Discussion:

To the best of our understanding, this study serves as the first comprehensive report on the
nationwide prevalence, risk factors, neonatal outcomes, and maternal outcomes associated with
gestational diabetes mellitus (GDM) specifically in Dhaka, Bangladesh.

A. Prevalence
In our study, clinical data from 5096 Bangladeshi pregnant women from three hospitals at Dhaka
city in Bangladesh were retrospectively analyzed. The study enrolled 800 subjects, with 62%
(n=500) identified as gestational diabetes mellitus (GDM) patients and 38% (n=300) as non-
GDM. Among 5096 pregnant women, the Glucose Challenge Test (GCT) yielded positive results
in 58% (n=3000) cases. Subsequently, the Oral Glucose Tolerance Test (OGTT) was
administered (second trimester 13–24 weeks) to the 3000 GCT-positive pregnant women,
utilizing a 140 mg/dl cutoff point. Our study of 500 pregnant women suggests that using a cut-off
value for HbA1c (Glycosylated hemoglobin) at 6.1% and OGTT could be a useful screening tool
for GDM. The major effect on HbA1c is usually seen in the last 4–8 weeks of red cell age. Thus,
it should be interpreted with caution if detecting a new diagnosis of GDM [1a]. Based on the
results, 500 individuals were diagnosed with GDM, resulting in a prevalence of Dhaka city 16%
(500/3000). The results revealed a GDM (Gestational Diabetes Mellitus) incidence of Dhaka
city was 17%. The prevalence in this study exceeded the combined GDM prevalence of 11.4%
reported in South Asian countries (Bangladesh, India, and Sri Lanka) [8]. The overall prevalence
of GDM in Bangladesh was 35% (95/272) [1].

Base line

B. Risk factors
Maternal age, BMI, parity, previous history of gestational diabetes and family history of
diabetes are the high risk factors of GDM Socioeconomic status does not affect the prevalence of
GDM.[ [5]. The incidence of GDM appeared to increase steadily with age in all pre-pregnancy
BMI groups (all P < 0.05). Older age (≥30 years), gestational BMI gain from pre-pregnancy to
15–20 weeks of gestation, history of GDM and thyroid diseases were risk factors for GDM.
There were significant interactions between pre-pregnancy BMI and age.[6]

This study was conducted to clarify the importance of risk factors for GDM in a study of 500
women with GDM and 300 healthy women. Logistic regression analysis was employed to
investigate the risk factors associated with GDM. The findings indicated that advanced maternal
age, who are housewives, more than 3 parities, pregnancy BMI overweight, a history of diabetes
mellitus in first-degree relatives, a history of abortion, and a positive status for thyroid
peroxidase antibodies (TPOAb (+)) were all linked to an increased risk of GDM. These results
suggest that GDM is prevalent in the specified Dhaka city in Bangladesh and is influenced by a
many risk factors.
Age and GDM

Seshiah et al. found the highest gestational diabetes mellitus (GDM) prevalence in the 30-34 age
groups [2]. Other studies also noted significant age differences (<25, ≥25 years) [3]. Zargar et al.
reported a rising GDM prevalence with age (1.7% in <25 years to 18% in ≥35 years) [4]. In our
study, the peak prevalence was in 30-34 years, but the women’s age in years (<25 and ≥25)
based on the median age of the study population was more significant. In the multivariate
adjusted model, advanced age and urban residence showed a significant association with GDM
(Table 6). Women aged 25 years and above were thirteen times (aOR 13.69, 95% CI 9.620–
19.25) more likely to have GDM compared to the women aged below 25 years.

BMI and GDM Mean age ≥25 was a GDM risk factor, possibly due to age-related declines in (1)
islet cell mitochondria's oxidative phosphorylation weakening insulin function; (2) insulin-
mediated glucose uptake ability; and (3) increased mental stress in older pregnant women,
causing anxiety and elevated blood glucose. Long-term anxiety could activate the sympathetic
nerve, raising blood glucose via the hypothalamic–pituitary–adrenal axis.

BMI and GDM

BMI is a common obesity indicator, closely linked to Gestational Diabetes Mellitus (GDM) [18].
Pregnant women who are overweight or obese are more likely to develop GDM due to
heightened insulin resistance. Pre-pregnancy BMI is also associated with rs2021966 ENPP1
polymorphism, with A allele homozygosity increasing the risk of impaired glucose tolerance and
GDM [19]. Low pre-pregnancy BMI and minimal gestational weight gain are associated with
increased risks of small-for-gestational-age births, preterm births, and low birth weights [20, 21].
Additionally, evidence suggests a link between low pre-pregnancy BMI and infertility [22]. We
observed a higher incidence of GDM in women with an excessive gestational BMI gain during
the early stages of gestation. In this study, GDM group pre-pregnancy BMI was higher than in
the non-GDM group, with a 0.22-fold increased risk of GDM.

