DISCUSSION
The main finding of our study; PWD and atrial conduction and EMD times
were significantly higher in the GDM group than otherwise healthy
pregnant women. Additionally, positive significant correlation was found
between intraatrial EMD and PWD.
GDM is observed in approximately 7 % of all pregnancies16. In most affected women, blood glucose returns to
normal levels in the postpartum period. However, there is a wealth of
evidence for the development of DM later in life in women with a history
of GDM 17,18. However, whether there is a relationship
between GDM and cardiovascular diseases is still a research topic. GDM
has also been associated with cardiovascular diseases19. DM is associated with increased AF
risk20. Whether GDM may predispose to increased AF
risk at long-term is not known. For this reason, in our study, we
searched PWD and atrial EMDs, which may be early predictors of future AF
risk, in patients with GDM.
Since PWD is a non-invasive simple method, its relationship with atrial
arrhythmias in both cardiovascular and other diseases has been widely
investigated. Among the subjects of these studies are type II diabetes21, pre-diabetes22,
hypertension11, hyperthyroidism23,
rheumatoid arthritis 24, systemic lupus erythematosus25, ankylosing spondylitis 26,
familial Mediterranean fever27 , scleroderma28, obesity29 , inflammatory bowel
disease30, metabolic syndrome 31,
obstructive sleep apnea syndrome 32, and hemodialysis33. Susceptibility to atrial arrhythmias increases in
all these diseases and it has been found that PWD is prolonged in these
situations. To our knowledge, PWD and atrial conduction time have not
been investigated in in GDM patients. Clinical value of our finding of
increased PWD in GDM patients in the present study requires long-term
follow-up.
Several studies have been conducted in patients with type II DM using
similar methods with our study. Akyel et al., 40 patients with type II
DM and 40 members of the control group were evaluated, and PA mitral and
PA septal times were found to be higher in the diabetic group34. Demir et al. evaluated 88 type II DM patients and
49 age- and sex-matched controls. They reported that PWD was higher in
DM patients than in the controls. Moreover, they found that interatrial,
intraatrial, and intraleft atrial EMDs were higher in type II DM
patients, and they observed a positive correlation between inter-atrial
EMD and PWD 21. Our findings are in accordance with
those reports.
PWD reflects heterogeneous atrial conduction with the detection of
abnormal atrial conduction in different ECG leads. The mechanism
underlying the increase in PWD in diabetic patients is not clearly
known, but the structural and electrophysiological changes caused by
diabetes in the atrium are thought to play an important role. Chronic
hyperglycemia causes structural and functional disorders by changing the
chemical structure of the proteins in the cell membrane. In addition,
interstitial fibrosis of the myocardium and extracellular protein
deposition cause variability in atrial conduction velocity and atrial
refractoriness, resulting in an increase in PWD. Therefore, it is
suggested that PWD can be used in the diagnosis of high-risk patients
for AF 21,31,35,36.
Similar results have been reported in animal studies. Fu et al. found
that atrial electromechanical properties were significantly impaired in
diabetic rabbits 37. Kato et al. reported that
intra-atrial activation time and atrial fibrotic storage increased in
diabetic animal models 38. Watanabe et al. evaluated
the hearts of diabetic rats with the optical mapping method and stated
that the atrial conduction velocity slowed 39. In an
animal study conducted by Li et al. in 2016, the relationship between DM
and the P wave was examined at the molecular level. The researchers
found that longer P-wave duration in rats with type II DM was not
dependent on left atrial enlargement. Rather, it was associated with
fibrosis and expression of gap junction proteins such as Cx40 and Cx43,
which are important for the progression of impulses in the heart40. The increase in PWD, which is one of the main
findings of our study, may be due to changes at the cellular level.
PWD and atrial EMD have also been reported in patients with
pre-diabetes. Mahfouz et al. stated that as well as PA lateral, PA
septal, and PA tricuspid durations, intra-atrial and inter-atrial EMDs
were higher in pre-diabetic patients 41. It was
suggested that, atrial cell damage starting in the pre-diabetic phase
which includes alterations in the chemical composition of proteins such
as collagen I and elastin, may result in changes in atrial conduction
times 42. The physio pathological mechanisms
underlying PWD and prolonged atrial conduction times may be similar in
GDM patients.
This was a small numbered, cross-sectional, single-center study.
Long-term follow up to observe prospective atrial arrhythmic events is
lacking. Another limitation of our study was that body mass indexes were
not equal in the two groups. However, higher BMI itself is associated
with GDM and is a risk factor for GDM. Although there was no significant
difference in diastolic BP between GDM and control groups, it was not
similar in terms of systolic BP. Nevertheless, all the patients had
normal blood pressures. Manual calculation of ECG P-wave durations and
PWD is another limitation. Atrial conduction times were measured by
tissue Doppler echocardiography, not by the invasive
electrophysiological study which is the gold standard.