PATTERN OF BLOOD GLUCOSE AND PREGNANCY OUTCOME OF WOMEN

WITH GESTATIONAL DIABETES AT UNIVERSITY OF ILORIN TEACHING

HOSPITAL.

BY

DR AJIBOYE AKINYOSOYE DEJI (MBBS)

AF/005/14/007/519

UNIVERSITY OF ILORIN TEACHING HOSPITAL, ILORIN.

A DISSERTATION SUBMITTED TO THE NATIONAL POSTGRADUATE MEDICAL

COLLEGE OF NIGERIA IN PART FULFILLMENT FOR THE AWARD OF THE
FELLOWSHIP OF THE COLLEGE.

MAY 2017

i
 DECLARATION

I, Dr Ajiboye Akinyosoye Deji hereby declare that this dissertation is an original work. It has not
been presented or submitted to any other college or organization for any consideration.

--------------- -----------------------

Date Dr Ajiboye Akinyosoye D.

(RESEARCHER)

aakinyosoyeajiboye@gmail.com

08038131299

ii
 DEDICATION.

This book is dedicated to Almighty God, the source of inspiration, my hope, my joy and my
strength.

iii
 ATTESTATION:

(A) HEAD OF DEPARTMENT:

NAME: PROF O.R BALOGUN (FWACS)

SIGNATURE AND DATE……………………………

(B) FIRST SUPERVISOR:

NAME: DR ABDUL I.F. (FWACS)

SIGNATURE AND DATE………………………………

(C) SECOND SUPERVISOR

NAME: DR K.T. ADESINA(FMCOG, FWACS)

SIGNATURE AND DATE………………………………….

(D) THIRD SUPERVISOR

NAME: DR EZEOKE G.G(FWACS)

SIGNATURE AND DATE…………………………………..

(E) FOURTH SUPERVISOR

NAME; DR BILIAMINU A.S (FMC PATH)

CANDIDATE: DR AJIBOYE AKINYOSOYE DEJI

iv
 ACKNOWLEDGMENTS.

I want to appreciate and express my gratitude to my supervisors;Dr Adesina, Abdul, Dr Ezeoke

and Dr Biliaminu. They were always available to guide me and direct me appropiately, I cherish
your sincere support, concern and meticulous supervision. I also want to appreciate the Head of
department and entire staff of the department of Obtetrics and Gynaecology, without their
cooperation, this dissertation would not have been possible.

Many thanks goes to my family, my wife Bukola, thank you for bearing with my long and
regular absence from home and for taking wonderful care of the children;Mayokun and Ewa. I
thank my loving parents, Prince and Dr Ajiboye, for your nurture and guidance in life. I also
appreciate your mentorship Professor Chris,many thanks for being there for me.

To my friends and colleagues who have not given up on me, I appreciate you all.

v
ETHICAL CLEARANCE

vi
 ABBREVIATIONS

EGA Estimated Gestational Age

ELISA Enzyme Linked Immunosorbent Assay

FBS Fasting blood sugar

GDM Gestational Diabetes Melllitus

HAPO Hyperglycemia and Adverse Pregnancy Outcome study

HLA-G Human Leucocyte Antigen

HPL Human Placental Lactogen

IADPSG International Association of Diabetes and Pregnancy

Study groups

LMP Last Menstrual Period

NDDG National Diabetes Data Group

OGTT Oral Glucose Tolerance Test

PPARγ Peroxisome Proliferator-Activated Receptor Gamma

SMBG Self-monitoring of blood glucose

TNF-α Tumor Necrosis Factor- alpha

UITH University of Ilorin Teaching Hospital

WHO World Health Organization

vii
 TABLE OF CONTENTS

TITLE PAGE i

CERTIFICATION ii

DECLARATION iii

DEDICATION iv

ETHICAL CLEARANCE v

ABBREVIATIONS vi

ACKNOWLEDGMENTS vii

TABLE OF CONTENTS viii

ABSTRACT ix

CHAPTER 1: INTRODUCTION 1

CHAPTER 2: LITERATURE REVIEW 4

CHAPTER 3: AIMS AND OBJECTIVES 13

CHAPTER 4: METHODOLOGY 16

CHAPTER 5: RESULTS 23

CHAPTER 6: DISCUSSION 37

CONCLUSION 41

RECOMMENDATIONS 42

STUDY LIMITATIONS 43

REFERENCES 44

APPENDIX I: INFORMATION SHEET 53

APPENDIX II: CONSENT FORM 55

APPENDIX III: DATA COLLECTION SHEET 56

viii
 ABSTRACT

Background

Gestational diabetes mellitus is carbohydrate intolerance resulting in hyperglycemia of variable

severity with first onset or recognition in pregnancy. It is associated with increased maternal and
perinatal morbidity and mortality. It is important to accurately identify this condition in pregnant
women to ensure appropriate management.

Aim

To determine the prevalence of Gestational Diabetes Mellitus and perinatal outcome among
women attending antenatal clinics.

Methods

This was a prospective cross-sectional study. Subjects comprised of pregnant women between
24-28 weeks presenting for antenatal clinic visits without a prior diagnosis of diabetes mellitus.
Consenting women were evaluated using fasting plasma glucose and oral glucose tolerance test
also done between 24-28weeks for women with fasting plasma glucose values of ≤ 7mmol/l.
75grams of glucose in 300ml of water was used for the oral glucose tolerance test. A repeat
fasting plasma glucose was then conducted for these women between 36-38 weeks gestation

Results

Two hundred and fifteen women were recruited for the study. Twenty women had gestational
diabetes mellitus and the prevalence was 9% . The mean for the initial fasting plasma glucose
done was 3.87mmol/l, the mean value at the time of the OGTT was 4.04mmol/l and the value ,
two hours after 75gram of oral glucose was given was 5.78mmol/l. /l.

Glycosuria was found to be able to predict the onset of GDM 8 times over its absence. Body
mass index was also found to be statististically significant and was also able to predict the
occurrence of GDM,(Odds ratio of 8.351 and1.112 respectively).

ix
There was a statistical significance with the NICU admission, half of the babies born to women
with GDM had NICU admission.

Conclusion

Glycosuria and body mass index can serve as useful predictors for onset of the condition. GDM
was associated with adverse perinatal outcomes when the mode of delivery and NICU admission
was considered.

x
 CHAPTER ONE

INTRODUCTION

Gestational diabetes mellitus is carbohydrate intolerance resulting in hyperglycemia of variable

severity with first onset or recognition in pregnancy. It may be asymptomatic or present as overt
diabetes mellitus.1,2,3 In the post-partum state, unresolved gestational diabetes mellitus can
progress to Type 2 diabetes mellitus and its sequelae.4,5 It has been associated with adverse
pregnancy outcomes.6 The definition of this condition pre-supposes that the individual may
have unrecognized diabetes mellitus, or may have developed the diabetes mellitus coincidentally
with the pregnancy.4,5 The hallmark of gestational diabetes mellitus is insulin resistance and
absence of increased insulin release from the beta cells of the pancreas.7 This results in the
inability to regulate and utilize metabolic fuels like glucose and free fatty acids.5,8

Untreated disease can be disastrous to the developing fetus, leading to an increase in

miscarriages, congenital malformations, fetal macrosomia, increased risk of preterm deliveries
and shoulder dystocia. As a result of these, there may be birth injuries like Erb’s palsy. Other
problems such as perinatal asphyxia, electrolyte imbalances and hypoglycaemia can occur after
delivery. The mother is also at risk of vaginal lacerations, operative deliveries, postpartum
hemorrhage.7,9,10

Gestational diabetes is an endemic problem, though the prevalence is not known in many
countries, it is assumed to reflect the prevalence of pre-diabetes and type 2 diabetes in the
populations studied. 3 Prevalence ranging between 1.1%-14.3% have been quoted in developed
nations such as Australia and USA.2,11,12 In the developing nations, including Nigeria, most
studies quote prevalence between 0.15%-2.5%,13 however, a study from eastern Nigeria quoted
a prevalence of 4.8%.8

The most appropriate time for diagnosis remains controversial, however, the World Health
Organization14 recommends universal testing for gestational diabetes mellitus for all pregnant
women within 24-28 gestational age because of the asymptomatic nature and absence of classical
risk factors.15

xi
The Oral Glucose Tolerance Test (OGTT) has been the gold standard for diagnosis of gestational
diabetes over the decades, but there is no uniformity on how it is used and interpreted.16
In 1964, O’Sullivan proposed specific criteria for the interpretation of glucose intolerance and
identification of women at risk. This employed the use of 100grams of glucose solution; blood
glucose was measured before the ingestion of the glucose solution, then 1 hour, 2 hour and 3
hours after. GDM is diagnosed with values of greater than or equal to 5.8mmol/l, fasting, then ≥
10.0mmol/l; ≥ 9.1mmol/l and ≥ 8.0mmol/l for 1 hour, 2 hour and 3 hour blood glucose
samples.11 The criteria was revised and modified by Carpenter and Coustan and the modification
was accepted for use by the American Diabetes Association.17 Diagnosis is made with two or
more abnormal blood glucose value. The National Diabetic Data Group (NDDG) reviewed the
criteria in 1979, and suggested lower diagnostic values for its criteria, the effect of this was a
higher prevalence for gestational diabetes.18 The World Health Organization(WHO) diagnostic
criteria for hyperglycemia in pregnancy was formulated in 1999 and revised in 2006, however, it
did not consider women with fasting plasma glucose of less than 7mmol/l as having gestational
diabetes.19,20 The large scale ‘hyperglycemia and adverse pregnancy outcome (HAPO) study,
published in 2008 revealed that there are adverse perinatal outcomes can occur in those with
plasma glucose values less than 7mmol/l, in a dose dependent fashion.21 Based on the
recommendations of this study therefore, the World Health Organization recommended a two-
phase approach to recognizing and classifying hyperglycemic in pregnancy.22,23 The new
approach involves an initial phase of testing with fasting blood glucose assessment and a second
phase which involves a 2hour 75g Oral Glucose Tolerance Test at 24-28weeks.
With the new criteria by WHO published in 2013, gestational diabetes is diagnosed with an
initial fasting plasma glucose assay, any value greater than or equal to 5.1mmol/l is considered
abnormal, this will require an Oral Glucose Tolerance Test between 24-28 weeks gestation. The
plasma glucose will be determined before and 2 hours after the administration of 75grams of
glucose solution. Gestational diabetes will be considered also when the plasma glucose value two
hours after the glucose load is greater than or equals to 8.5mmol/l. 24,25 In a bid to increase the
strength of the study, further testing was conducted on women with normal plasma glucose
levels in the late third trimester, usually between 36-38 weeks when insulin resistance is
expected to be at its peak,26,27

xii
Nigeria and the rest of Sub-Saharan Africa, has no consensus on any protocol for the diagnosis
of gestational diabetes, the studies that have been done have used a combination of risk factors in
diagnosis and different protocols have been used. 20 More so, there hasn’t been the replication of
any large scale study like the HAPO study in our region, in spite of the increasing importance of
diabetes as a major cause of morbidity and mortality among women of reproductive age group.
The use of a risk factor analysis and plasma glucose sampling was used in this study to identify
women with gestational diabetes.