History of diabetes mellitus in first-degree relatives and GDM

Similar to Type 2 Diabetes Mellitus (T2DM), Gestational Diabetes Mellitus (GDM) results from
a combination of genetic factors and environmental influences. Some susceptibility gene loci
associated with T2DM also play a role in GDM. In a cross-sectional study, a positive correlation
was found between a history of diabetes mellitus in first-degree relatives and GDM occurrence.
The risk of GDM significantly increased in pregnant women with a family history of diabetes
mellitus in first-degree relatives (paternal line OR = 2.54; maternal line OR = 3.60) [23].
Another study by Moosazadeh et al. [24] estimated that pregnant women with a family history of
diabetes mellitus had a 3.46-fold higher risk of developing GDM compared to those without a
family history. Our study revealed a higher incidence of a history of diabetes mellitus in first-
degree relatives in the GDM group compared to the non-GDM group, with / higher risk of GDM
in pregnant women with a family history of diabetes mellitus in first-degree relatives compared
to those without such history.

History of abortion and GDM

A history of abortion were more likely to have a premature delivery (0.99% VS 0.45%),
gestational diabetes mellitus (GDM) (13.40% VS 10.29%), placenta abnormality (8.16% VS
5.06%), placenta previa (5.65% VS 3.75%), placenta accreta (0.18% VS 0.04%), and placenta
adhesion (2.79% VS 1.03%) than those who obtained singleton pregnancies without a history of
abortion [7].

SCH and GDM

Hypothyroidism not only poses a risk for gestational diabetes mellitus (GDM) and preeclampsia
but is also linked to early abortion and fetal malformation. It has been reported that subclinical
hypothyroidism (SCH) during pregnancy is associated with a higher risk of gestational
hypertension, premature rupture of fetal membranes, intrauterine growth restriction, and low
birth weight [30]. The onset of SCH triggers the translocation of glucose transporter-4 on the
surfaces of adipose and muscle cell membranes, inducing multiple factors related to insulin
resistance. These factors include a decreased glucose transport rate in insulin-stimulated
monocytes, elevated free fatty acids, and reduced levels of serum selenium, ultimately leading to
increased blood glucose levels. Insulin resistance becomes evident during SCH [32].

While previous research established a 50% increased risk of GDM in pregnant women with SCH
compared to those with normal thyroid function [33], a meta-analysis reported an even higher
increase of 55.8% [34]. Surprisingly, our present study did not confirm gestational SCH as a
significant risk factor for GDM, aligning with the findings of Plowden et al. [35] and Furukawa
et al. [36]. In our study, the incidence of SCH was 13.20%. Thus, further studies are warranted to
delve into the intricate association between SCH and GDM.

Blood glucose and GDM

The peak of blood glucose during pregnancy is more frequent compared to non-pregnancy, and
the peak time is delayed, which may be related to diverse insulin antagonistic factors during
pregnancy. The rate of missed diagnosis will be augmented if the single FBG is used to screen
GDM. Corrado et al. reported that the FBG during early pregnancy was unvalued in the
diagnosis of GDM; FBG was the high-risk factor of GDM only if its level was ≥5.1 mmol/L
during early pregnancy [37]. Nevertheless, Li et al. found that FBG in the early stage of
pregnancy could be used to predict the occurrence of GDM [38]. Our results indicated that the
initial FBG and 2-h blood glucose by OGTT and HbA1c had strong correlation with the
occurrence of GDM, which might be caused by the early lifestyle intervention on the pregnant
women with higher FBG.
Other factors and GDM

The age of the mother, elevated BMI, a family history of diabetes, and being multigravidae are
significant factors that can predict the likelihood of gestational diabetes mellitus (GDM) [5].
There were no significant differences observed in the marital status, education level, and
occupations between individuals with gestational diabetes mellitus (GDM) and those without
(HPW) [6]. Previous studies revealed that multiple pregnancies [41] are the GDM-related
independent risks. In our investigation, the prevalence of gestational diabetes mellitus (GDM)
was observed to be higher among grand multiparous women (67.2%) compared to the
primiparous group (32.8%) of GDM subjects.

This study also demonstrated that women who were housewives (76.2%) in the GDM subjects
were significantly higher as compared to non GDM subjects [p <0.001, OR: 18.42, 95% CI:
7.436-45.669]. Women in low level of socioeconomic status are generally housewives or have a
job that does not take much of their lives. Being employed and busy were the main factors in
non-compliance of diabetes patients with treatment (14). The urban population has shown a very
high prevalence of inadequate vegetable and fruit consumption (92%), insufficient physical
activity (14%), and overweight and obesity (34%) [17]. It this study also observed that
socioeconomic status, education does not affect the prevalence of GDM. In our study, however,
no significant association was found between the educational level and the risk of GDM, which
might be related to the enrolled research subjects with a universally-higher educational level.
Data was collected through questionnaire which had information about sociodemographic risk
factors.

