Gestational Diabetes Mellitus (GDM) : Current Concept and A Short Review

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Introduction

Gestational Diabetes Mellitus is defined as Carboh


ydrate intolerance resulting in hyperglycaemia of
variable severity with onset or first recognition during
pregnancy
1
. Women who become pregnant and who
are known to have diabetes mellitus before
pregnancy do not have gestational diabetes but
have "diabetes mellitus and pregnancy" should be
treated accordingly before, during and after
pregnancy.
Review of literatures and discussion:
Gestational diabetes affects 3-10% of pregnancies
depending on population studied
2,3
. No specific
cause has been identified , but it is that hormones
produced during pregnancy increase in women 's
resistance to insulin resulting in impaired glucose
tolerance.
When born to mother with gestational diabetes
babies are at increased risk of problem such as
being large for gestational age which may lead to
delivery complications, low blood sugar and
Jaundice. Women with GDM are at increased risk of
developing type 2 diabetes mellitus after pregnancy,
while their off spring are prone to develop childhood
obesity with type 2 diabetes in later life
4,5
.
One study has shown that Maternal gestational
diabetes mellitus increases the offspring's cardio
metabolic risk, and in utero hyperinsulinemia is an
independent predictor of abnormal glucose tolerance
in childhood
6
. In GDM cord blood leptin levels are
significantly higher, and a source other then fetal
adipocytes appears to contribute to this
7
. Women
diagnosed with GDM who had gestational weight
gain above the IOM guidelines have higher risk of
undesirable outcomes, including preterm delivery,
having macrosomic neonates, and cesarean
delivery. Women who gained below guidelines are
more likely to remain on diet control but have small
for gestational age neonates
8
. Maternal adipocyte
fatty acid binding protein (AFABP) concentrations
are significantly increased in GDM. The adipokine
might contribute to the increased metabolic and
cardiovascular risk of the disease
9
. Raised GGT
Level in an independent risk factor for GDM in high
risk pregnant women
10
.
Serum levels of adipocyte fatty acid binding protein
are increased in gestational diabetes mellitus
11
.
Another study suggest that moderate maternal
leisure time physical exercise during GDM
pregnancy may reduce the risk of delivery
12
. Visfatin
concentration is decreased in women with
gestational diabetes mellitus in the third trimester
13
.
Gestational diabetes mellitus (GDM) affects
approximately 4% of all pregnant women in the US
and represents 90% of all cases of diabetes mellitus
diagnosed during pregnancy. In addition of the
adverse pregnancy out comes associated with this
complication, a history of GDM predisposes women
to the future development of type 2 diabetes
mellitus
14
(T2DM)
The 24-hour glucose profile performed after the
diagnosis of GDM clearly distinguishes between low-
risk (diet-treated) and high-risk (insulin-treated) for
fetal macrodome in GDM pregnancies
15
. The
concentration of TNF alpha, leptin and adiponectin
may change studies are required to verify the
mechanism of this alteration and wheather the three
cytokines can be predictors for GDM at an early
stage of pregnancy
16
. There is a high incidence of
early postpartum AGR among Chinese women with
prior GDM. Beta-Cell dysfunction, rather than insulin
resistance or inflammation, is the predominant
contributor to the early onset and Consistent AGR
after delivery
17
. In a community based study the
prevalence of GDM varied in urban,semiurban and
rural areas, Age>25years,BMI>25 and family history
were found to be risk factors for GDM
18
. There is
high incidence of early post partum AGR among
Chinese women with prior GDM,Beta cell
dysfunctionrather than insulin resistance or
inflammation is the predominant contributor to the
early onset and consistent AGR after delivery
19
.
Psychosocial constructs such as social support and
self sufficiency are associated with physical activity
and dietary habits. However association with BMI is
weak
20
.
