Effect of Elevated Plasma-Free-Fatty-Acids on Renal Hemodynamic Parameters
Type 2 diabetes is frequently associated with elevation of plasma-free fatty acids (FFA). Studies indicate that elevation of plasma-FFA induces insulin resistance and also causes endothelial dysfunction as well as hemodynamic changes which are supposed to be involved in the pathogenesis of diabetic vascular disorders.
Glomerular hyperfiltration, which is associated with glomerular hypertension and hypertrophy, a common finding in the early course of type 1 diabetes as well as type 2 diabetes, plays an important role in the development and progression of diabetic nephropathy. These hemodynamic changes are not well understood, but are most likely induced by dilatation of the (precapillary) glomerular arteriole.
In humans the hemodynamic effect of FFAs has so far been investigated locally in brachial and femoral arteries and recently in the eye and skin, where FFAs induced a pronounced increase in blood flow probably due to a local decrease in vascular resistance.
The aim of the present study is to characterise the hemodynamic effects of FFAs in the kidney. In addition we want to test the hypothesis that FFA-induced changes are mediated via endothelial derived nitric oxide (NO). The results of this study could provide information to what extent elevated FFA-plasma levels contribute to hyperfiltration in the early course of diabetes mellitus. The measurements will be done at baseline and during 4 hour infusion of a triglyceride or placebo infusion, combined with heparin.
Renal Plasma Flow
Glomerular Filtration Rate
Fatty Acids, Nonesterified
Drug: NG-monomethyl-L-Arginine (L-NMMA)
Drug: triglycerides (Intralipid 20%)
Drug: paraamino hippurate (PAH)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
|Official Title:||Effect of Elevated Plasma-Free-Fatty-Acids on Renal Hemodynamic Parameters|
|Department of Clinical Pharmacology, Medical University of Vienna|
|Vienna, Austria, 1090|
|Principal Investigator:||Michael Roden, MD||Department of Internal Medicine III, Medical University of Vienna|