Diabetic Nephropathies Clinical Trial
Official title:
Role of NO Activity for the Development of Diabetic Nephropathy
Experimental data suggest that oxidative stress and endothelial dysfunction are key players
in the pathogenesis of diabetic nephropathy. In the last few years the investigators were
able to establish a method to assess endothelial function of the renal vasculature in humans
and started to systematically study a variety of cardiovascular disorders known to be
associated with endothelial dysfunction in other vascular beds, including hypertension,
hypercholesterolemia and type-2 diabetes. In patients with type-2 diabetes the investigators
could demonstrate that despite unaltered basal and stimulated NO-activity, the renal
response to the antioxidant vitamin C was more pronounced compared to control subjects.
These data suggest that oxidative stress is increased in the renal vasculature of diabetic
patients. Furthermore, NO-activity in diabetic patients appears to be upregulated to
compensate for the increase in oxidative stress. This hypothesis is supported by the
demonstration of increased endothelial nitric oxide synthase (eNOS) expression in kidney
biopsies of diabetic patients.
The major focus of the investigators' current research activities is to assess the role of
endothelial dysfunction in the very early stages of diabetic nephropathy. To this end,
patients with increased fasting glucose or metabolic syndrome will be studied in comparison
with an age-matched control group. Endothelial function and the role of oxidative stress
will be assessed in the renal vasculature in all groups. In parallel, the investigators will
study endothelial function in the forearm by venous occlusion plethysmography and in the
retinal vasculature by scanning laser doppler flowmetry to dissect regional differences in
the regulation of endothelial function. Further aspects include the role of
microalbuminuria, glomerular hyperfiltration, and endogenous inhibitors of NO synthase such
as NG,NG-Dimethyl-L-Arginine (ADMA). In a therapeutic approach, the investigators will
determine the effects of various antioxidant treatment strategies on endothelial function
and their potential role in the prevention of diabetic nephropathy.
n/a
Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
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