Complications of Type 1 Diabetes

This DBP collaboration is establishing interactions among the University of Michigan Juvenile Diabetes Research Foundation (JDRF) Center, the Brehm Center for Type 1 Diabetes Research and Analysis, and the National Center for Integrative Biomedical Informatics (NCIBI).  Such a long-term relationship will create new research initiatives in type 1 diabetes, develop models for biological processes relevant to research on the complications of type 1 diabetes, and be sustained through future funding.

Overall Goals

1. To characterize the anti-oxidant response in diabetes and generate therapeutic targets and effective experimental therapies
2. To apply a systems approach to multi-level analyses of complications affecting nerves and kidneys.

Specific Aims

In Neuropathy:

1. To characterize the anti-oxidant response in diabetes and explore effects on new therapeutic targets of thiazolidinediones (TZDs), specifically Rosiglitazone (RGZ). 
   
2. To identify the genes activated by oxidative stress and analyze the list for common functions and regulatory regions using JUMiner, a web-based literature mining and functional analysis tool.
In Nephropathy:
3. To identify molecular signatures and mechanisms in diabetic nephropathy that would help define the disease process active in individual patients ("personalized medicine") and compare those findings with similar phenotypes of chronic kidney failure from other causes.
For both Type 1 and Type 2:
4. Utilize a "systems" approach to diabetes by merging data from genetic variation, transcriptional regulation, molecular interactions, metabolic profiles, endocrinology and clinical phenotypes of patients.
   
5. Develop a metabolome ontology and use advanced metabolite patterns as biomarkers for disease state, progression and treatment outcome.

Related Publications

Wiggin TD, Kretzler M, Pennathur S, Sullivan KA, Brosius FC, Feldman EL. Rosiglitazone treatment reduces diabetic neuropathy in streptozotocin-treated DBA/2J mice. Endocrinology 2008; 149(10): 4928-37. PMID: 18583417.

Sullivan KA, Hayes JM, Wiggin TD, Backus C, Su Oh S, Lentz SI, Brosius F, Feldman EL. Mouse models of diabetic neuropathy. Neurobiol Dis 2007; 28(3): 276-85. PMID: 17804249.