This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.In subjects with diabetes microalbuminuria predicts both end-stage renal disease and clinically significant cardiovascular disease. Despite decreases in renal and cardiovascular complication rates over the past few decades, a significant number of patients still progress to endstage renal disease and diabetic nephropathy is the leading cause of endstage renal disease. Cardiovascular disease is the leading cause of death in these patients and the risk begins to accelerate with microalbuminuria. Some studies have shown that nephropahty, insulin resistance, increase weight-hip ratio, and corornary artery disease track through the families of subjects with type I diabetes and nephropathy. In studies of subjects without type I diabetes, central obesity confers increased risk of cardiovascualr disease and elevates AER.This proposal will evaluate the role of IAF mass in the development of elevated albumin excretion and dyslipidemia in subjects with type I diabetes. A better understanding of mechanisms which underlie the relationship between central obesity and the earliest stages of DN may lead to improved outcomes in renal and cardiovascular disease. The insights gained from this work may lead to improved, individualized therapy in type I diabetes. These studies are being done in a group of very well-characterized subjects with type I diabetes, some of whom exhibit a specific phenotype shared by many type 2 patients (tendency to weight gain with intensive therapy and increased IAF). The answers obtained will be applicable to some subjects with type 2 disease, particularly Native American and Hispanic populations which have a high prevelence of central obesity.GCRC support request: This project will be centered at the University of Minnesota, but will also involve the University of Washington, the Mayo Clinic, and the International Diabetes Center in Minneapolis, Minnesota. Subjects recruited for participation in the cross-sectional study of the 3 Minnesota EDIC cohorts will be seen at the University of Minnesota GCRC or at their usual site (Univ. of MN, International Diabetes Center, or Mayo Clinic), based on subject preference and available facilities, for their regularly scheduled EDIC study visit. All subjects recruited for the weight loss intervention will be seen at the U of MN GCRC. The GCRC metabolic kitchen, research dietitians, and nursing staff will all be utilized for this study. A control population without diabetes will provide comparative data.
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