FIRST TRIMESTER GLYCATED HAEMOGLOBIN AND PLACENTAL PEPTIDES AS MARKERS OF GESTATIONAL DIABETES

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 (BenHaroush 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).


1.5 SPECIFIC OBJECTIVES
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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Item Type: Ghanaian Postgraduate Material  |  Attribute: 96 pages  |  Chapters: 1-5
Format: MS Word  |  Price: GH50  |  Delivery: Within 30Mins.
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