xiii
 CHAPTER TWO

LITERATURE REVIEW

2.1 INTRODUCTION

Gestational diabetes mellitus is one of the commonest medical conditions during pregnancy,
occurring in 3-10% of pregnancies.7 It is first diagnosed in pregnancy and usually many will
become normoglycaemic in the postpartum period.20 Hyperglycaemia during pregnancy is
associated with various maternal and perinatal adverse outcomes.13 The detection of gestational
diabetes provides an opportunity to identify women at risk of short term and long term
complications. The recommended timing for diagnosis of GDM is 24-28 weeks of pregnancy.16

2.2 Burden of Gestational Diabetes

Gestational diabetes is an endemic problem. Although the prevalence is not known in many
countries, it is assumed to reflect the prevalence of pre-diabetes and type 2 diabetes in such
studied populations 3. Prevalence generally ranges between 1.1%-14.3%.11,14 The figures
however varies, depending on the diagnostic criteria used and population studied. In
developing nations, including Nigeria, most studies quote prevalence between 0.15%-2.5%,12
however, a study from eastern Nigeria quoted a prevalence of 4.8%.8 The prevalence of
gestational diabetes is on the rise and increasingly a prevalent risk factor for the development of
Type 2 diabetes and their offsprings have a life-long increase risk of glucose intolerance, obesity
and metabolic syndrome.13

2.3 PATHOPHYSIOLOGY OF GESTATIONAL DIABETES

Normal pregnancy has characteristics of a "diabetogenic state" because the physiologic changes
that occur reset glucose homeostasis in the general direction of hyperglycemia. This is due to the
increased insulin resistance commonly seen in the late second and third trimesters.21 The first
half of pregnancy however is characterized by increased insulin sensitivity which leaves the
fasting plasma glucose relatively unchanged.2 In the second half of pregnancy, there is increased
xiv
insulin resistance.22 The Insulin resistance is due to increased placental secretion of anti-insulin
hormones such as estrogen, progesterone, cortisol and human placental lactogen 2. The human
placental lactogen (HPL) in particular is responsible for increased hunger sensation and diversion
of maternal carbohydrate metabolism in the third trimester.2,22 This results in an elevated level of
circulating maternal substrates to meet the needs of the rapidly growing fetus. In a normal
pregnancy, the net result of this metabolic shift is increased maternal secretion of insulin to
maintain normal glycaemic levels.2 Gestational diabetes typically develops in the second half of
pregnancy among women who are unable to adapt successfully to these changes. In them, there
is a reduced insulin response because of β-cell dysfunction which is relative to the degree of
insulin resistance.22,23 The features of β-cell dysfunction include impaired first phase insulin
secretion, prolonged and increased second-phase insulin release, increased hepatic glucose
output, changes in insulin kinetics and defective insulin secretion. These reduces insulin response
to meals unlike in unaffected women.22,24 There is also evidence that chronic insulin resistance
predates pregnancy in women with gestational diabetes mellitus and it is independent of body
mass index.25,26

Aetiology

The exact cause of gestational diabetes is unknown; however the postulates include defects in the
insulin signaling pathway, reduced expression of peroxisome proliferator-activated receptor
gamma (PPARγ) and reduced insulin-mediated glucose transport in women with gestational
diabetes.27 Another postulate that has been proposed is the antigenic load caused by the fetus
itself. This happens when the Human Leucocyte Antigen G (HLA-G) which functions to protect
the fetus from immune attack by down-regulating cytotoxic T cell responses to fetal trophoblast
antigens inadvertently affects the pancreatic islet cells.28 Other speculated mechanisms in the
development of gestational diabetes include increased production of leptin and decreased
production of adiponectin. These tend to modulate appetite upwards, thus increasing the weight
gain in gestational diabetes patients.22 There is also evidence of increase in circulating
inflammatory markers such as tumour necrosis factor alpha (TNF-α), interleukin-6 and C-
reactive protein 29

xv
These pathophysiological abnormalities, in addition to improved socio-economic conditions and
intake of foods with high glycaemic indices, contribute to the emergence of gestational diabetes.

2.4 Predictors for Gestational Diabetes Mellitus

Epidemiological evidence for predictors or risk factors is limited. Potential risk factors
for gestational diabetes mellitus include advanced maternal age, pre-pregnancy obesity, body fat
pattern, excessive gestational weight gain, ethnic origin, adverse obstetric history, family history
of diabetes, dietary factors and a sedentary lifestyle.

i. Age

Blood glucose values have been observed to rise with age independently of weight.30 Therefore;
the likelihood of having glucose intolerance during pregnancy also increases with age. Age was
more strongly correlated with blood glucose levels than advancing gestation in one study by
31 32
Wilkerson and Sullivan in 1963. In another study by MacAfee and Beischer in1974, age
≥23 years was observed to be the strongest predictor .31,32 Though the mechanism by which age
raises glycaemic levels independent of other factors remains to be elucidated it has been proven
to be a strong predictor of developing Gestational Diabetes Mellitus.33

ii. Ethnicity

The incidence gestational diabetes mellitus has been observed to be higher among some ethnic
groups than others. This observation has been supported by several studies and findings vary
from country to country.1,3 In an ethnically heterogeneous sample of 10,187 women in the United
States, the following ethnic groups (Orientals, first generation Hispanics, Indian and Middle
Eastern women) had a significantly higher risk compared with Whites, after controlling for
maternal age, pre-pregnancy weight, history of infertility, prenatal care and family history of
diabetes.34 In a study among 11,205 women in a multi-ethnic clinic in London, women in the

xvi
Indian subcontinent had the highest relative risk, followed by women from Southeast Asia, the
Middle East and Africa compared with local White women after adjustment for age, parity and
obesity. 35

iii. Pre-pregnancy obesity

Obese pregnant women have higher fasting and post-prandial blood glucose and insulin levels
compared with lean pregnant women,24,36,37 High pre-gravid weight increases the risk,
independent of age, parity and ethnicity.34,35 Central obesity may impart a greater risk than
overall obesity.38 Both pre-pregnancy and gravid central fat patterns have been linked with an
increased risk.38 A unit increase in waist-to-hip ratio or waist circumference (cm) increased mean
2-h plasma glucose levels on a 75 g glucose load by 1.85 mmol/l and 0.016 mmol/L respectively
(p~0.02).39

iv. Pregnancy weight gain

Excessive weight gain during pregnancy may increase the risk .40 Studies have showed a
smaller increase in fasting and meal stimulated plasma insulin concentration from 16 to 36 weeks
gestation among obese non-diabetic women on an energy and carbohydrate-restricted diet,
compared with obese women on an unrestricted diet.41

v. Family history of diabetes

Women with a family history of diabetes may be at a 2 to 3-fold higher risk compared with
women without any such history.42,43 Offspring of women who had diabetes during pregnancy
had a higher prevalence of diabetes compared with offspring of women who were non-diabetic
during pregnancy but became diabetic after controlling for the effects of age, paternal diabetes
and age of maternal onset of diabetes.44

vi. Obstetric history

An adverse obstetric history, including previous gestational diabetes mellitus have increased risk
of developing gestational diabetes again.45 In a study among 10,187 multi-ethnic women, the
prevalence of the condition increased with a history of infertility, previous premature birth and
stillbirth.34 Women who had gestational diabetes mellitus in their previous pregnancy and
xvii
delivered a normal weight infant were 26 times more likely to have it in the current pregnancy. 46
The risk was also significantly elevated for women who had both GDM and macrosomic babies
in their previous pregnancy .47,48

vii. Diet

Diets rich in simple sugars have been linked to an increased risk of developing gestational
diabetes, whereas, complex carbohydrates have an opposing effect. Equally, vegetables, legumes
and diets rich in magnesium are associated with lower risks. Diets with low glycaemic indices
have been recommended to reduce the risk of developing gestational diabetes in those with other
confounding risks.49

viii. Physical activity

Cardiovascular exercise is known to increase glucose disposal by increasing insulin sensitivity

and binding to receptors. Several well controlled studies have demonstrated the protective effect
of increased physical activity on Type 2 diabetes,50,51 The risk was lower among women who
exercised at least once per week for 30 minutes or more during pregnancy compared with those
who do not.52,53

Though ample evidence exists for the risk posed by advanced maternal age and family history of
diabetes, these factors are however not modifiable. In order to help prevent the onset of
gestational diabetes, greater emphasis should be placed on understanding the contribution of
modifiable risk factors such as pre-gravid weight, pregnancy weight gain, dietary intake and
physical activity patterns to the disease.

2.5. DIAGNOSIS OF GESTATIONAL DIABETES

There is no international consensus regarding criteria for screening or diagnosis of Gestational

Diabetes Mellitus.1,16 The diagnostic criteria that have been proposed and utilized by various
organizations have been modification of the original work of O ‘Sullivan. The criteria have been
a subject of continued research to improve the perinatal and maternal morbidity and mortality.
However, there is a consensus on the timing of the test, which is between 24-28 weeks of
gestation.54,55

xviii
In the O ‘Sullivan criteria, 100gram of glucose was given orally with water after an initial fasting
plasma glucose was taken, blood samples were withdrawn at 1 hour;2 hours and 3 hours after
the oral glucose solution was taken. Values of ≥ 5.8mmol/l,fasting, and ≥ 10.0mmol/l; ≥
9.1mmol/l and ≥ 8.0mmol/l respectively, two or more values are considered diagnostic of
gestational diabetes.11-14 The test, when introduced, was primarily to distinguish those who were
susceptible to developing Type II diabetes later in life and not to prevent complications in the
index pregnancy. The initial test by O’ Sullivan and Mahan was based on venous blood samples.
But studies are now based on plasma samples.

World Health Organization criteria using the 75 g 2-h Oral glucose tolerance test, gestational
diabetes is diagnosed if the fasting value exceeds 7mmol/l or the 2-hvalue exceeds 7.8 mmol/l or
random value is 11.1mmol/l or more. There was a further modification of this criteria because
the initial criteria was not evidenced based.