Pathogenesis of GDM
The exact mechanism of development of GDM is
unknown. However the main feature of GDM is
increased insulin resistance. Pregnancy hormones
and other related factors are thought to interfere with
the action of insulin as it binds to the insulin
receptor. The interference occurs at the level of cell
signaling pathway behind the insulin receptor. Since
insulin promotes entry of glucose into cells, insulin
resistance prevents glucose from entering the cell
properly. As a result glucose remains in the blood
stream where glucose level rise. More insulin is
needed to overcome this resistance.
Insulin resistance is a normal phenomenon
emerging in the second trimester of pregnancy,
which progresses thereafter to levels seen in non
pregnant patients with type 2 diabetes.
Because glucose travels across the placenta
through diffusion facilitated by GLUT 4 carriers the
fetus is exposed to higher levels of blood glucose.
This leads to increased fetal level of insulin, insulin
itself can not cross the placenta. The growth
stimulating effect of insulin can lead to excessive
growth and a large baby (Macrosomia).

Effect of insulin on glucose uptake and metabolism.
Insulin binds to its receptor (1) on the cell membrane
which in turn starts many protein activation
cascades (2). These include: translocation of Glut-4
transporter to the plasma membrane and influx of
glucose (3), glycogen synthesis (4), glycolysis (5)
and fatty acid synthesis (6).
Source: Wikipedia.
Some risk factors associated with the
development of GDM
a. previous diagnosis of gestational diabetes or
prediabetes, impaired glucose tolerance or
impaired fasting glycaemia.
b. a family history having a first degree relative with
type 2 diabetes.
c. Increase Maternal age- a women's risk factors
increases as she gets older (especially for
women over 35 years of age)
d. ethnic background (those with higher risk factors
include African-Americans, Afro-Carribians,
Native Americans, Hispanics, Pacific Islanders,
and people originating from the Indian
subcontinent)
e. overweight, obese or severely obese increases
the risk by a factor 2.1,3.6 and 8.6 respectively.
f. previous pregnancy which resulted in a child with
a high birth weight(>90th centile, or >4000g (8lbs
12.8 oz)
g. previous poor obstetric history
In addition to this statistics show a double risk of
GDM in smokers. Polycystic ovarian syndrome is
also a risk factors, although relevant evidence
remains controversial. Some studies have looked at
more controversial potential risk factors, such as
short stature
33
.
About 40-60% of women with GDM have no
demonstrable risk factor; for this reason many
advocate to screen all women.Typically women with
gestational diabetes exhibit no symptoms, but some
women may demonstrate increased thirst, increased
urination, fatigue, nausea and vomiting, bladder
infection, yeast infections and blurred vision.
Tests for GDM
a. Non Challenge blood glucose tests: like
Fasting plasma glucose, 2 hour post prandial (after
meal) glucose test, Random glucose test if the FBG
is above 126mg/dl (7.0mmol/l) and post prandial
value above 200mg(11.1mmol/l) and it is confirmed
on subsequent day then the diagnosis of GDM is
made and no further testing is made.
b. Screening glucose challenge test: around 24-
28 weeks of gestation, if the test result is outside
normal limit then after that
c. Oral glucose Tolerance test(OGTT): after
overnight fasting between 8 to 14 hours. During the
three previous days the subject must have an
unrestricted diet containing at least 150gm
carbohydrate per day and unlimited physical activity.
The subject should remain seated during the test
and should not smoke throughout the test.
d. Urinary testing for glucose: Women with GDM
may have high glucose levels in their urine
(glycosuria).
Increased glomerular filtration rates (GFR) during
pregnancy contribute to some 50% of women having
glucose in their urine on dipstick tests at some point
during their pregnancy. The sensitivity of glycosuria
for GDM in the first 2 trimesters is only around 10%
and the positive predictive value is around 20%.
Complications of GDM
GDM carries risk to both mother and child. This
risk is largely related to high blood glucose levels
and its consequences. The risk increases with
higher blood glucose levels. Treatment resulting in
better control of these levels can reduce some of the
risks of GDM considerably.
