1- Microvascular Function Clinical Trial
Official title:
Acute and Short-term Chronic Effects of Galvus (Vildagliptin) on Endothelial Function and Oxidative Stress on Recently Diagnosed Type 2 Diabetic Obese Women: the Role of Intestinal Peptides During Lipid Overload
The prevalence of obesity and type 2 diabetes mellitus (T2DM) has increased progressively in
the past decades, and consequently, a higher incidence of cardiovascular diseases is
observed. As this process develops, the endothelial dysfunction is present at early stages
of the atherosclerotic disease. Studies conducted at BioVasc/UERJ show the occurrence of
endothelial and microvascular dysfunction in obese carriers, even in the absence of
dysglycemia. New concepts indicate the endothelium as a possible therapeutic target, and
drugs which act not only on diabetes mellitus pathophysiology but also acting as direct
cardiovascular protectors bring new therapeutic possibilities. The dipeptidyl-peptidase-4
inhibitors (DPP4), such as vildagliptin, are drugs used on the T2DM treatment. Its incretin
mimetic and insulinotropic effects are already well established and several other studies
show its effectiveness in reducing glycated hemoglobin, even in monotherapy.
Currently, fat rich foods are being increasingly introduced in the western way of life and
recent evidence suggests that the postprandial lipemia (LPP) is related to cardiovascular
risk. A better glucose control using vildagliptin can reduce the oxidative stress, and
consequently promote a better microvascular and endothelial reactivity. However,
vildagliptin can have an additional cardiovascular protective action, not only because of
its effect on glycemia and oxidative stress reduction, but maybe because of its direct
effect on intestinal peptides with postprandial lipemia reduction. To test this hypothesis,
we will proceed the following exams: venous occlusion pletysmography, nailfold
videocapilaroscopy and laser-Doppler flowmetry aiming to evaluate vascular reactivity on
muscle and at cutaneous site. Anoter group of patients with the same clinical
charactherisitics will use metformin, in order to compare its effects with those obtained
from the use of Vildaglitpin. Our purpose is to determine whether vildagliptin, evaluated in
obese and diabetic women, has vascular protective effects, and whether the regulatory
mechanisms of these actions correlate with oxidative stress, inflammatory markers and
intestinal peptides in baseline state and after a lipid overload.
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