The HAPO study, which was a large based Caucasian study, involving 25,000 participants,
highlighted the adverse outcomes with lower degrees of hyperglycemia. It showed a dose-
dependent relationship between hyperglycemia and adverse pregnancy outcomes.12,14

Based on the recommendations from the HAPO study, the WHO revised the criteria for
diagnosis of gestational diabetes:

Fasting plasma glucose = 5.1-6.9 mmol/l (92 -125 mg/dl)

1-h post 75g oral glucose load >10.0 mmol/l (180 mg/dl)

2-h post 75g oral glucose load 8.5 – 11.0 mmol/l (153-199 mg/dl) .18

2.6. Treatment strategies

The goal of treatment in gestational diabetes is to normalize blood glucose levels and
decrease adverse maternal and fetal outcomes associated with hyperglycemia. Dietary
intervention is the first line of treatment for gestational diabetes. Other treatment strategies which
may be used in combination include insulin therapy, exercise and blood glucose monitoring.

i. Energy restriction

xix
Energy restriction has been recommended for obese women with gestational diabetes; the aim is
to optimize blood glucose levels through restriction of gestational weight gain. Weight gain
restriction in obese pregnant women is also advantageous in minimizing post-partum weight
retention and risk for subsequent diabetes. Most clinicians recommend the use of moderate
energy restriction (100 kj/kg ideal body weight, 6276-7531 kJ/day) in treating obese women
having gestational diabetes.1,56

ii. Carbohydrate restriction

High post-prandial glucose levels have been shown to increase the risk for infant
macrosomia57,58. The current recommendations by the American Diabetic Association for
pregnant diabetic women specifies that energy intake from protein should constitute 10-20% of
total energy intake but the remaining 80-90% of calories can be distributed over carbohydrate
and fat, depending on individual needs.59 Besides the total amount of carbohydrates, the source
of carbohydrate may also be important. Complex carbohydrates that produce smaller glycaemic
excursions should make up the bulk consumed...60 It is difficult to quantify the calories in the
typical Nigerian diet because the glycemic index of most Nigerian foods are not known, however
in a study conducted in University of Benin, the glycemic index of some common Nigerian
meals were determined for a standardized serving size, and cassava starch was found to have the
highest glycemic index of 98.6±2.68, semovita 95.8±0.28 while cassava, processed as ‘Garri’
had the lowest glycemic index of 82.25±0.05 followed by ‘Amala’ a Yam based meal with
84.35±2.68. The low glycaemic index of Garri may be related to its processing as it contains
more fibre than the starch derivative.61

iii. Insulin therapy

Insulin therapy is usually initiated if dietary treatment alone is not successful in maintaining pre-
prandial and/or post-prandial euglycemia.1 Glycaemic thresholds for initiation of insulin therapy
vary across studies. Target glycaemic levels recommended by the Canadian Diabetic Association
to achieve optimal neonatal outcome are fasting: <5.3mmol/l, 1-h post-prandial: (7.8 mmol/l)
and 2-h postprandial: (6.7mmol/l).62 The American Diabetic Association recommends initiation
xx
of insulin therapy if plasma fasting glucose exceeds 5.8 mmol/l or 2-h post-prandial value
exceeds 6.7 mmol/l on two or more occasions over a 1-2 week period.60 The choice of insulin,
frequency of administration and dosage vary according to individual needs in maintaining
euglycaemia.

iv. Oral hypoglycemic agents.

Some recent meta-analysis have revealed that some oral hypoglycemic agents are as
effective as insulin in the management of gestational diabetes.63 Metformin, and glyburide have
been used widely and shown to be useful in control of hyperglycemia, and have been found not
to have any teratogenic effects.2

v. Self-monitoring of blood glucose (SMBG)

SMBG is an important aspect of the management of GDM, especially for women on

insulin therapy, as it provides immediate feedback regarding glycaemic levels, aids fast
recognition of hypo- or hyper-glycemia, helps in better control of plasma glucose, and reinforces
the relationship between portion sizes, food choices and glycaemic levels.1,64

vi. Exercise

Increased physical activity may improve glycaemic levels indirectly by impacting on

energy metabolism and body weight or directly by enhancing insulin sensitivity and glucose
uptake by peripheral tissues.65,66 Regular moderate intensity exercise performed over the second
and third trimesters of pregnancy can be used to attenuate important gestational diabetes mellitus
related adverse outcomes.67

vii. Delivery

With advancing gestation, the risk of macrosomia, shoulder dystocia and stillbirth are
increased in GDM. Management options include expectant management, induction of labour or
elective Caesarean delivery.17 There is no consensus on the timing of delivery as well-controlled
prospective studies are lacking.17 For the timing of delivery, the American Diabetic Association68

xxi
in 2004 recommended delivery at 38 weeks for women with Type 1 or Type 2 diabetes mellitus
predating pregnancy unless obstetric considerations dictated alternative management. The
National Institute for Clinical Excellence recommended that induction of labour can be offered
from 37 weeks to 38 weeks, 6 days, for women with type 1 or type 2 diabetes mellitus, however
those with uncomplicated gestational diabetes are advised to deliver no later than 40weeks plus 6
days.69 The Royal College of Obstetricians and Gynaecologists70 recommended induction of
labour at term to reduce the incidence of shoulder dystocia and fetal macrosomia. While the
mode of delivery for well controlled gestational diabetes remains uncertain, Caesarean section is
recommended only if estimated fetal weight is 4500grams or more.71

2.7. Perinatal Outcome

Gestational Diabetes is associated with increased rates of adverse maternal and neonatal
outcomes even in the mild forms.72 The proportion of adverse outcomes such as pre-eclampsia,
polyhydramnios, pre-term labour, obstetric interventions like labour induction and caesarean
deliveries is much higher compared with the general population. The same goes for fetal
complications such as fetal macrosomia and attendant complications of birth injuries, neonatal
hyperbilirubinemia, hypoglycemia, other metabolic imbalances and asphyxia.73

The purpose of screening and antenatal diagnosis is to enable obstetricians identify these group
of women and institute appropriate multi-disciplinary mode of management early enough to
prevent the onset of the complications highlighted above.74

xxii
 CHAPTER THREE

AIM AND OBJECTIVES

3.1 AIM: To determine the prevalence of Gestational Diabetes Mellitus and perinatal outcome
among women attending antenatal clinics.

3.2 SPECIFIC OBJECTIVES

1. To determine the plasma glucose levels among pregnant women attending antenatal clinic at
the University of Ilorin Teaching Hospital

2. Determine the prevalence of gestational diabetes mellitus among women at the antenatal clinic
of the University of Ilorin Teaching Hospital

3. Determine the risk factors present for gestational diabetes mellitus in the study population

4. To describe the perinatal outcome of women with gestational diabetes mellitus.

HYPOTHESIS

NULL HYPOTHESIS

1. The prevalence of GDM is not significant among women attending antenatal clinic at the
University of Ilorin Teaching Hospital

2. There are no significant differences in the risk factors of women with gestational diabetes
mellitus and women without gestational diabetes mellitus

3. The perinatal outcome in gestational diabetes mellitus is similar to outcomes in women with
normal blood glucose levels.
xxiii
ALTERNATIVE HYPOTHESIS

1. The prevalence of gestational diabetes mellitus is significant among women attending

antenatal clinic at the University of Ilorin teaching Hospital.

2. There are significant differences in the risk factors of women with gestational diabetes
mellitus and women without gestational diabetes mellitus.

3. The perinatal outcome in gestational diabetes mellitus is different from outcomes in

women with normal glucose levels.

xxiv
 JUSTIFICATION

Gestational diabetes mellitus is a major obstetric concern; it is gradually becoming a major

concern in the developing world which Nigeria belongs to. The majority of women with GDM
will revert to normal within six weeks post-partum. The disease may not be picked again in such
women until the subsequent pregnancy or later in life when it has progressed to overt diabetes
mellitus which occurs in about 50% of cases.

The attributed factors for GDM include an increase in the consumption of highly refined foods
and drinks containing refined sugars and sedentary lifestyle and obesity. These factors are also
increasing at an alarming rate in our society and it may increase the prevalence of GDM in our
society hence the need for improving the modalities for early detection. The new WHO
classification for GDM which provides a finer approach at detection and preventing the
occurrence of adverse perinatal and maternal outcomes has not been extensively studied in
Nigeria. This study aims to bridge the gap and also provide data for obstetricians to plan for
better management of this condition.

xxv
 CHAPTER FOUR

METHODOLOGY

4.1 BACKGROUND OF THE STUDY SITE

The study was carried out in the Department of Obstetrics and Gynaecology of the University of
Ilorin Teaching Hospital, Ilorin, and Kwara State, Nigeria. The recruitment of patients was done
at the Antenatal Clinic of the Department.

The University of Ilorin Teaching Hospital is located at Oke-Oyi, Old Jebba Road in
Ilorin. It predominantly plays the role of a teaching hospital but equally offers primary and
secondary health services. The hospital has about 2500-3000 deliveries per annum. It serves as a
major referral centre for Kwara State and parts of the nearby states of Oyo, Osun, Ekiti, Kogi and
Niger states.

The hospital is approved for and undertakes Undergraduate and Postgraduate Medical
Training. It is a training centre for Post Basic Nursing in Midwifery, Accident and Emergency
and Paediatric Nursing. It also has schools for Community Health Officers and Health
Information Management System. The hospital has facilities for the major clinical departments
i.e. Obstetrics and Gynaecology, Paediatrics, Surgery, Internal Medicine and clinical
laboratories.

The Obstetrics and Gynaeology Department is located in building 7 of the hospital

consisting of a two-storey building. On the ground floor is the Obstetric Emergency Ward which
also doubles as the Gynaecological Emergency Ward. The first floor houses a 25 bedded
postnatal surgical ward for those that had Caesarean delivery. The ultrasound and fetal

xxvi
assessment unit, obstetric theatre and neonatal intensive care unit are also on the first floor. The
second floor has the antenatal and postnatal medical wards; each ward has 30 beds.

The Obstetric unit is run by four firms; each firm consists of consultants, resident doctors
and house officers. The booking clinic is on Mondays while antenatal and postnatal clinics are
run concurrently from Tuesdays to Fridays by the different firms.

4.2 THE STUDY POPULATION

The subjects consisted of pregnant women between 24-28 weeks presenting for antenatal clinic
visits without a prior diagnosis of diabetes mellitus. Fasting plasma glucose was done after 24
weeks but before 28 weeks of gestation. The women were then classified into those with normal
blood glucose (N), gestational diabetes mellitus (GDM) and those with overt diabetes mellitus
(ODM), 18 based on the result of the blood glucose analysis. Those who had normoglycemia and
gestational diabetes mellitus18 had oral glucose tolerance testing done within a week of the
initial testing. When the women presented in labour, the antenatal records were reviewed and the
perinatal events was recorded in the proforma that has been earlier administered.

INCLUSION CRITERIA

Participants were consenting women in within 24-28 weeks with live intrauterine gestation
without previously diagnosed diabetes mellitus.

Women with singleton intrauterine gestation.

EXCLUSION CRITERIA

Non-consenting patients

Type II diabetes mellitus

Intrauterine fetal death

xxvii
Pregnancies with fetal congenital anomalies

Gestational age less than 24weeks

Gestational Age greater than 28 weeks

4.3 STUDY DESIGN

This study was a hospital-based prospective cross-sectional study. The subjects were pregnant
women presenting at the antenatal clinic between 24-28 weeks gestation with confirmed
singleton pregnancy.

4.3.1 SAMPLE SIZE DETERMINATION

The sample size was determined by the Fischer’s formula.75

N= Z2 P(1-P)

d2

N= minimum sample size for study

Z=standard normal deviation was set at 1.96 at 95% confidence interval

d= precision or degree of accuracy, was set at 0.03%

P= prevalence of GDM, for this study, a prevalence of 4.8% was used.8

P= 0.048

1-P= 1-0.048=0.952

xxviii
N= (1.962)(0.048)(0.952)

0.032

= 195

To cater for attrition, 10% of the sample size was added to the initial sample size.

Therefore, the minimum sample for this study was 215 women.

4.3.2 SAMPLING TECHNIQUE

The sampling technique was by purposive sampling method. The study involved consenting
pregnant women at gestational age of 24- 28 weeks who have satisfied the inclusion criteria.
They were recruited consecutively from the antenatal clinics till the sample size was complete.
Two hundred and fifteen women were recruited consecutively for the study.