The two main risks of GDM imposes on the baby are
growth abnormalities and chemical imbalances after
birth, which may require admission to a neonatal
intensive care unit. Infants born to mothers with
GDM are at risk of being both large for gestational
age (macrosomic) and small for gestational
age
21,22,23,24
.
Macrosomia in turn increases the risk of
instrumental deliveries (e.g. forceps, ventouse and
caesarean section) or problems during vaginal
delivery (such as shoulder dystocia). Macrosomia
may affect 12% of normal women compared to 20%
of patients with GDM. However, the evidence for
each of these complications is not equally strong; in
the hyperglycemia and Adverse pregnancy
outcome(HAPO) study for example, there was an
increased risk for babies to be large but not small for
gestational age. Research into complications for
GMD is difficult because of the many confounding
factors (such as obesity). Labelling a women as
having GMD may in itself increase the risk of having
a caesarean section
25,26,27,28
.
Neonates are also at an increased risk of low blood
glucose(hypoglycemia), jaundice, high red blood cell
mass(polycythemia) and low blood calcium
(hypocalcemia) and magnesium (hypomagnesemia).
GDM also interferes with maturation, causing
immature babies prone to respiratory distress
syndrome due to incomplete lung maturation and
impaired surfactant synthesis
29
.
Unlike pre-gestational diabetes, gestational diabetes
has not been clearly shown to be an independent
risk factor for birth defects. Birth defects usually
originate sometime during the first trimester (before
the 13th week)of pregnancy, whereas GDM
gradually develops and is least pronounced during
the first trimester. Studies have shown that the
offspring of women with GDM are at higher risk of
congenital malformations. A large case control study
found that gestational diabetes was linked to women
with a higher body mass index(>25 kg/ m2). It is
difficult to make sure that this is not partially due to
the inclusion of women with pre-existent type 2
diabetes who were not diagnosed before pregnancy.
Because of conflicting studies, it is unclear at the
moment whether women with GDM have a higher
risk of pre eclampsia. In the HAPO study, the risk of
pre eclampsia was between 13% and 37% higher,
although not all possible confounding factors were
corrected.
Prognosis of GDM
Gestational diabetes generally resolves once the
baby is born. Based on different studies the chances
of developing GDM in a second pregnancy are
between 30-84%, depending on the background. A
second pregnancy within 1 year of the previous
pregnancy has a high rate of recurrence. Women
diagnosed with GDM have an increased risk of
developing diabetes mellitus in future. The risk is
highest in women who needed insulin treatment ,had
antibodies associated with diabetes such as
antibodies against glutamate decarboxylase, islet
cell antibodies and or/insulinoma antigen., women
with two previous pregnancies, and women who are
obese. Women requiring insulin to manage GDM
have a 50% risk of developing diabetes within next 5
years. In some other studies the risk of developing
diabetes is 6 years in 50% cases and 70% had
diabetes developed after 28 years. In another study
in Navajo women , the risk of developing diabetes
after GDM is 50-70% after 11 years. Another study
showed the risk of diabetes after GDM is 25% after
15 years. In populations with low risk for type 2, in
lean subjects and in patients with auto antibodies
there is a higher rate of developing type1 diabetes.
In children of women having GDM increased risk of
childhood and adult obesity and the risk of
development of type2 diabetes in later life.In a atudy
in Jerusalem 410 out of 37962 patients reported to
have GDM there was tendency towards more breast
and pancreatic cancer among the children
31,32
.
Classification:
There are two 2 subtypes of gestational diabetes
(Diabetes which began during pregnancy according
to Pricilla White):
30
1. Type A1: abnormal oral glucose tolerance
test(OGTT) but normal blood glucose levels during
fasting and 2 hours after meals; diet modification is
sufficient to control glucose levels
2. Type A2: abnormal OGTT compounded by
abnormal glucose levels during fasting and/ of after
meals; additional therapy with insulin or other
medications is required.
