Effect of Elevated Plasma-Free-Fatty-Acids on Renal Hemodynamic Parameters

Summary

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.

Conditions

• Renal Circulation
• Renal Plasma Flow
• Glomerular Filtration Rate
• Fatty Acids, Nonesterified

Interventions

DRUG

NG-monomethyl-L-Arginine (L-NMMA)

DRUG

triglycerides (Intralipid 20%)

DRUG

heparin

DRUG

somatostatin

DRUG

insulin

DRUG

glucose

DRUG

inulin

DRUG

paraamino hippurate (PAH)

Sponsors & Collaborators

• Medical University of Vienna

  lead OTHER

Principal Investigators

• Michael Roden, MD · Department of Internal Medicine III, Medical University of Vienna

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

19 Years

Max Age

35 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

1999-07-31

Completion

2000-06-30

Countries

• Austria

Study Locations