4.3.3 RECRUITMENT OF PATIENTS

The recruitment of patients was at the antenatal clinics of the hospital. Eligible women who
satisfied the inclusion criteria were informed and counseled about the study in a language they
understood and informed consent was obtained. A study proforma was administered. The
proforma was designed to obtain their socio-demographic status and risk factors for Gestational
Diabetes Mellitus.(Appendix III). This included the bio-data, history of index pregnancy, past
obstetric, medical history and the family history.

The recruitment of patients for the study was done by the researcher and the research assistants.

A total of four research assistants were selected for the study and they were registrars from each
of the four firms in the department. They were trained before the commencement of the study on:
counseling of the potential participants, collection of information from the participants and they
also obtained blood samples from the patients whenever the researcher was not available.

xxix
4.4 SAMPLE COLLECTION

After a detailed explanation of the study was made to the participants and informed consent
obtained, questionnaires were filled, thereafter; they had a physical examination done, with
emphasis on weight, height and body mass index. The collection of samples was done by the
researcher and the research assistants.

The antecubital fossa was used, tourniquet was applied. Sterile surgical gloves were worn and
the site for venepuncture was disinfected with 70% alcohol. About 2ml of venous blood was
withdrawn, the tourniquet was removed, dry gauze was placed on the needle point and held in
place for about 20seconds to ensure homeostasis and the blood sample was put into a bottle
containing 5mg of fluoride oxalate and shaken gently to ensure complete mixing. The sample is
transported to the laboratory for storage and analysis thereafter.

At 24-28 weeks, the blood samples of the patients were taken for fasting plasma glucose. A value
of ≥7mmol/l was considered as overt diabetes and did not undergo oral glucose tolerance test.
Those with values < 7mmol/l were subjected to a repeat fasting plasma glucose and oral glucose
tolerance test using 75g of glucose solution in 300ml of water that taken over 5minutes, this was
done within a week of the initial fasting plasma glucose test. The amount of glucose given was
1.75g/kg of body weight up to total of 75grams which delivered 0.25grams of glucose per ml.
Two hours after the drink, a venous sample was withdrawn and put in a fluoride oxalate bottle
and taken again for analysis.

A diagnosis of gestational diabetes mellitus was made in those with fasting glucose levels greater
than 5.1mmol/l (92mg/dl) but less than 7mmo/l, or 2 hours post 75gram oral glucose load was
greater than or equals to 8.5mmol/l (153mg/dl).18 those with values within normal range were
diagnosed as normal.18

4.5 POST TEST EVALUATION

Following the blood glucose evaluation the consenting participants with normoglycaemia were
counseled on their results and advised to continue with the regular antenatal clinics till they are
term. They had fasting blood glucose repeated between 36-38 weeks to ensure that they are still
normoglycaemic.
xxx
Women with gestational diabetes mellitus were counseled on the need for a multi-disciplinary
approach to their management, the obstetrician, endocrinologists and dieticians were involved in
their management. They were counseled on diet, physical activity and medication for the
condition. Medication was commenced according to existing protocols for management.

The perinatal events were assessed by determining the gestational age at delivery, presence or
absence of preterm rupture of membranes, the duration of labour, mode of delivery and neonatal
outcomes.

Neonatal outcome were assessed by determining the first and fifth minute Apgar scores, birth
weight of the baby, need for neonatal intensive care unit admission and also any indication for
additional care beyond 24 hours at the neonatal intensive care unit.

4.6 FOLLOW UP OF PARTICIPANTS

The case notes of the participants were marked and their phone contacts taken for follow up

They were reviewed during the ante natal visits by the researcher and the assistants.

4.7 CHEMICAL ANALYSIS FOR DETERMINATION OF BLOOD GLUCOSE LEVELS.

The analysis was done using diagnostic kits manufactured by Agappe Diagnostics Switzerland
GmbH. It operates on the principle of glucose oxidation by glucose oxidase enzyme, which
catalyzed the oxidation of Beta D-glucose present in the plasma to glucono-1,5- lactone with the
formation of hydrogen peroxide;lactone is then slowly hydrolysed to D-gluconic acid. The
hydrogen peroxide is then broken down to oxygen and water by peroxidase enzyme. Oxygen
reacts with an oxygen acceptor such as ortho-toluidine which itself is converted to a colored
compound that can be measured colorimetrically.

xxxi
The chemical reaction is explained below;

Glucose + O2+ H2O →GOD Gluconic acid+ H2O2

2H2O2 + 4-Aminoophenazone + Phenol → POD 4H2O2 + Quinonimine

The reagent is composed of glucose(s.i.) R1 5×100ml/1×1000ml, Tris Buffer,(pH 7.40)

92mmol/l; phenol 0.3mmol/l; glucose oxidase 15000U/L; 4-aminophenazone 2.6mmol/L. The
reagent are sealed and stored at 2-80C in the refrigerator. The Glucose standard concentration is
100mg/dl.76,77

4.8 LABORATORY PROCEDURE

The laboratory analysis was carried out by the researcher, who was supervised by a Chemical
Pathologist. The samples collected were centrifuged at 1000rpm, the plasma was separated from
the red cells and the plasma is used for the chemical analysis. One thousand micro liter of
working reagent were put in into three different test-tubes, these test- tubes will be marked as
blank; standard and sample. To the test-tube containing standard solution was added ten micro
liter of Standard solution, while ten micro liter of the sample was added to the test-tube labeled
as ‘sample’. These were mixed and incubated for 10minutes at 370C. The absorbance of sample
and standard solutions were then measured against the reagent blank using the spectrophotometer
at a wavelength of 490-550nm.

The Glucose concentration will be measured using this formula;

Glucose concentration(mg/dl) Absorbance of sample × 100

Absorbance of standard

4.9 DATA ANALYSIS

The data were analyzed using the Statistical Package for Social Sciences software (SPSS)
version 21 and presented in frequency tables, pie chart, histogram etc. Chi-square analysis and
odds ratios with 95% confidence intervals were used to compare proportions and Samples t-test

xxxii
the difference between continuous data. Probability (p) values less than 0.05 were accepted as
statistically significant and Pearson’s correlation coefficient was used to determine the strength
of the relationship between the variables.

4.10 STRENGTH OF THE STUDY

The strength of the study rests on the methodology that was used, the samples size, the
laboratory analysis and standard reagents that were used. The study also used the new WHO
criteria18 which has not been tested in this center before.

CHAPTER FIVE

RESULTS

The study was conducted over a period of 7 months, from 2nd May to 31st November, 2016.

5.1 THE SOCIO-DEMOGRAPHIC AND OBSTETRIC VARIABLES.

Age: Table I: All the consenting women were within the reproductive age-group and the age
range was 20-42 years. The mean age was 29.62±4.62 years. Half of the study population
(50.2%) fell within the age bracket of 30-39 years, while 3.3% were within 40-44years.

Educational status: Most participants had tertiary education. One hundred and seventy one
(79.5%) women had tertiary level education. This is shown in Table I. The percentage of
women without any education was 0.9%, those with primary school level of education were
7(3.3%) and those with secondary school education were 35, accounting for 16.3%.

Ethnicity: Analysis of the ethnicity of the participants in Table I showed that they were
predominantly Yoruba. From Table I, 177 women (82.3%) were of Yoruba ethnicity. The other
ethnicities represented were Nupe(5.1%), Hausa/Fulani(1.4%), Igbo(6%), and Bariba(4.2%),
Igala(0.5%) and Ebira(0.5%).

Occupation: Majority of the subjects were traders accounting for 40 %( 86) of all the
participants followed by 37.2% (80) that were civil servants. The students accounted for 13.5%
while 9.3 %( 20) were unemployed .This is shown Table I. The participants were all between
social classes 1-4. Majority (122) were in the social class 3, these accounted for 56.7%.
xxxiii
Gravidity; The gravidity of the participants ranged between 1-7. Most of the participants(124)
had between 2-4 pregnancies, accounting for 57.7% of the population studied, 71(33%) were
primigravidas and 20(9.3%) had five or more pregnancies. This is highlighted in Table I.

Parity: There were 113(52.6%) women who were either para 1 or 2 while 102(47.4) women had
three or more parous experiences. This was shown in Table I, the table also shows the number of
children alive for the participants, 54.4 %( 107) women had ≤ 2 children alive, while 45.6 %( 98)
women had > 2 children alive.

Gestational age at time of recruitment: The gestational age at presentation ranged between 24-
28 weeks, and the Mean±SD was 25.57 ±1.19weeks.

The other clinical parameters obtained include; the body mass index, this ranged between 18.83-
48.57 kg/m2 . The mean±SD was 27.03±4.35 kg/m2. 28(13%) some of the women experienced
some illness during the pregnancy, the illnesses included, anemia, and hyper emesis gravidarum,
chronic hypertension in pregnancy, malaria and urinary tract infection. Malaria affected 19
women accounting for 67.9% of all those who were ill. Five women were hospitalized and
treated for anemia, hyper emesis gravid arum and malaria in pregnancy. Thirty-seven women
had glycosuria, accounting for17.2% of the participants.

5.2: PLASMA GLUCOSE LEVELS.

The plasma glucose levels of the participants are shown in Table II. The range of the initial
fasting plasma glucose done was 2.0mmol/l -6.10 mmol/l with a mean of 3.87± 0.70mmol/l.
During the conduct of the oral glucose tolerance test, the range of the fasting plasma glucose was
2.2-7.9mmol/l with a mean of 4.04 ±0.73mmol/l.Blood samples taken two hours after the
administration of the 75grams of glucose solution ranged between 3.4mmol/l -15.7mmol/l with a
mean of 5.78±1.65mmol/l. The repeat fasting plasma glucose conducted between 36-38weeks,
showed that the range of fasting plasma glucose was increased, the mean±SD was 4.31 ±
0.69mmol/l.Figure I. The gradual rise of the plasma glucose level as the gestational age
increased is highlighted by this graph.

5.3: PREVALENCE OF GESTATIONAL DIABETES MELLITUS STUDY

PARTICIPANTS AND RELATED FACTORS.
xxxiv
The prevalence as shown in the pie chart (Figure II) is 9% in this study. Out of the total
population of participants, 20(9%) had gestational diabetes mellitus, while 195 women were
normoglycaemic.

Table III; This shows the relationship between gestational diabetes mellitus and the
sociodemographic parameters of age, ethnicity and social class. It also compared gestational
diabetes Mellitus with gravidity. There was no statistical significance when all these parameters
were compared. P= 0.834, 0.888 and 0.189 respectively.

Table IV.There were 42(19.5%) women who had suffered at least a miscarriage in a previous
pregnancy, 3(1.4%) of those women had GDM in this study while 39(18.1%) of the women were
normoglycemic. Only 2 women had GDM in the previous pregnancy, however, they were
normoglycaemic in this study. Six (2.8%) women had babies with obvious congenital anomalies
in their previous pregnancies, while none had GDM in this pregnancy, five (2.3%) of the women
were normoglycaemic in this pregnancy, while 1(0.5%) participant had GDM. Fourteen women
(6.5%) had macrosomic babies in their previous pregnancies, the birth weight ranged between 4-
5.4kg, with a mean and standard deviation of 4.48±0.46kg. Two (1%) participants had babies
who sustained birth injuries in the previous pregnancies, and the 2 women were normoglycaemic
during this study.