Treatment:
The goal of treatment is to reduce the risks of GDM
for mother and child. Controlling glucose levels can
result in less serious fetal complications (such as
macrosomia) and increased maternal quality of life.
Counselling before pregnancy (for example, about
preventive folic acid supplements) and
multidisciplinary management are important for good
pregnancy outcomes. Most women can manage
their GDM with dietary changes and exercise. Self
monitoring of blood glucose levels can guide
therapy. Some women will need anti diabetic drugs,
most commonly insulin therapy.
Any diet needs to provide sufficient calories for
pregnancy, typically 2,000-2,500 kcal with the
exclution of simple carbohydrates. The main goal of
dietary modifications is to avoid peaks in blood
sugar levels. This can be done by using slow
release carbohydrate sources. Since insulin
resistance is highest in mornings, breakfast
carbohydrates need to be restricted more.
Regular moderately intense physical exercise is
advised, although there is no consensus on the
specific structure of exercise programs for GDM.
Self monitoring can be accomplished using a
handheld capillary glucose dosage system.
Compliance with these glucometer system can be
low. Target ranges advised
Regular blood samples can be used to determine
HbA1c levels, which give an idea of glucose control
over a longer time period.
If monitoring reveals failing control of glucose levels
with these measures, or if there is evidence of
complications like excessive fetal growth, treatment
with insulin might become necessary.
There is some evidence that certain oral glycemic
agents might be safe in pregnancy, or at least, are
significantly less dangerous to the developing fetus
than poorly controlled diabetes.
Metformin has shown promising results. Treatment
of polycystic ovarian syndrome with metformin
during pregnancy has been noted to decrease GDM
levels. A recent randomized controlled trial of
metformin versus insulin showed that women
preffered metformin tablets to insulin injection, and
that metformin is safe and equally effective as
insulin. Severe neonatal hypoglycemia was less
common in insulin-treated women, but preterm
delivary was more common. Almost half of patients
did not reach sufficient control with metformin alone
and needed supplemental therapy with insulin
compared to those treated with insulin alone, they
required less insulin and they gained less weight.
Conclusions
Although GDM is a very serious condition and there
is increased risk for mother and child in future to
develop obesity, type 2 diabetes. However proper
diagnosis, strict glycaemic control, diet
modifications with calorie restriction for obese ,
physical exercise, OHA, Self monitoring blood
glucose control etc can reduce the complications in
GDM. Efforts should be taken to follow up the
patients periodically with HbA1C, FBS, PPS, diet
chart and BMI etc to confront this.
References
1. http:en.Wikipedia.org/wiki.Gestational diabetes
2. American Diabetes Association.Gestational Diabetes
Mellitus.Diabetes Care 26:S103-S105,2003
3. Difinition,Diagnosis and Classification of Diabetes
Mellitus and its complications.WHO Technical report
Series, Part 1,Geneva,1999
4. Metzer BE,Coustan DR(Eds).Proceedings of Fourth
International Workshop Conference on Gestational
Diabetes Mellitus.Diabetes Care1998;21(Suppl 2):B1-
B167
5. CarrDB,Gabbe S.Gestational Diabetes: Detection,
Management and Implications. Clin Diabetes
1998;16(1):4
6. Tam WH, Ma RC, yang X, KO GT, Tong PC, cockram
CS, Sahota DS, Rogers MS, Chan JC Glucose
intolerance and cardio metabolic risk in children
exposed to maternal gestational diabetes mellitus in
utero. Pediatrics. 2008 Dec; 122 (06) 1229- 34.
7. Silva NY, Tennekoon KH, senanayake L, Karuna
nanaya EH. Cord blood leptin levels in normal
pregnancies, pregnancy induced hypertension and
gestational diabetes mellitus. Ceylon Med J. 2008
Sep; 53 (3) : 79- 82.
8. Theodoraki A, Baldeweg SE. Gestational diabetes
mellitus. Br J Hosp Med (Lond). 2008 Oct; 69 (10) :
562- 7.
