UTHSC researchers receive $1.99 million to advance understanding of diabetes pathophysiology

The National Institute of Diabetes and Digestive and Kidney Diseases recently awarded a team of UTHSC researchers $1.99 million for their work to advance understanding of the pathophysiology of prediabetes, diabetes, and related complications. Sam Dagogo-Jack, MD, professor of Medicine and director of the General Clinical Research Center, is a principal investigator, along with Nawajes Mandal, PhD, associate professor in the Departments of Ophthalmology, Anatomy and Neurobiology, and Pharmaceutical Sciences. Their project is titled "Ceramides and Sphingolipids as Predictors of Incident Dysglycemia."

Dr. Dagogo-Jack is a leading clinical researcher and an expert on diabetes and prediabetes. Dr. Mandal is a basic scientist and a leading expert on the role of bioactive lipid signlaing, like sphingolipids (SPLs) and ceramides, in human ocular, metabolic, neurodegeneration, and inflammatory diseases. Using their combined expert perspectives, the two hypothesize that ceramides and other SPLs are critical modulators affecting the progression from normal glucose regulation, through prediabetes, to type 2 diabetes and associated diabetic complications.

To test this hypothesis, they will utilize specimens from two studies in which Dr. Dagogo-Jack is the principal investigator: the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC), which involved participants with a normal concentration of glucose who had a parental history of type 2 diabetes; and the Diabetes Prevention Program/Diabetes Prevention Program Outcome Study (DPP/DPPOS), which followed participants already diagnosed with prediabetes for the development of type 2 diabetes. Additionally, samples from 200 individuals with normal glucose concentrations and no family history of diabetes will serve as normative controls.

The project will analyze, profile, and compare samples at baseline against various follow-up intervals to investigate several aims. Drs. Dagogo-Jack and Mandal hope to determine the role ceramide and SPLs play in prediabetes risk among people with normal glucose and a family history of type 2 diabetes, in preventive treatments for type 2 diabetes, and in the development of diabetic complications, particularly vascular disease. The project includes planned lipidomics analyses to find new predictive, prognostic and specific biomarkers for prediabetes, type 2 diabetes, and vascular complications.

I am delighted that my colleague, Dr. Mandal, and I were able to pool our expertise to launch this collaborative study. The award from the NIH not only endorses the scientific merits of our proposal, but also gives a nod to the idea of interdisciplinary collaborative research between clinical and basic science investigators."

Dr. Dagogo-Jack, Director, UTHSC Division of Endocrinology, Diabetes and Metabolism

"The scope of the sphingolipid system's impact on mammalian biology has proven to be impressive, and its roles in human diseases associated with inflammation, neovascularization, tumorigenesis, and diabetes is only beginning to be understood," said Dr. Mandal. "Our planned comprehensive analysis of ceramide regulation across the glycemic spectrum from normoglycemia through prediabetes to type 2 diabetes will unravel specific roles of ceramides and other SPLs in the pathogenesis and will provide novel SPL-related biomarkers predictive of the development and progression diabetes and its complications."

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