Table V; Relationship between GDM and the index pregnancy. There was a statistically
significant relationship between gestational diabetes mellitus and glycosuria. p value was <
0.001. There were 37(17.2%) women who had glycosuria, out of this number, 12 women who
had gestational diabetes mellitus, while the others were normoglycaemic. Similarly, the body
mass index was also statistically significant, the mean BMI of women with GDM was
29.82±4.37kg/m2 and greater than the mean value of 26.74±4.25 kg/m2 in normoglycaemic
women ( p=0.002).

The relationship between GDM and family history. Thirty three women had mothers that have
diabetes mellitus, and thirty one participants had fathers who have diabetes mellitus. Three
women with maternal history of diabetes mellitus had GDM while 29 participants with mothers
xxxv
who had diabetes mellitus, were normoglycaemic. There was no statistical relationship between
maternal history of diabetes mellitus and occurrence of GDM in this study. ( χ2 =0.099Y).
Similarly the history of diabetes mellitus in the father when compared to the participants with
GDM was also not statistically significant. χ2 was 0.066Y.

The relationship between GDM and physical activity of the women also did not have any
statistical significance. 68(31.7%) women walked for less than 30minutes in a day, while 147
women walked for more than 30minutes in a day. were normoglycaemic. The findings also did
not have any predictive value for gestational diabetes mellitus.

Table VI; This shows that clinical parameters that correlated positively with GDM. These were
Age, BMI, Gravidity, Gestational age at delivery and Birth weight. They were assessed using the
Pearson correlation coefficient in relation to gestational diabetes in the participants, the
correlation ranged between 0.021-0.203. These showed that these parameters increased in
significance as they approached unity. The highest correlation was seen in the birth weight at
0.203 and body mass index, with a correlation of 0.193. However the body mass index and the
birth weight had statistical significance with p values of 0.005 and 0.003 respectively.

Table VII; Using multivariate logistic regression analysis of (<0.001), the odds ratio shows that
glycosuria can predict the onset of GDM 8times over absence of glycosuria (Odds ratio =8.351),
p<0.001. Although the body mass index was also a good predictor for GDM with Odds ratio of
1.112.

5.4: THE PERINATAL OUTCOME OF WOMEN WITH GESTATIONAL DIABETES

MELLITUS.

The participants all delivered between 31-42 weeks. There were 14(6.5%) deliveries before
38weeks gestational age while the remaining, 201 participants delivered at term accounting for
93.5%. The onset of labour was spontaneous in 193(89.8%) of the cases and 22(10.2%) had
induction of labour. Spontaneous vaginal delivery was achieved in 74.9% of women, 15(7%)
had instrumental vaginal delivery and 39(18.1%) had caesarean section. The birth weight ranged
between 1.7kg-4.9kg with a Mean±SD of 3.38±0.46kg. There were 29 macrosoomic babies born

xxxvi
to both normoglycemic women and women with GDM. The fifth minute Apgar score of ≥ 7 was
seen in 197(97.2%) of the babies born while those with Apgar scores of ≤6 were 18(8.4%).
There were two cases of intrauterine fetal deaths; both were preterm deliveries accounting for
0.9% of all the deliveries. Five babies sustained birth injuries, constituting 2.3%, and the various
injuries were 2 cases of humeral fractures, 1 case of Erb’s palsy and 2 cases of sub-conjuctival
haemorrhage.Thirty-seven(17.2%) of the neonates required NICU admission, and the duration of
admission ranged between 1-9 days. Those who stayed for less than 2 days were 13 and the
remaining, twenty-four stayed for more than 2days. The mean random blood glucose for the
marosomic babies was 3.63 ± 0.47mmol/l, and the range was 2.90 – 4.70mmol/l.

Table VIII: The mean birth weight of the babies who had gestational diabetes mellitus was
higher than those with normoglycaemia, this was significant p=0.003. The mean±SD birth
weight (in kilograms) seen in those who were normoglycemic was 3.34±0.44kg, compared with
those with GDM which was 3.71 ± 0.55kg. The mode of delivery had statistical significance,
more women with GDM had higher proportion of caesarean section(45%) compared with the
total number of delivery, unlike those who were normoglycaemic, caesarean section was done in
15.4%. P< 0.004.The NICU admission was also statistically significant (<0.001).

Figure III: Patients with GDM were managed by the various units within the department.
Thirteen patients used metformin for the management of their clinical conditions they accounted
for 65%, while the remaining (7) were managed on diet and exercise alone accounting for 35%.
They all had good glycaemic control during throughout the course of the pregnancy. There was
no difference in the perinatal outcome of those who were on medication and those who were not
on medication.

xxxvii
Table I: Socio-demographic Characteristics

Variables Frequency (N=215) Percent

Age(in years)
Range 20-42
Mean ±SD 29.62± 4.62
<25 29 13.5
25-29 71 33.0
30-34 83 38.6
35-39 25 11.6
40-44 7 3.3
≥45 0 0.0
Ethnicity
Yoruba 177 82.3
Nupe 11 5.1
Hausa/Fulani 3 1.4
Igbo 13 6.0
Bariba 9 4.2
Igala 1 0.5
Ebira 1 0.5
Educational status
None 2 0.9
Primary 7 3.3
Secondary 35 16.3
Tertiary 171 79.5
Social Class
Class 1 35 16.3
Class 2 43 20.0
Class 3 122 56.7
Class 4 15 7.0
Gravidity
xxxviii
 1 71 33.0
2–4 124 57.7
>4 20 9.3
Range 1–7
Parity (N=144)
Range 0–5
≤2 113 52.6
>2 102 47.4
Number of Children alive Range 0-4
≤2 107 54.4
>2 98 45.6

Table II: plasma glucose levels obtained at various gestational age.

Gestational age Test done Range Mean ± SD

< 24 weeks FPG (mmol/L) 2.00 – 6.10 3.87 ± 0.70

24 – 28 weeks FPG (mmol/L) 2.20 – 7.90 4.04 ± 0.73

2hrs PPG (mmol/L) 3.40 – 15.70 5.78 ± 1.65

36 – 38 weeks FPG (mmol/l) 2.90 – 6.80 4.31 ± 0.69

Linear trend: 9.175; p value: <0.001

Figure I: Trend of fasting plasma glucose

xxxix
 7

2
Initial_fasting FPG FPG_36_38weeks
Tests

Figure II: prevalence of Gestational Diabetes Mellitus

xl
xli
Table III: Relationship between GDM and Sociodemographic characteristics

Variables Blood Glucose χ2 p value

Normal Gestational Total
Blood Diabetes
Glucose Mellitus
n=195 (%) n=20 (%) N=215
Age Group
< 25 27 (13.8) 2 (10.0) 29 1.461Y 0.834
25 – 29 66 (33.8) 5 (25.0) 71
30 – 34 75 (38.5) 8 (40.0) 83
35 – 39 22 (11.3) 3 (15.0) 25
40 – 44 5 (2.6) 2 (10.0) 7
Ethnicity
Yoruba 160 (82.1) 17 (85.0) 177 1.141Y 0.888
Nupe 10 (5.1) 1 (5.0) 11
Hausa/Fulani 2 (1.0) 1 (5.0) 3
Igbo 13 (6.7) 0 (0.0) 13
Baruba 10 (5.1) 1 (5.0) 11
Social Class
Class 1 30 (15.4) 5 (25.0) 35 0.672Y 0.880
Class 2 39 (20.0) 4 (20.0) 43
Class 3 112 (57.4) 10 (50.0) 122
Class 4 14 (7.2) 1 (5.0) 15
Gravidity
1 68 (34.9) 3 (15.0) 71 3.328 0.189
2–4 109 (55.9) 15 (75.0) 124
>4 18 (9.2) 2 (10.0) 10
χ2: Chi square; Y: Yates Correction

xlii
 Table IV: GDM and Past Obstetric History

Variables Blood Glucose χ2 p value

Normal Gestational Total
Blood Diabetes
Glucose Mellitus
n=195 (%) n=20 (%) N=215
Miscarriages
Yes 39 (20.0) 3 (15.0) 42 0.058Y 0.809
No 156 (80.0) 17 (85.0) 173

No of Miscarriages (N=42)
1 27 (69.2) 3 (100.0) 30 1.095Y 0.578
2 10 (25.6) 0 (0.0) 10
3 2 (5.1) 0 (0.0) 2

DM in Previous Pregnancy
Yes 2 (1.0) 0 (0.0) 2 0.590Y 0.442
No 193 (99.0) 20 (100.0) 213

Fetal Anomaly
Yes 5 (2.6) 1 (5.0) 6 0.007Y 0.933
No 190 (97.4) 19 (95.0) 209

IUFD
Yes 9 (4.6) 3 (15.0) 12 2.003Y 0.157
No 186 (95.4) 17 (85.0) 203

Macrosomic baby
Yes 11 (5.6) 3 (15.0) 14 1.299Y 0.254
No 184 (94.4) 17 (85.0) 201

If Yes, Birth Weight in Kg

(N=14)
4.00 – 4.49 7 (63.6) 1 (33.3) 8 0.115Y 0.944
4.50 – 4.99 2 (18.2) 1 (33.3) 3
≥ 5.00 2 (18.2) 1 (33.3) 3
χ : Chi square; Y: Yates Correction
2 Macrosomia defined as ≥4kg

xliii
 Birth Injuries

Yes 2 (1.0) 0 (0.0) 2 0.590Y 0.442

No 193 (99.0) 20 (100.0) 213

Table V: Comparison of clinical presentations of normoglycaemic and GDM patients in index

pregnancy

Variables Blood Glucose t/χ2 p value

Normal Gestational Total
Blood Diabetes
Glucose Mellitus
n=195 (%) n=20 (%) N=215
Illness in Pregnancy
Yes 24 (12.3) 4 (20.0) 28 0.390Y 0.532
No 171 (87.7) 16 (80.0) 187
Hospital Admission
Yes 5 (2.6) 0 (0.0) 5 0.003 0.956
No 190 (97.4) 20 (100.0) 210
Glycosuria
Yes 25 (12.8) 12 (60.0) 37 25.125Y < 0.001*
No 170 (87.2) 8 (40.0) 178
BMI
Mean ± SD 26.74 ± 4.25 29.82 ± 4.37 215 -3.078t 0.002*
χ : Chi square; Y: Yates Correction; t: Independent Samples t-test; *: Statistically
2

Significant ( p value < 0.05)

Table VI: correlation between GDM and clinical characteristics

Variables R p value
Age 0.075 0.275
BMI 0.193 0.005*
Gravidity 0.067 0.330
GA at Delivery 0.021 0.755
Birth weight 0.203 0.003*

xliv
r: Pearson Correlation coefficient; *: Statistically significant ( p value < 0.05)