Hemoglobin (anemia) and GDM

A study initially linked anemia with gestational diabetes mellitus (GDM) [6], but this
association lost significance after adjusting for relevant factors. In a retrospective case-control
study, Lao and colleagues found that anemia was significantly associated with a lower
prevalence of GDM [49]. Given the connection between elevated ferritin concentration in GDM
and logical assumptions, it was hypothesized that pregnant women with anemia would exhibit a
reduced likelihood of GDM [50]. The lower prevalence of GDM in anemic pregnant women may
be attributed to the combined effects of iron deficiency [49]. Our study demonstrates a
significant difference in hemoglobin levels between the GDM and non-GDM groups (p < 0.001).
Excess iron appears to impact insulin synthesis and secretion, promoting lipid oxidation, which
in turn reduces glucose utilization in muscles and increases gluconeogenesis in the liver. This
cascade leads to liver-mediated insulin resistance [51]. This suggests a need to reevaluate routine
iron prescription for non-anemic pregnant women.

Summary, Five hundred were diagnosed with GDM on the basis of their results and the
prevalence was 17%. 76% of service housewives were GDM subjects. 75% of women had the
family history of hypertension. 85% of the women had a family history of T2DM (either mother
or father or both). The mean of maternal of the women with GDM was 30±4 years. Women’s
age in years (<25 and ≥25) based on the median age of the study population; BMI was 31.23±4.6
kg/m² while 60.60% were obese, 32.4% were overweight and only 7% had ideal body weight as
per the WHO guideline. BMI categorized (< 24.5 and ≥24.5) based on previous study and BMI
≥24.5 was significantly higher. Mean of GDM onset (weeks) stage during pregnancy was
24±2.4. 67% of GDM women had multi gravida (number of total confirmed pregnancy) and 25%
of the women had history of abortion. Termination weeks of delivery of GDM subjects were
36±2. High rate of caesarian delivery. Baseline clinical profile of GDM subjects; mean±SD of
75g fasting glucose (mmol/l) was 6.4±.7 and Serum 2h after glucose(mmol/l) level was
9.5±[Link] of HbA1c at first visit was 7.3±0.9 where 33.80% of woman had poor control,
15.10% fair control, 13.60% good control. Mean of Hemoglobin was 10.7±1. 20% of GDM
patients had hypothyroidism (TSH= 2.6± 2.0). The results of Logistic regression analysis
revealed that the age (>25), occupation (service holder), body mass index (BMI) (>24.5), parity
(multi), history of diabetes mellitus in first-degree relatives, family history of hypertension,
history of abortion, FSG, 2hrAG in GDM group was significantly higher compare to non-GDM
group, Hemoglobin and hypothyroidism were statistically insignificant but remarkably lower
compare to non GDM subjects. Socioeconomic status, education level was not significantly
different.

C. GDM associated maternal outcomes or complications (short-term and long-

term)
For short-term study,

This study investigated short-term maternal adverse outcomes during the pregnancy period,
specifically focusing on complications associated with gestational diabetes mellitus (GDM).
These complications included preeclampsia, pregnancy-induced hypertension (PIH), preterm
delivery, premature rupture of membranes (PROM), wound infection, polyhydramnios,
oligohydramnios, and cesarean section.

In this study, 2.6% of GDM subjects experienced preeclampsia, whereas no cases were reported
in the non-GDM group (0%, n=0). The calculated odds ratio is 0.619, suggesting that GDM
patients have approximately 1 times the chance of experiencing preeclampsia compared to non-
GDM individuals. The incidence of other adverse outcomes such as premature rupture of
membranes (PROM) at 3.6%, wound infection at 10.2%, polyhydramnios at 3.8%,
oligohydramnios at 3.0%, and cesarean delivery at 100% (n=500). Significant differences were
observed for all these outcomes between the GDM and non-GDM groups. It's important to note
that the reported percentages may appear low due to effective patient treatment; otherwise, they
might have been higher. While preterm delivery was reported in 7.8% of GDM patients,
compared to 4.3% in non-GDM patients, this difference did not reach statistical significance.
High rate of caesarian deliveries (100%) on GDM subjects compared to non GDM subjects
(53.3%). In our study, we found that 75% subjects had a family history of hypertension (chronic
hypertension in the father or mother) affected the risk of preeclampsia and gestational
hypertension.

