Michael Mauer, Principal Investigator

Microarray Studies of Skin Fibroblasts in Type 1 Diabetes

Diabetic nephtopathy (DN) is the leading cause of kidney failure and was responsible for 44% of all the new cases of kidney failure in the U.S. in 2001. These researchers are studying cultured skin fibroblast (SF) and renal proximal tubal epithelial cells (PTEC) from type 1 diabetic patients in order to better understand the differences in behavior of these in patients with and without DN. They are testing the hypothesis that there are inherent cellular differences between type 1 diabetic patients with or without DN, and that these differences are genetically determined and are associated with altered SF and/or PTEC gene expression.

There is accumulating evidence that genetic factors not associated with the risk of type 1 diabetes convey risk or protection from DN. The evidence is originally derived from the observation of familial clustering of DN risk. Type 1 diabetic siblings of DN patients have a five-fold higher prevalence of DN than do type 1 siblings of patients without DN. Studies also demonstrate concordance for the severity and patterns of glomerular lesions in type 1 sibling pairs, even after factoring for metabolic control, duration of diabetes, and other factors. However, the genes that may be involved in the pathogenesis of DN are unknown. Several research groups are exploring the specific genes responsible for the onset or progression of DN, but the single candidate gene has approach has been inconclusive. One approach is to study cells in vitro, which, after several passages in tissue cultures, can be assumed to better reflect intrinsic rather than environmental factors. The goal of these researchers is to use microarray techniques to test for gene expression differences in total ribonucleic acid isolated from SF and PTEC from type 1 diabetic patients that have been structurally and functionally polarized into two groups: one a “fasttrack” group (high risk of DN) and one a “slowtrack” group (low risk of DN).