Table VII : Predictors of GDM using multivariate logistic regression analysis

Variable B Odds ratio (95% CI) p value

History of glucosuria 2.122 8.351 (3.039 – 22.949) <0.001*

BMI 0.106 1.112 (1.002 – 1.234) 0.047*

B: Coefficient of logistic regression; 95% CI: 95% Confidence interval; *: p value <0.05
Predictive value: 91.2%; R2: 0.237; Model χ2: 24.927; p value: <0.001

xlv
 Table VIII: Relationship between GDM and Perinatal Outcome

Variables Blood Glucose t/χ2 p value

Normal Gestational Total
Blood Diabetes
Glucose Mellitus
n=195 (%) n=20 (%) N=215
GA at Delivery(weeks)
Mean ± SD 38.91 ± 1.84 38.65 ± 1.66 215 0.608 0.544
28 – 36 11 (5.6) 3 (15.0) 14
37 – 42 184 (94.4) 17 (85.0) 201 1.299Y 0.254
Onset of labour
Spontaneous 176 (90.3) 17 (85.0) 193 0.123 0.726
Induced 19 (9.7) 3 (15.0) 22
Mode of Delivery
SVD 153 (78.5) 8 (40.0) 161 11.266Y 0.004*
Instrumental Delivery 12 (6.2) 3 (15.0) 15
Caesarean Section 30 (15.4) 9 (45.0) 39
Birth Weight(kg)
Mean ± SD 3.34 ± 0.44 3.71 ± 0.55 215 -3.387 0.001*
APGAR at 1st Minute
≤6 153 (78.5) 18 (90.0) 171 0.860Y 0.354
≥7 42 (21.5) 2 (10.0) 44
APGAR at 5th Minute
≤6 16 (8.2) 2 (10.0) 18 0.022Y 0.882
≥7 179 (91.8) 18 (90.0) 197
Neonatal Outcome
Alive 194 (99.99) 19 (99.9) 213 0.590Y 0.442
Dead 1 (0.01) 1 (0.1) 2
NICU Admission
Yes 27 (13.8) 10 (50.0) 37 14.201Y < 0.001*
xlvi
 No 168 (86.2) 10 (50.0) 178
Birth Injuries
Yes 3(1.5) 2 (10.0) 6 4.225 0.039*
No 192 (98.5) 18 (90.0) 209
Duration of NICU
Admission (N=37)
<2 7 (25.9) 6 (60.0) 13 2.373Y 0.123
≥2 20 (74.1) 4 (40.0) 24
χ : Chi square; Y: Yates Correction; *: Statistically Significant ( p value < 0.05)
2

Figure III; medication use for GDM.

Frequency

xlvii
 CHAPTER 6

DISCUSSION

Gestational diabetes mellitus is a well described disease affecting a significant population of

pregnant women worldwide. The diagnosis is challenging due to the of the absence of symptoms
and signs of disease, unlike overt diabetes mellitus which usually presents with established
clinical features. The presence of GDM predisposes the fetus to adverse perinatal outcomes, in
addition to maternal morbidities. While there are straightforward protocols for diagnosis of
diabetes mellitus in the general population, the diagnosis of GDM remains controversial.4,78 As
more women are at increasing risk of acquiring the disease, it is imperative to document the
trends in our environment, in order to better manage women in the antenatal period. This study
highlights the risk factors present in the antenatal population for GDM and their range of plasma
glucose. Two hundred and fifteen pregnant women who attended antenatal clinic at University of
Ilorin Teaching Hospital participated in the study, 20 women had gestational diabetes mellitus
based on the 2013 WHO criteria.18 The perinatal outcome of all the participants were described
in a bid to find relevant associations between these and gestational diabetes mellitus.

The prevalence of GDM in this study was 9%. This was within the range for gestational diabetes
mellitus obtainable in most part of the world. It is similar to findings in Aba, south-eastern
Nigeria.79 It is similar to the value obtained by Olarinoye et al in Ilorin, which was 11.6%80 as
well as the prevalence obtained by Anzaku AS in Jos, North central Nigeria.81 The prevalence
was however higher than 4.8% that was reported by Ewenighi et al in South Eastern Nigeria.8 In

xlviii
addition, a study done in UCH, Ibadan had a prevalence of 13.9%. 81 In South Africa, the
prevalence range is 1.8%-8.8%.83-86 The National prevalence of GDM in Australia is 8-10%.87
The figures from the Middle-East are considered quite high. A study in Medina by Alfadhli et al,
published a prevalence of 51%,88 a similarly high value of 24.9% was also published in UAE.89
The prevalence of gestational diabetes mellitus was within the range obtainable in this
environment for this study, this is in spite of the different criteria used in the diagnosis of
gestational diabetes mellitus. This study used the new WHO criteria which has not been adopted
by most centers.

The highest proportion of women in this study belonged to a range of 30-39 years, they
constituted half of all the participants (50.2%).Gestational Diabetes Mellitus has been observed
to increase with maternal age as demonstrated by Ewenighi et al in Ebonyi state where there
was a strong association between GDM an advancing maternal age.8 Though the age of the
participants wasn’t statistically significant, there was however a positive correlation when it was
analyzed using Pearson’s correlation coefficient, and it can still be used to predict the onset of
gestational diabetes mellitus. Almost 4/5th (79.5%) of all the women had a form of tertiary
education or another, this is an indicator that more and more women are delaying child-bearing
till later in life in order to acquire higher education. 90 The social class, occupation, gravidity and
parity all did not show any correlation and were not statistically significant even after Yates
correction. These factors however, have not been previously considered as risk factors for GDM.

The initial fasting plasma glucose and OGTT was done between 24-28 weeks, thereafter fasting
plasma glucose were taken at 36-38weeks. The Mean±SD(in mmol/l) for the initial test was
3.87mmol/l ± 0.70. while the repeat at 36-38 weeks was 4.31 ± 0.69. There was a rise in the
mean plasma glucose level late in the third trimester when compared to the values taken during
the late second-early third trimester. This was comparable to values obtained when plasma
glucose was assayed in pregnancy at similar gestational age.91

The chart also showed a rising trend as the gestational ages advanced up to term. This correlates
with the fact that insulin resistance increases with advancing gestation,1,2,79 thus women who are
at risk will benefit from monitoring of plasma glucose at this gestational age. Though no one
who was previously normoglycaemic was found out to have developed a new onset of
xlix
hyperglycemia. The range of the plasma glucose assay, taken 2 hours after ingesting 75gram of
glucose solution was 3.4mmol/l-15.7mmol/l. the Mean±SD was 5.78±1.65(mmol/l).

The presence of glycosuria was found to be significant, thirty-seven women had glycosuria,12
women with GDM had glycosuria, accounting for 60% of all the women with GDM, in the
normoglycaemic group however, 25 women had glycosuria, which accounted for 12.8% of those
with normoglycaemia and this was statistically significant (p<0.001). This finding shows that
glycosuria is still an important predictor of GDM, and women who have glycosuria should be
evaluated for GDM. This is in support of a study by van der Sande MAB et al in Gambia that
found a sensitivity of 64% for glycosuria in identifying diabetes mellitus, especially among
overweight, hypertensive and elderly subjects.92 Glycosuria has previously been demonstrated in
a study to be the most important indication for oral glucose tolerance test to diagnose gestational
diabetes mellitus.83 The analysis of the predictors of GDM using multivariate logistic regression
analysis, with 95% confidence interval showed that glycosuria was statistically significant
(p<0.001),and that glycosuria can predict the onset of GDM 8times over its absence(Odds
ratio=8.351). In a Sudanese study by MardiT.G and Lufti M.F, glycosuria was shown to have a
strong association with GDM,93 a similar finding was observed in a study in Iran 94
The use of
glycosuria should be utilized especially in low resource settings to improve ability to diagnose
GDM.

Body mass index was also found to be statistically significant when related with
GDM(p<0.002). The mean±SD for those with normoglycaemia was 26.74±4.25kg/m2 that of
those with GDM was 29.82 ± 4.37kg/m2, this finding has been observed in similar studies in
pregnant women in Nigeria, where BMI correlated positively with GDM.9,95 Insulinaemia due
to insulin resistance, especially in the obese has been found to worsen during pregnancy, this is
due to the production of anti-insulin hormones such as oestrogen, human placental lactogen and
progesterone.1,2,79,95 The body mass index may be a good predictor for GDM but this was not
significant on multivariate analysis(OR=1.112).

With the use of Pearson correlation coefficient, the correlation between blood glucose levels and
clinical variables of age, BMI, gravidity, gestational age at delivery and birth weight were
analyzed. Only birth weight and BMI were statistically significant at 0.003 and 0.005
l
respectively. The most significant correlation was seen with the birth weight, this was 0.203,
body mass index had a correlation of 0.193. the correlation of age, body mass index and
gestational age at delivery were 0.075, 0.067 and 0.021 respectively. Body mass index has been
found to correlate with GDM, the higher the body mass index, the higher the risk of GDM.

There was a significant relationship between GDM and measures of perinatal outcome.
Caesarean section accounted for 45% of all deliveries among those patients with GDM, whereas,
in those who had normoglycaemia, 15.4% had caesarean delivery. In contrast, vaginal delivery
was proportionally higher in those with normoglycaemia (78.5%) while 8(40%) of those who
had GDM delivered spontaneously (p=0.004). There is no evidence in support of elective
caesarean delivery in women with GDM except in the presence of an obstetric indication.70,71
The indications for caesarean deliveries in the participants with GDM were for obstetric reason,
such as fetal macrosomia. This finding was similar to what was obtained in a similar study in
where the proportion of those that had GDM and caesarean delivery was higher in comparison to
those with normoglycaemia.

The birth weight of the babies in women who had GDM was more than those with
normoglycaemia. The mean birth weight of babies of normoglycaemic women was 3.34±0.44kg;
this was lower than the mean birth weight of GDM mothers (3.71±0.55kg). The difference
obtained was statistically significant (p=0.001). The mean birth weight obtained did not qualify
to be described as macrosomia, but the obtained difference of 0.387kg was significant.
Similarly, there were no significant adverse perinatal outcomes related to birth weight in both
groups. This may be explained by the adequate management given antenatally and intra partum,
where all deliveries were supervised. Further studies to compare birth weight and perinatal
outcomes are required to determine any relationship.

The admissions into the NICU was statistically significant (p=0.001), the reasons for the
admissions were varied, 50 %( 10) of all the babies born to women with GDM needed
admissions in comparison with 13.8 %( 27) of those with normoglycaemia that needed NICU
admission. A similar finding has been observed in similar studies.96

li
The other parameters such as gestational age at delivery, mode, onset of labour, first and fifth
minute Apgar scores, neonatal outcome and duration of admission were not found to be
statistically significant.

CONCLUSION

The prevalence of gestational diabetes mellitus in this study was 9%. The clinical parameters of
glycosuria, mean birth weight, neonatal intensive care unit admission and body mass index were
statistically significant when they were related with gestational diabetes mellitus.