In this study, risk factors such as increasing age (≥25) and uncontrolled FSG prior to delivery
strongly associated with preeclampsia. In numerous previous studies, GDM is consistently linked
independently to Preeclampsia in singleton pregnancy, while pre-pregnancy BMI and blood
glucose levels closely correlate with PE occurrence. GDM and PE, common pregnancy
complications, share risk factors such as obesity, advanced age, and multiple pregnancies [1, 2].
Pathophysiological processes in both conditions involve oxidative stress, pro-inflammatory
factor release, and vascular endothelial dysfunction, escalating the risk of future maternal
diabetes and cardiovascular disease [5–8], suggesting a potential correlation between GDM and
PE. Clinical manifestations may resolve early post-pregnancy, yet due to systemic pathological
changes, women with GDM or preeclampsia history face a heightened risk of developing type 2
diabetes or chronic hypertension [13].

FSG (5.1-6.9) 20-23wks in pg, associated with premature rupture of membrane (PROM).
PROM is one of the most common maternal complications in women with GDM and is
associated with poor glycemic control. Up to date, the association of PROM with glycemic
control in GDM patients is unclear. Our study suggested that the poor control of FSG may
induce changes in some factors, which ultimately promotes PROM. These factors are probably
those involved in glycolysis and fatty acid synthesis. Indeed, a previous study on metabolite
changes in the vagina of women with PROM indicated that glycolysis was the main metabolic
pathway that is down regulated in PROM (Liu et al. 2021). In patients with poor PPG control,
the prenatal BMI level was the only demographic factor that had a remarkable association with
glycemic control (p = .013).

History of abortion associated with premature rupture of membrane (PROM). Gestational

diabetes mellitus and having a previous history of abortion were significantly associated with
preterm premature rupture of membrane. The magnitude of preterm premature rupture membrane
is 6.6%. Having gestational diabetes mellitus (OR: 5.99, 95% CI: 1.01, 32.97) and previous
history of abortion (OR: 5.31, 95% CI: 1.06, 26.69) were found to be significantly associated
with preterm premature rupture of membrane [10].

In my study, observed that Gravida (multi) [54.7%, p=0.044] associated with pregnancy induced
hypertension. Previous study showed that Null parity, multiple pregnancies, a background of
chronic hypertension, gestational diabetes, fetal malformations, obesity, maternal age at extremes
(less than 20 or over 40 years), previous occurrences of PIH in pregnancies, and chronic
conditions such as renal disease, diabetes mellitus, and cardiac disease, along with undetected
chronic hypertension, positive family history indicating genetic susceptibility to PIH,
psychological stress, alcohol consumption, rheumatic arthritis, extreme underweight or
overweight, asthma, and a lower socioeconomic status are identified as risk factors for PIH
[5,10,11].

History of abortion (15.1%, p=0.073), had negative correlation with pregnancy induced
hypertension, poor control of 2hAG in first trimester associated with preterm delivery and wound
infection in GDM subjects. As of my last knowledge update in January 2022, there isn't a direct
and well-established relationship between the history of abortion and hypertension in patients
with gestational diabetes mellitus (GDM). A history of abortion was associated with an increased
risk of GDM in pregnant women, which may be a risk factor for predicting GDM[11]

Diabetes is associated with several pathological changes that contribute to poor wound healing.
Chronic hyperglycemia damages vasculature and hinders proper blood perfusion. Research
indicates that gestational diabetes mellitus may be linked to an increased incidence of infections,
such as vaginal infections, urinary tract infections, and chorioamnionitis [9,15,16]. Due to its
association to a poor metabolic control, higher body mass index, impaired leukocyte function,
and a change in vaginal pH [9,17–20], some studies suggest that gestational diabetes mellitus is
linked to disturbances in the vaginal flora and vaginal infections [21–25].

Summary, In this study, risk factors such as increasing age (≥25) and uncontrol FSG prior to
delivery strongly associated with preeclampsia, FSG (5.1-6.9) 20-23wks in pg, History of
abortion associated with premature rupture of membrane (PROM). Gravida (multi), history of
abortion, uncontrol FSG in first trimester associated with pregnancy induced hypertension, poor
control of 2hAG in first trimester associated with preterm delivery and wound infection.

For long-term study,

Higher BMI (>24.5) and WHR (91%) during later life after delivery, Gravida (multi) and
unhealthy life style are risk factors for long term outcomes of mother. GDM patients of this
study, about 52% subjects were converted to type2 diabetic patient within 1to 6 yrs. This
happened due to lack of awareness (less follow-up, less physical activity and dietary
management). They are suffering various problems as diabetic retinopathy. Abnormal liver
function l

A. GDM associated Neonatal outcomes or complications (short-term and long-term) and

Impact of Risk Factors on Neonatal consequences in Women With Gestational Diabetes Mellitus

B.
Hypertension????
Preeclampsia

PIH

Preterm delivery

PROM

Wound infection

Polyhydramnios

Oligohydramnios

Cesarian
hypertension

D. GDM associated neonatal outcomes or complications (short term and long

term)

E. Impact of Risk Factors on Short and Long-Term Maternal and Neonatal

consequences in Women With Gestational Diabetes Mellitus