Background
Cardiovascular disease is the main cause of mortality
among people with type 2 diabetes mellitus (T2DM)
[1,2]. Accelerated atherosclerosis in these patients is
preceded by endothelial dysfunction, inflammatory
burden, and increased lipid peroxidation, all leading to
enhanced macrophage foam cell formation [2]. In
addition to the average blood glucose concentration,
acute glycemic fluctuations from peaks to nadirs (glucose
variability) may be involved in the development of
diabetic complications [3], as they contribute to the
generation of excessive protein glycation and oxidative
stress [4]. High glucose variability has been shown to be
associated with endothelial dysfunction in patients with
T2DM and optimal metabolic control [5]. Currently, the
mean amplitude of glycemic excursion (MAGE) is one
of the most used methods for detecting significant
swings in glycemia [6], but other tools may be useful to
identify disturbances in glucose variability [7].
Some current treatments for T2DM have already been
tested concerning their possible effects in reducing glucose
variability as well as reducing glycated hemoglobin
(HbA1c) [8]. Exercise, which is one of the cornerstones
of treatment for hyperglycemia in T2DM because of its
beneficial effect on HbA1c [9], was recently shown to
reduce glucose variability in addition to its acute effects
on reducing glucose levels [7]. Vildagliptin and sitagliptin
are two drugs that were recently evaluated in a study
focusing on possible differences in daily glucose fluctuations
in patients with T2DM inadequately controlled
with metformin, and it showed that vildagliptin was more effective in flattening acute glucose fluctuations
over a day [8]. Moreover, acarbose was superior to glibenclamide
in reducing MAGE. Therefore, aside from
their absolute glucose-lowering effect, it is evident that
other effects of different anti-diabetic agents might also
be different [10].
The present study will be conducted to test the hypothesis
that in combination with metformin, vildagliptin may
produce a greater improvement in glucose variability after
a submaximal exercise test, compared with glibenclamide.
Our general aim will be to evaluate glucose variability
after the submaximal exercise test in patients receiving
treatment with vildagliptin or glibenclamide. The specific
aims of this study are to evaluate the oxidative stress,
endothelial function, and metabolic and cardiovascular responses
to exercise in patients treated with vildagliptin or
glibenclamide.