There was positive correlation between Age, body mass index, gravidity, birth weight and
gestational age at delivery and occurrence of GDM. The values of these parameters were higher
in the women with gestational diabetes mellitus than those who were normoglycemic and they
could serve as useful parameters in predicting the onset in pregnant women. Gestational diabetes
is associated with adverse perinatal outcomes, when the mode of delivery and NICU admissions
were considered. There was no difference in the outcome of those women with gestational
diabetes mellitus who used medication and those who were not on medication.

lii
 RECOMENDATIONS

1. Routine screening of women for gestational diabetes mellitus should be incorporated

into regular antenatal care programs.
2. There should be a replication of this study in multiple centers at the primary,
secondary and tertiary care levels, to help in determining a national prevalence for
gestational diabetes.
3. Separate screening and diagnosis of overt diabetes mellitus in the antenatal
population should be done to help reduce the complications associated with the
disease.
4. Patients with gestational diabetes mellitus and their babies should be followed up and
monitored to prevent the onset of Type II diabetes mellitus.
5. The use of glycosuria as a risk factor for Gestational Diabetes Mellitus is still valid in
our settings and pregnant women should have routine urinalysis done during the ante
natal period.
6. The body mass index should be calculated early during the antenatal
period,preferably in the first trimester or any time the women present for booking.
This can serve as a screening tool for GDM.
liii
 LIMITATIONS

1. There were very few studies done on gestational diabetes mellitus to compare with
2. There was a lack in the uniformity of the diagnostic criteria for glucose intolerance in
pregnancy.
3. Most of pregnant women do not come to the clinic fasting, this made it difficult to get
willing participants for the study
4. Post partum follow-up of mothers could not be done to determine blood sugar levels after
puerperium.
5. It was a hospital based study, conducted in a tertiary center, and most of the women in
the lower socio economic class prefer to attend the primary healthcare facilities rather
than teaching hospitals.
6. The role of interventions such as, exercise and diet on glucose levels in pregnancy could
not be evaluated.
7. The prepregnancy weight, body mass index and weight during the pregnancy gain during
the pregnancy could not be obtained in the women because they were not seen prior to
pregnancy and they were not seen in the first trimester.

liv
 REFERENCES

1. Saxena. R. Bedside Obstetrics and Gynaecology. Jaypee Brothers Med Pub. 2010;234-
239.
2. Murphy A, Carla J, Strehlow SL, Greenspoon JS, Palmer SM. Diabetes mellitus and
pregnancy . In: Decherney AH. Nathan L. Laufer N.Roman AS. (eds). Current Obstetrics
and Gynaecology: diagnosis and treatment. McGraw Hill, New York.11th. 2013;509-517.
3. Chukwunyere CF, Awonuga DO, Igwe U. Gestational Diabetes in a tertiary healthcare
centre at Abeokuta,south western Nigeria:A five year retrospective review.IJTDH,
2015;7(1):23-31.
4. World Health organization. 2012. Diabetes Factsheet No. 312.
5. O’Sullivan JB, Mahan CM. Criteria for the Oral glucose tolerance test in pregnancy.
Diabetes care.1964;13:278-285.
6. World Health Organization: Definition, Diagnosis and Classification of Diabetes mellitus
and it’s complications: Report of a WHO consultation. part 1:Diagnosis and classification
of Diabetes mellitus. Geneva, World Health Org.1999.

lv
7. Hunger-Dathe W, Volk K, Braun A, Sämann A,Müller UA, Peiker G . Perinatal
morbidity in women with undiagnosed gestational diabetes in northern Thuringia in
Germany. Exp Clin Endocrinol Diabetes 2005;113(3):160-166.
8. Ewenighi CO, Nwanjo HU, Dimkpa U, Onyeanusi JC,Nnatuanya IN,Onoh LUM.
Prevalence of gestational diabetes mellitus;risk factors among pregnant women(in
Abakaliki metropolis, Ebonyi state Nigeria). Nig J Integ Res Med 2013; 4(1):57-61.
9. John CO, Alegbeleye JO, Otoide AO. Foeto-maternal outcome of diabetes in a tertiary
facilty in Nigeria.AJDM.2015;23(2):13-16.
10. Chamberlain C, Banks E, Joshy G,Diouf I,Oats JJ,Gubhaju L et al. Prevalence of
gestational diabetes mellitus among indigenous women and comparison with non-
indigenous Australian women:1990-2009. Aust N Z Obstet Gynaecol. 2014;54(5):433-
440.
11. SOGC Clinical practice guidelines No.121. Screening for gestational mellitus. J Obstet
Gynecol Can 2002;24(11):894-903.
12. Adebisi SA, Oparinde DP, Olarinoye JK, Aboyeji AP,Ogunro PS. Gestatonal diabetes
mellitus; Diagnosis and Management. Postgraduate Doctor.2004;(2):1-6.
13. Anna V, van de Ploeg HP, Cheung NW, Huxley RR, Bauman AE. Sociodemographic
correlates of the increasing trend in prevalence of gestational diabetes mellitus in a large
population of women between 1995-2005. Diabetes Care. 2008;31(12):2288-2293.
14. Cheung K.W, Wong S.F. Gestational diabetes mellitus update and review of literature.
Reproductive sys sexual disord.2011.S2:002.doi:10.4172/2161-038X.S2-002
15. HAPO study cooperative research group. Hyperglycemia and adverse pregnancy
outcomes. New Engl J Med 2008;358(19):1991-2002.
16. Metzger BE International Association of diabetes and pregnancy study groups consensus
panel. International Association of diabetes and pregnancy study groups
recommendations on the diagnosis and classification of hyperglycemia in pregnancy.
Diabetes care.2010;33(3):676-682.
17. Coustan DR,Lowe LP,Metzger BE,Dyer AR. The hyperglycemia and adverse pregnancy
outcome (HAPO)study:Paving way for the new diagnostic criteria for gestational diabetes
mellitus Am J Obstet Gynecol. 2010;(202):654.e1-6.

lvi
18. World Health Organization. Diagnostic criteria and classification of hyperglycemia first
detected in pregnancy.WHO NMH MND 13.2 eng.Geneva:WHO.2013.
19. Catalano PM, McIntyre HD, Cruickshank KJ, McCance RD,Dyer AR, Metzger BE et al.
HAPO study. Associations of gestational diabetes mellitus and obesity with pregnancy
outcomes. Diabetes Care 2012;35(4):780-786.
20. Ferrerra A, Kahn H, Quesenberry C, Riley C, Hedderson M. An increase in the incidence
of gestational diabetes mellitus: Northern California. Obstet Gynecol.2004;103(3):526-
533.
21. Freinkel N. Maternal changes in pregnancy. In: Williams Textbook of Endocrinology.
J.D. Wilson and D.W. Foster (eds), Philadelphia, W.B. Saunders, 1985; 438-451.
22. Tutino GE,Tam WH, Yang X, Chan JC, Lao TT,Ma RC. Diabetes and pregnancy:
perspectives from Asia. Diabet Med. 2014;31(3):302-318.
23. Kaajo R, Rönnemaa T. Gestational Diabetes:Pathogenesis and consequences to mother
and offspring. Rev Diabet Stud. 2008;5:194-202.
24. Kautzky-Willer A, Parger R, Waldhausl W, Pacini G,Thomaseth K, Wagner OF et al.
Pronounced insulin resistance and inadequate beta-cell secretion characterize lean
gestational diabetes during and after pregnancy.Diabetes Care.1997;20:1717-1723.
25. Catalano PM, Huston L, Amini SB, Kalhan SC. Longitudinal changes in glucose
metabolism during pregnancy in obese women with normal glucose tolerance and
gestational diabetes. Am J Obstet Gynecol 1999. 180(4):903-916
26. Damm P, Vestergaad H, Kuhl C, Pederson O. Impaired insulin-stimulated non-oxidative
glucose metabolism in glucose-tolerant women with previous gestational diabetes. Am J
Obstet Gynecol 1996; 174(2):722-729.
27. Buchanan TA, Xiang AH, Gesational diabetes mellitus. J Clin Invest 2005;115(3):485-
491.
28. Colomiere M, Permezel M, Riley C, Desoye G, Lappas M. Defective insulin signaling in
placenta from pregnancies complicated by gestational diabetes mellitus. Eur J Endocrinol
2009; 160(4):567-568.
29. Sibai BM, Ross MG. Hypertension in gestational diabetes mellitus: pathophysiology and
long-term consequences. J Matern Fetal Neonat Med 2010;23(3):229-233.

lvii
30. Ogbera AO, Ekpebegh C. Diabetes mellitus in Nigeria: The past, present and future.
World Journal of Diabetes. 2014;5(6):905-911. doi:10.4239/wjd.v5.i6.905.
31. Wilkerson HLC, O'Sullivan JB. A study of glucose tolerance and screening criteria in
752 unselected pregnancies. Diabetes 1963;12:313- 318
32. Macafee CAJ, Beischer NA. The relative value of the standard indications for performing
an oral glucose tolerance test in pregnancy. Med J Aust 1974;(1): 911-914
33. Langer O, Rodriguez DA, Xenakis EMJ, McFarland MB Berkus MD, Arrendondo F.
Intensified versus conventional management of gestational diabetes. Am J Obstet
Gynecol 1994; 170(4): 1036 -1047.
34. Berkowitz GS, Lapinski RH, Wein R, Lee D. Race, Ethnicity and other risk factors for
gestational diabetes. Am J Epidemiol 1992; 135(9): 965-973.
35. Dornhorst A, Paterson CM, Nicholls JSD, Wadsworth J, Chiu DC, Elkeles RS, et al.
High prevalence of gestational diabetes in women from ethnic minority groups. Diabetic
Med 1992; 9: 820-825.
36. Roberts SB, Savage J, Coward WA, Chew B, Lucas A . Energy expenditure and intake in
infants bom to lean and overweight mothers. N Engl J Med 1988; 318(8):461-466.
37. Faren M,Daly N,O’Higgins CA, McKeating A, Maguire PJ, Turner MJ. The interplay
between maternal obesity and gestational diabetes mellitus. J Perinat Med
2015;43(3):311-317.
38. Zhang S, Folsom AR, Flack JM, Liu K. Body fat distribution before pregnancy and
gestational diabetes: findings from coronary artery risk development in young adults
(CARDIA) study. BMJ 1995; 311(7013): 1139-1140.
39. Branchtein L, Schmidt MI, Mengue SS, Reichelt AJ, Matos MC, Duncan BB. Waist
Circumference and Waist-to-Hip ratio are related to gestational glucose
tolerance.Diabetes Care 1997; 20(4): 509-511.
40. Carreno CA, Clifton RG, Huath JC, Myatt L, Roberts JM, Sponge JM et al. Excessive
weight gain and risk of gestational diabetes mellitus in nulliparous women. Obstet
Gynecol 2012.119(6):1227-1233.

lviii
41. Black HM, Sacks DA, Xiang AH, Lawrence JM. The relative contribution of
prepregnancy overweight and obesity, gestational weight gain and IADPSG-defined
gestational diabetes mellitus to fetal growth.Diabetes care.2013;36(1):56-62.
42. Mardi TG,Lufti MF. Risk factors for gestational diabetes mellitus in Sudanese pregnant
women. Int J Biomed Res 2012;1(1):79-84.
43. Mestman JH. Outcome of diabetes screening in pregnancy and perinatal morbidity in
infants of mothers with mild impairment in glucose tolerance. Diabetes Care
1980;3(3):447-452.

