ABSTRACT
Background: In most pregnant
women there is a counter effect of increased insulin secretion to
normalize glucose levels in their bodies. However, when the capacity of insulin
secretion is not large enough to overcome the effect of insulin resistance,
glucose intolerance develops resulting in gestational diabetes mellitus (GDM).
Aim: The main objective of this
study is to assess the role of first trimester glycated hemoglobin and
placental peptides as potential predictors of gestational diabetes. Research
design and methods: After 12 to 16 hours fasting, venous blood samples were
taken from 200 pregnant women (150non-diabetic and 50 type 2 diabetics)
into labeled yellow top gel-separator vacutainer tubes and centrifuged to
separate serum from blood cells. All serum samples were analyzed for lipid
profile, insulin and β-HCG, Progesterone, estradiol and human placenta
lactogen, whilst glucose levels were measured immediately with glucometer. The
A1 fast fraction – cation exchange method was used to estimate the level of
glycated hemoglobin. OGTT was performed for the non-diabetic pregnant women at
the 24th-28th week of gestation for the diagnosis of
Gestational Diabetes mellitus (GDM).
Results: Blood glucose, Glycated
hemoglobin (HbA1c), and BMI were significantly (P < 0.05) increased
in the pregnant women with diabetes as compared to the non-diabetics. Insulin,
β -HCG and HPL were higher in the diabetics than the non-diabetics, however, the
difference in insulin and HPL levels between control and diabetics (newly
diagnosed GDM) was statistically significant (P < 0.05). A prevalence of 8%
GDM was observed in the non-diabetic pregnant women with 58.3% of them aged
between 30-39years.Among study subjects with GDM, 25% (3) had family history of
diabetes. The risk of developing GDM is high with ageing (OR= 1.02, P = 0.757)
and overweight (OR=1.76, P = 0.370). The area under the ROC curve for FBG-1 (first
trimester test) was 0.49 suggesting that fasting plasma
glucose is a poor test for predicting GDM in the first trimester. However, AUC
for FBG-2 was 0.99 (24wks-28 wks) showing that FBG-2 is a very good test and
insulin, ß - HCG, P4, E2 and HPL averagely good for diagnosing GDM.
Conclusions: The overall
prevalence of GDM in this study was 8.0 %. Fasting plasma glucose may be
useful as a screening test for GDM on account of its high Specificity; however,
an additional test may be necessary to decrease the false negative test
results. HbA1c, insulin, β -HCG, P4, E2 and HPL are fair tests to predict GDM.
CHAPTER ONE
INTRODUCTION
1.1 BACKGROUND
Pregnancy is a physiological condition that coexist with
insulin resistance (Dahlgren, 2006) as
a result of decrease in accepted levels of insulin concentration in the
body(Baban et al., 2010). Most pregnant women exhibit a
counter effect of increased insulin secretion to offset high glucose levels in
fetal development. However, impaired insulin secretion or its low level during
gestation could lead to high glucose levels in the body and subsequently the
development of gestational diabetes mellitus (Shalayel et al.,
2011).
Gestational diabetes mellitus (GDM) is defined as a glucose
intolerance of varying levels of severity usually during the second or third
trimester of pregnancy (Shalayel et al., 2007; Kaaja and Ronnemaa, 2008; Shalayel et al.,
2010). Diagnosis of an individual with previous glucose intolerance
condition in pregnancy is usually confirmed when glucose tolerance test is
normal at postpartum (Metzger et al., 2007). GDM may
present with long-term implications, such as subsequent development of type 2
diabetes and the risk of obesity or glucose intolerance in the mother and
offspring respectively (Barbour et al., 2007).
In Sub-Saharan Africa, as in the developed world, there is an
increasing prevalence of diabetes and cardiovascular diseases as well as other
non-communicable diseases. With this increasing awareness of the disease,
studies conducted on the issue are limited, especially in Ghana. Prevalence of
GDM ranges from 4-10% of all pregnancies globally. In Sub-Saharan Africa
prevalence has been reported from 0% among pregnant women in Tanzania to 9% in
Ethiopia. Incidence however differs due to variations in nutritional lifestyle
and variances in genetic patterns between populations (Metzger
et al., 2007).
Unlike type 1 diabetes, GDM comes with high levels of insulin
secretion in pregnant women. In pregnancy, the partial inhibitory effect of
peptides secreted by the placenta, such as oestrogen, cortisol and human
placental lactogen on insulin, could lead to GDM(Page et al.,
2002).The placental peptides inhibitory role on insulin is a physiological
adaptation to provide adequate nutritional requirements including glucose to
the growing fetus in pregnancy (Kautzky-Willer et al., 2001).