9. Cheng YW, Chung JH, kurbisch- Block I, Inturrisi M,
Shafer S, Caughey AB.Gestational weight gain and
gestational diabetes mellitus: perinatal out comes.
Obset gynecol. 2008 Nov; 112 (5) : 1015- 22.
10. Tan PC,Muvarak S,Omar SZ. Gamma-glutamy I
traansferase level in pregnancy is an independent risk
factor for gestational diabetes mellitus. J Obstet
Gynaecol Res. 2008 Aug; 34 (4) : 512- 7.
11. Kralisch S etal. Serum levels of adipocyte fatty acid
binding protein are increased in gestational diabetes
mellitus.Eur J Endocrinol. 2009 jan; 160 (1) : 33-8,
Epub 2008 Oct 10.
12. Snapp CA, Donaldson Sk. Gestational diabetes
mellitus: physical exercise and health out comes .
Obstet Gynecol. 2008 Oct; 112 (4) : 868- 74.
13. Akturk M, Altinova AE, Mert I, Buyukkagnici U, sargin
A, Arslan M, Danisman N. Visfatin concentration is
decreased in women with gestational diabetes
mellitus in the third trimester J endocrinal Invest .
2008 Jul; 31 (7) : 610- 3.
14. Bentley-Lewis R, Levkoff S, Stuebe A, Seely
EWGestational diabetes mellitus: postpartum
opportunities for the diagnosis and prevention of type
2 diabetes mellitus.Nat clin pract Endocrinol Metab.
2008 Oct; (10): 552-8. Epub 2008Sep 9.
15. Suhonen L, Hiilesmaa V, Kaaja R, Teramo K.Detection
of pregnancies with high risk of fetal macrosomia
among women with gestational diabetes mellitus.Acta
obstet gynecol Scand. 2008; 87 (9): 940-5.
16. Gao XL, yang HX, zhao Y.Variations of tumor necrosis
factor-alpha, leptin and adiponection in mid-trimester
of gestational diabetes mellitus. Chin med J (Engl) .
2008 Apr 20; 121 (8) 701-5.
17. Cao XP, Xiao HP, chen SJ, Zhan YF, Xiu LL, Wang
ZL. Beta-cell dysfunction is the primary contributor to
the early postpartum diabetes among Chinese women
with history of gestational diabetes mellitus.Chin Med
J (Engl). 2008 Apr 20; 121 (8): 696-700.
18. Seshiah V, Balaji V, Balaji MS, paneerselvam A, Arthi T,
Thamizaharasi M, Datta M.Prevalence of gestational
diabetes mellitus in south India (Tamil Nadu) J assoc
physicians India. 2008 May; 56: 329-33.
19. CaoXPet al.Beta Cell dysfunction is the primary
contributor to the early postpartum diabetes among
Chinese women with history of Gestational Diabetes
Mellitus.Chin.Med.J(Engl).2008 Apr 20;121(8):696-
700
20. KimC,McEwen LN,Kieffer EC,Herman WH,Piette
JD.Self sufficiency,social support,and association with
physical activity and body mass index among women
with histories of gestational diabetes mellitus.
Diabetes Educ.2008 Jul-Aug; 34(4):719-28
21. HAPO study cooperative Research Group.Hypog
lycaemia and adverse pregnancy outcome. N Eng J
Med.2008; 358(19):1991-2002
22. Langer O,Rodiguez DA,Xenakis EM,McFarland
MB,Berkus MD, Arrendondo F.Intensified versus
conventional management of gestational diabetes.
Ame J Obst Gynecol 1994; 170(4):1036-46
23. Naylor CD,Sermer M,Chen E,Farine D. Selective
screening for gestational diabetes mellitus. Toronto
trihospital Gestational Diabetes Project Investigator.
J N Eng Med 1997; 337 (22); 1591.
