Chronic hyperglycemia in patients with type II diabetes can lead to a variety of complications including nephropathy and retinopathy. One of the major pathophysiological mechanisms by which hyperglycemia may lead to characteristic irreversible tissue damage is the formation of glucose-derived cross links in proteins (advanced glycated endproducts [AGE's]) that result in increased stiffness, abnormal protein accumulation, membrane leakiness and dysfunction. Patients with diabetes have been shown to have higher levels of serum AGE's than nondiabetic subjects, and the AGE levels are proportional to the severity of diabetic nephropathy. Also, reactive intermediates formed during periods of hyperglycemia may continue to cross-link with proteins even after blood glucose is lowered. Therefore, normalization of blood glucose may not completely prevent the progression of complications, and a pharmacologic agent, such as pimagedine, may be of significant benefit in the treatment of such patients. This multicenter study will evaluate the effect of pimagedine therapy on patients with NIDDM who have evidence of nephropathy, ranging from microalbuminuria with essentially normal renal function to frank renal impairment. Patients will be followed for up to four years. We have only recently initiated this study, which is anticipated to last 2 - 4 years, at Duke, and thus have no data available as yet. We intend to enroll 15 patients.
Showing the most recent 10 out of 128 publications