This adaptation or role of placental peptides may lead to the development of
gestational diabetes. There is evidence pointing to a justification of this
relationship (Kautzky-Willer et al., 2001). It has been
shown that, women with gestational diabetes, leptin levels are increased during
and after pregnancy, likewise babies born to these mothers (Kautzky-Willer
et al., 2001).
Many of the tests used currently for gestational diabetes
provide only an estimation of risk and therefore it is very important to
develop new prenatal screening tests that are more reliable and specific.
Efforts for first trimester detection of gestational diabetes is emerging to
relief individuals from the psychological anxiety and pathological trauma faced
by prospective parents which will require the use of biomarkers may for early
detection and diagnosis. Although peptides are very promising candidates, there
remains much to be learnt (Page et al., 2002). Placental
peptides increase in levels at various stages of pregnancy and play a role in
augmenting the onset of gestational diabetes. Maternal factors such as age,
parity and previous birth weight among others also have an effect on the
development of gestational diabetes.
Therefore, if there were a proper assessment of the various
risks as well as markers that may predict the onset of gestational diabetes
among pregnant women here in Ghana, it would in turn allow medical
practitioners to better manage patients and prevent many pregnancies associated complications. The current study aims
at assessing the role of placental peptides and maternal factors as potential
predictors of gestational diabetes among pregnant women in the Tema metropolis
of Ghana.
1.2 PROBLEM STATEMENT
Between 2-5% of pregnancies are complicated by diabetes, of
which 90% are classified as gestational diabetes mellitus (Ben‐Haroush et al., 2004).
These complications are associated with adverse maternal
and infantile outcomes (Ben‐ Haroush et al., 2004).Ability to
properly manage and improve outcome is largely dependent on the identification
of potential markers that may prove more reliable and specific in their
diagnostic value and may be useful for identifying patients at risk.A case for
early first trimester diagnosis is emerging to help the situation and peptide
markers may be able to fill this niche.
1.3 JUSTIFICATION
Sub-Saharan Africa, like the rest of the world, is
experiencing an increasing prevalence of diabetes alongside other
non-communicable diseases. With this increasing awareness of the disease,
studies conducted on the issue are limited, especially in Ghana. From 1999-2011
two studies were identified, one in Ethiopia (Seyoum et al.,
1999) and one in South Africa (Mamabolo et al., 2007).
Three other relatively older studies have also been identified and prevalence
ranges have been reported in a range from 0% among pregnant women in Tanzania
to 9% in Ethiopia. There is therefore an indication that further studies are
warranted in the subject area in Africa, to assess prevalence and risk factors
which will enable a better understanding and help in its prevention and
management. Gestational Diabetes Mellitus is characterized by glucose intolerance during pregnancy(Reece, 2010), of which the
onset or discovery of glucose intolerance during pregnancy is usually in the
second or third trimester (Shalayel et al., 2007). The
timing at which this is usually detected carries long-term implications on
management as well as for the subsequent development of type 2 diabetes in the
mother and increased risk of obesity and glucose intolerance in the offspring.
Placental peptides with good diagnostic value could be useful for identifying
patients at risk. Placental peptides may have a role to play in the
augmentation of gestational diabetes and this can be harnessed as predictive
markers for the development of gestational diabetes. A case for early first
trimester diagnosis is emerging to help reduce the psychological anxiety and
pathological trauma faced by prospective mothers. Peptide markers could be
explored to fill this niche (Page et al., 2002). Also, there is a gap in the fight to early detection
of gestational diabetes in Ghana. The most widely used approach is diagnosis
and management, a non-preventive approach. Moreover, incidence of gestational
diabetes is influenced by nutritional habits and differences in genetic
patterns between populations. Furthermore, if there were a proper assessment of
the various risks as well as markers that may predict the onset of gestational
diabetes among pregnant women here in Ghana, it would in turn help medical
practitioners to better manage patients and prevent the many associated
complications in pregnancy
1.4 MAIN OBJECTIVE
The main objective of this study is to assess the role of
first trimester glycated hemoglobin, placental peptides, and maternal factors as potential
predictors of gestational diabetes mellitus (GDM).
To determine the levels of glycated haemoglobin and placental
peptides in pregnant Ghanaian women.
To determine the role of placental peptides in the
augmentation of gestational diabetes.
To determine maternal factors that may be associated with the
onset of gestational diabetes.
To determine the prevalence of dyslipidaemia among pregnant
women.
To determine the relationship between placental peptides and
serum lipids in the augmentation of gestational diabetes.
1.6 NULL
HYPOTHESIS:
Glycated hemoglobin and placental peptides are not markers of
gestational diabetes.
1.7 ALTERNATIVE HYPOTHESIS:
Glycated hemoglobin and placental peptides are markers of gestational diabetes.
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