Response to Comment on: Rizzo et al. Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes: Role of Dipeptidyl Peptidase-IV Inhibition. Diabetes Care 2012;35:2076–2082
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D and sitagliptin groups reported
difeVries (1) was surprised that vildagliptin
ferent mean amplitude of glycemic
excursions (MAGE) reduction because
they have similar fasting and postprandial
glucose levels and suggested reporting other
measures of glucose variability to better
understand these results.
Indeed, a previous study evaluating
the role of glycemic variability in type 2
diabetic patients has demonstrated that
patients with similar mean glucose and
postprandial glucose have a markedly
different daily glucose profile with
differences both in number and duration of
excursions (2). The difference in MAGE
reduction found in the two study groups
may be better clarified by the different
glucagon-like peptide 1 (GLP-1) daily
profiles of the two drugs (3) rather than
by a graph showing changes in mean
glucose values. In such GLP-1 profile,
vildagliptin group had higher plasma
GLP-1 levels not only during postprandial
but also during interprandial periods.
The main aim of our study was to
evaluate the effects of blunted glucose
excursions on oxidative stress and
inflammation parameters, which have
previously been found associated with daily
glucose fluctuations (4). Many different
indexes have been proposed to assess
glucose variability, but at the moment no
gold standard procedure is available
(5). Despite the fact that MAGE displays
some significant limitations, it is the most
common measure used for evaluating the
association between glycemic variability
and oxidative stress and inflammation
parameters (4) and is the most appropriate
to detect large glycemic peaks and nadirs
encountered during a day (5), whereas
continuous overlapping net glycemic
action (defined as the SD of the differences
between the current observation and the
previous 2-h observation) is known to
detect small glycemic swings and more
appropriately describes the glycemic
fluctuation of patients in optimal metabolic
balance, without peak and nadir related
to hypoglycemic treatment. In addition,
SD, which is considered to be the simplest
tool for describing glycemic variability
that takes into account all excursions,
has the limit of including all oscillations
without a weighting of the minor or major
variations (5). Several other methods such
as mean absolute glucose change have been
proposed but have not gained widespread
use. We acknowledge that the different
indexes do not seem to be interchangeable
and should be used in the appropriate
condition; indeed, most of these indexes
are highly correlated (4) and provide the
same information, making reasonable a
reduction in the number of indexes that
need to be considered. Whether calculating
MAGE, SD, mean absolute glucose change,
continuous overlapping net glycemic
action, or other measures simultaneously
helps to get additional insight in
pathophysiological processes needs further
investigation (4,5).
MARIA ROSARIA RIZZO, MD, PHD
MICHELANGELA BARBIERI, MD, PHD
c c c c c c c c c c c c c c c c c c c c c c c c
References
1. DeVries JH. Comment on: Rizzo et al.
Reduction of oxidative stress and
inflammation by blunting daily acute glucose
fluctuations in patients with type 2 diabetes:
role of dipeptidyl peptidase-4 inhibition.
Diabetes Care 2012;35:20762082
(Letter). Diabetes Care 2013;36:e12. DOI:
10.2337/dc12-1218
2. Ceriello A, Esposito K, Piconi L, et al. Os
cillating glucose is more deleterious to
endothelial function and oxidative stress than
mean glucose in normal and type 2 diabetic
patients. Diabetes 2008;57:13491354
3. Rizzo MR, Barbieri M, Marfella R, Paolisso
G. Reduction of oxidative stress and
inflammation by blunting daily acute
glucose fluctuations in patients with type 2
diabetes: role of dipeptidyl peptidase-IV
inhibition. Diabetes Care 2012;35:2076
2082
4. Monnier L, Mas E, Ginet C, Michel F, Villon
L, Cristol JP, et al. Activation of oxidative
stress by acute glucose fluctuations
compared with sustained chronic
hyperglycemia in patients with type 2 diabetes.
JAMA 2006;295:16811687
5. Hill NR, Oliver NS, Choudhary P, Levy JC,
Hindmarsh P, Matthews DR. Normal
reference range for mean tissue glucose and
glycemic variability derived from
continuous glucose monitoring for subjects
without diabetes in different ethnic
groups. Diabetes Technol Ther 2011;13:
921928