The goals of this project are to discover metabolomic biomarkers for diabetic nephropathy (DN) in type 1 diabetes mellitus (T1D) patients and to understand the pathophysiology of DN. The study hypotheses are: . 1. There are biochemical changes in the plasma and urine of T1D patients with incipient DN that will manifest before the onset of microalbuminuria; and 2. There are biochemical signatures that indicate which T1D patients are most likely to develop diabetic nephropathy (DN), and therefore who will most benefit from preventative measures. To test these hypotheses, we aim to: 1. Establish methods of sample preparation for metabolic profiling in patients with T1D. We will develop procedures for processing urine samples, as well as optimize current procedures for processing plasma to derive separate fractions suitable for metabolomic and proteomic analysis from the same samples. Five pairs of samples will be used; 2. Assemble a specimen bank for metabolomic and subsequent proteomic analysis of plasma and urine samples from: a. 30 recently diagnosed pre-nephropathic T1D patients, b. 30 pre-nephropathic patients with T1D for five to ten years, c. 30 patients with early nephropathy (microalbuminuria), and d. 30 patients with T1D over twenty years, but no evidence of DN. Patients will not be on antihypertensive medications. 3. Identify metabolic signatures that correlate with the progression of DN by comparing samples from patient groups a, b, and c. 4. Identify metabolic signatures that predict the likelihood of developing DN by comparing samples from patient groups b, c and d. In this manner, we hone to identify potential metabolomic biomarkers worthy of subsequent validation.
