disease has been well-controlled by the combination of rigorous dietary management and medicine to control blood glucose and blood pressure, he starts developing eye complications in recent years and one of his eye becomes almost blind.

I have just started my independent research two years ago at the Department of Radiology, University of Pittsburgh. As an MRI physicist, my main research focus is non-invasive quantification of organ oxygen metabolism. This Innovation Award from ADA gives me an opportunity to apply my experience to study the effect of diabetes mellitus on the dynamics of skeletal muscle oxygen delivery/utilization after exercise. It is wide know that muscle has significant functional heterogeneities, thus this MRI-based imaging approach can provide more insights on the physiopathology of DM.

In what direction do you see the future of diabetes research going?

While researches on the diabetes biology are crucial for the searching of a cure, early diagnosis and proper management of diabetes-related complications are important to improve the life quality of diabetic patients. I believe that radiology, especially MRI, can provide a significant tool to aid the diabetes research. With recent advances on MRI-based quantification of disease-related effect on nephropathy, skeletal muscle function, peripheral arterial disease (PAD) and foot complications, MR imaging becomes an comprehensive and integrated approach for diabetes research.