24. Jovanovic - Peterson L, Bevier W, Peterson CM. The
Santa Barbara County Health care services program;
birth weight change concomitant with screeing for and
treatment of glucose-intolerance of pregnancy; a
potential cost - effective intervation? Am j perinatol
1997; 14 (4); 221 - 8
25. Jones CW Gestational diabetes and its impact on the
neonatal Netw. 2001; 20 (6); 17-23
26. Allen VM, Armson BA, Wilson RD, et al. Teratogenicity
associated with pre-existing and gestational
diabetes.J Obstet Gynaecol Can.2007; 29(11):927-34
27. Martinez-Frias ML,Frias JP,Bermejo E,Rodriguez-
Pinilla E,Prieto L,Frieas JL.Pre gestational maternal
body mass index predicts an increased risk of
congenital malformations in infants of mothers with
gestational diabetes. Diabet Med 2005; 22 (6):775-81
28. Leguizamon GF, Zeff NP, Fernandez A. Hypertension
and the pregnancy complicated by diabetes. Curr
Diab Rep 2006; 6(4): 297-304.
29. Kim C, Berger DK, Chamany S. Recurrence of
gestational diabetes mellitus: A systematic review.
Diabetes Care 2007; 30 (5):1314-9.
30. Agarwal MM, Dhatt GS. Fasting plasma glucose as a
screening test for gestational diabetes mellitus. Arch
Gynecol Obstet 2007; 275(2): 81-7.
31. Perrin MC, Terry MB, Kleinhaus K et al.Gestational
diabetes and the risk of breast cancer among women
in the Jerusalem Perinatal study.Breast Can Res
Treat.2007
32. Perrin MC, Terry MB, Kleinhaus K et al.Gestational
diabetes and the risk factor for Pancreatic cancer: a
prospective cohort study.BMC Med 2007;5:25
33. England LJ, Levine RJ,Qian C et al.Glucose tolerance
and risk of gestational diabetes mellitus in nulliparous
women who smoke during pregnancy.Ame J
Epidemiol 2004;160(12):1205-13
Review Article Bangladesh J Pathol 24 (1) : 16
Bangladesh J Pathol 24 (1) : 2009
Bangladesh J Pathol 24 (1) : 2009
Bangladesh J Pathol 24 (1) : 2009
Bangladesh J Pathol 24 (1) : 2009
Abstract
Gestational Diabetes Mellitus (GDM) is a very common and important disease occurring during pregnancy and has
detrimental effect on both the mother and the baby. The mother is at increased risk of developing obstetric
complications like prolonged labour, prone to develop type 2 diabetes in future and the baby is born with
overweight, cause of childhood obesity and later life development of type 2 diabetes. A short review and current
concept of GDM is discussed.
Key words: GDM, Type 2 diabetes, Obesity, Macrosomia,Complications
1. Dr. MT Rahman, Professor & Head, Pathology Department,Ibrahim Medical College For Correspondence
2. Dr T Tahmin, Lecturer, Pathology Department, Bangladesh Medical College, Dhanmondi,Dhaka.
3. Dr. S Ferdousi, Asstt Professor, Pathology Department, Ibrahim Medical College, Dhaka.
4. Dr. SN Bela, Associate Professor, Gynae Department , BIRDEM Hospital, Dhaka.
Gestational Diabetes Mellitus (GDM):
Current concept and a short Review
MT Rahman
1
, T Tahmin
2
, S Ferdousi
3
, SN Bela
4
MT Rahman, T Tahmin, S Ferdousi, SN Bela
Bangladesh J Pathol 24 (1) : 17
MT Rahman, T Tahmin, S Ferdousi, SN Bela
Bangladesh J Pathol 24 (1) : 18
MT Rahman, T Tahmin, S Ferdousi, SN Bela Bangladesh J Pathol 24 (1) : 19
MT Rahman, T Tahmin, S Ferdousi, SN Bela
Banglash J Pathol 24 (1) : 20
Bangladesh J Pathol 24 (1) : 2009

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