44. McCance DR, Pettitt DJ, Hanson RL, Jacobsson LTH, Knowler WC, Benneth PH. Birth
weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype, or
surviving small baby genotype? BMJ. 1994; 308(6934): 942-945.
45. Goud TG,Kumar PK,Ramesh K. Risk factors for gestational diabetes in Karnataka. Int J
Curr Res Aca Rev. 2014;2(9):286-291.
46. Philipson EH, Super DM. Gestational diabetes mellitus. Does it recur in subsequent
pregnancy ? Am J Obstet Gynecol 1989; 160(6): 1324-1331.
47. Gaudier FL, Hauth JC, Poist M, Corbett DL, Cliver S. Recurrence of gestational diabetes.
Obstet Gynecol 1992;80(5):755-758.
48. Tieu J,Crowther C, Middleton P. Dietary advice in pregnancy for preventing gestational
diabetes mellitus. Cochrane database of syst rev. 2008;16(2): CD006674.
49. Moses RG, Brand-Miller JC.Dietary risk factors for gestational diabetes mellitus, are
sweetened soft drinks culpable of guilty by association? Diabetes Care.
2009;32(12):3214-2315.
50. Tobias DK,Zhang C,van Dam RM, Bowers K Hu FB.. Physical activity before and
during pregnancy and risk of gestational diabetes mellitus. Diabetes Care.2011;34(1)223-
229.
51. Redden SL, LaMonte MJ,Freudenheim JL, Rudra CB. The association between
gestational diabetes mellitus and recreational physical activity. Matern child health J
2011;15(4):514-519.

lix
52. Van Poppel MN, Ruchar SM, Mottloa MF. Physical activity and gestational diabetes
mellitus. Med Sport Sci 2014;60:104-112.
53. Durak EP, Jovanovic-Peterson L, Peterson CM. Comparative evaluation of uterine
response to exercise on five aerobic machines. Am J Obstet Gynecol 1990;162(3): 754-
756.
54. World Health Organization. Diabetes Mellitus: Report of a WHO study group. Geneva,
World Health Org., 1985 (Tech. Rep. Ser. no. 727).
55. National Diabetes Data Group. Classification and Diagnosis of Diabetes Mellitus and
other Categories of Glucose Intolerance. Diabetes 1979; 28: 1039- 1057.
56. Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR et al.
Hyperglycemia and adverse pregnancy outcomes. New England Journal of Medicine
2008; 358(19):1991-2002.
57. Domhorst A, Nicholls JSD, Probst F, Paterson CM, Hollier K, Elkeles RS.Calorie
restriction for treatment of gestational diabetes. Diabetes 1991; 40 (2):161-164.
58. Parfitt VJ, Clark JDA, Turner GM, Hartog M. Maternal postprandial blood glucose levels
influence infant birth weight in diabetic pregnancy. Diabetes Res 1992; 19:133- 135.
59. American Diabetes Association Position Statement. Nutrition recommendations and
principles for people with diabetes mellitus. Diabetes Cure 1996; I(Supp1. 1): S16-S19
60. Hernandez TL,Van Pelt RE, Anderson MA, Daniels J. A higher complex carbohydrate
diet in gestational diabetes mellitus achieves glucose targets and lowers postprandial
lipids: a randomized crossover study. Diabetes care. 2014;37(5):1254-1262
61. Omoregie ES, Osagie AU. Glycemic indices and glycemic load of some Nigerian foods.
Pak J Nutrit 2008;7(5):710-716.
62. Canadian Diabetes Association. 1998 Clinical practice guidelines for the management of
diabetes in Canada. Can Med Assoc J 1998a; 159 (Suppl. 8): S19
63. Dhulkotia SJ, Ola B, Fraser R, Farrell T. Oral hypoglycemic agents vs insulin in
management of gestational diabetes: a systemic review and metaanalysis.Am J Obstet
Gynecol.2010;203(5):457.e1-459.e9

lx
64. Negrato CA, Zajdenverg L. self-monitoring of blood glucose during
pregnancy:indications and limitations. Diabet Metab Syn 2012,4:54 doi:10.1186/1758-
5996-4-54
65. Schulz LO, Weidensee RC. Non-insulin-dependent diabetes in Mexico. Prog Food Nutr
Sci 1993;17(2): 99-117.
66. Wake JA, Sowden JA, Storlein LH, James DE, Clark PW, Shine J et al. Effects of
exercise training and dietary manipulation on insulin regulatable glucose transporter
mRNA in rat muscle. Diabetes 1991;40(2): 275-279.
67. Barakat R, Pelaez M, Lopez C, Lucia A. Exercise during pregnancy and gestational
diabetes-related adverse effects:a randomized control trial. Br J Sports Med.
2013;47(10):630-636.
68. American diabetes association. S88-S90: 2004.Gestational diabetes mellitus. Diabetes
care.27(1);2004.
69. NICE Clinical guideline.NG3. Diabetes in pregnancy: management from preconception
to the postnatal period. NICE.2015.
70. Royal college of obstetricians and gynaecologist. Shoulder dystocia. Green top Guideline
42: 2012.
71. Rouse DJ, Owen J, Goldenberg RL, Cliver SP. The effectiveness and costs of elective
caesarean delivery for fetal macrosomia diagnosed by ultrasound. JAMA. 1996;
276:1480-1486
72. Gasim T. Gestational diabetes mellitus: Maternal and perinatal outcome in 220 Saudi
women. Oman Med J.2012;27(2):140-144.
73. Sendag F, Terek MC, Itil IM, Oztekin K, Bilgin O. Maternal and perinatal outcomes in
women with gestational diabetes as compared to nondiabeteic controls. J Reprod Med.
2001;46(12):1057-1062.
74. Casey BM, Lucas MJ, Mcintyre DD, Leveno KJ. Pregnancy outcomes in women with
gestational diabetes compared with general obstetric population. Obstet Gynecol
1997;90(6):869-873.
75. Araoye MO. Subjects selection. In: Research methodology with statistics for health and
social sciences. Ilorin: Nathadex Publishers. 2004;115-129.

lxi
76. Kanagasabapathy AS, Kumari S. Guidelines on standard operating procedures for clinical
chemistry.SEA-HLM-328.WHO.2000
77. Glucose(package insert).Cham,Zurich: Agappe Diagnostic, switzerland GmbH;2011.
78. Mpondo BCT, Ernest A, Dee HE. Gestational diabetes mellitus: challenges in diagnosis
and management.J Diab Metab Dis 2015.14(42).doi:10.1186/s40200-015-01697.
79. Nwaoguikpe RN, Uwakwe AA. Blood glucose levels of pregnant women at different
gestation periods in Aba area of Abia State of Nigeria. Sci Res Essays.2008;3(8):373-
375.
80.Olarinoye JK, Ohwovoriole AE, Ajayi GO. Diagnosis of gestational diabetes mellitus in
Nigerian pregnant women-comparison between 75G and 100G oral glucose tolerance
tests. West Afr j Med.2004;23(3)198-201.
81. Anzaku AS, Musa J. Prevalence and associated risk factors for gestational diabetes in Jos,
North-Central Nigeria. Arch Gynecol Obstet.2013;287(5):859-863.
82. Kuti MA, Abbiyesuku FM, Akinlade KS, Akinosun OM, Adedapo KS, Adeleye JO et al.
Oral glucose tolerance testing outcomes for among women at high risk for gestational
diabetes mellitus. J Clin Pathol.2011;64(8)718-721.
83. Mamabolo R, Alberts M, Levitt N, Delemarre-van de Waal H,Steyn N.Prevalence of
gestational diabetes mellitus and the effect of weight on measures of insulin secretion and
insulin resistance in third trimester pregnant rural women residing in the Central Region
of Limpopo Province, South Africa. Diabet Med.2007;24(3):233-239.
84. Jackson WPU, Coetzee EJ. Glycosuria as an indication for glucose tolerance testing
during pregnancy. S Afr Med J.1979;56.921-923.
85. Ranchod H,Vaughan J, Jarvis P. Incidence of gestational diabetes at Northdale
Hospital,Pietermaritzburg. S Afr Med J.1991;80(1):14-16.
86. Peer N, Steyn K, Lombard C, Lambert EV, Vythilingum B, Levitt NS. Rising diabetes
prevalence among urban-dwelling black South Africans.PLoS One. 2012;7(9):e43336.
87. Moses RG, Morris G, Petocz P,SanGil F, Garg D. Impact of the potential new diagnostic
criteria on the prevalence of gestational diabetes mellitus in Australia. Med J
Aust.2011;194:338-340.

lxii
88. Alfadhli EM, Osman EN, Basri TH, Mansuri NS, Youssef MH, Assaaedi SA et al.
Gestational diabetes among Saudi women: prevalence, risk factors and pregnancy
outcomes. Ann Saudi Med.2015;35(3):222.230.
89. Agarwal MM, Dhatt GS, Punnose J, Koster G. Gestational diabetes: dilemma caused by
multiple international diagnostic criteria. Diabet Med.2005;22:1731-1736.
90. Fagbamigbe AF, Idemudia ES. Survival analysis and prognostic factors of timing of first
childbirth among women in Nigeria. BMC Pregnancy and Childbirth.2016;16:102.
Doi:10.1186/s12884-016-0895-y
91. Hernandez TL, van Pelt RE, Friedman JE, Barbour LA. Patterns of glycemia in normal
pregnancy:should the current therapeutic targets be challenged? Diab Care.2011;34:1660-
1668.
92. van der Sande MAB, Walraven GEL, Bailey R, Rowley JTF, Banya WAS, Nyan OA. Is
there a role for glycosuria testing in sub-Saharan Africa? Trop Med Int
Health.1999;4(7):506-513.
93. Mardi TG, Lufti MF. Risk factors for gestational diabetes mellitus in Sudanese pregnant
women. Int J Med Biochem Res.2012;1(1):79-84.
94. Keshavarz M, Cheung NW, Babaee GR, Moghadam HK, Ajami ME, Shariati M.
Gestational Diabetes in Iran:incidence, risk factors and pregnancy outcomes. Diabetes
Res Clin Pract.2005;69:279-286.
95. Imoh LC, Ocheke AN. Correlation between maternal weight and insulin resistance in
second half of pregnancy. Niger Med J.2014;55(6):465-468.
96. Opara PI, Jaja T, Onubogu UC. Morbidity and mortality among infants of diabetic
mothers admitted into a special care baby unit in Port Harcourt, Nigeria.Ital J
Pediatr.2010;36(1):77.doi:10.1186/1824-7288-36-77

lxiii
 APPENDIX I

INFORMATION SHEET

STUDY TITLE : PATTERN OF BLOOD GLUCOSE AND PREGNANCY OUTCOME OF

WOMEN WITH GESTATIONAL DIABETES AT UNIVERSITY OF ILORIN TEACHING
HOSPITAL .

BRIEF DESCRIPTION OF THE STUDY

lxiv
 This study is in partial fulfillment of the requirements for Part II fellowship examination of the
Faculty of Obstetrics and Gynaecology of the National Postgraduate Medical College of
Nigeria.

High plasma glucose is associated with adverse outcome for the mother and the baby if not
properly managed. This study intends to identify this condition among women during this study
period, the risk factors present and to observe the perinatal events in these women.

WHAT IS REQUIRED FOR YOUR PARTICIPATION

You will be required to answer some questions and 2ml of your venous blood will be taken for
blood glucose analysis. If the initial test reveals diabetes mellitus, then you will require no
further testing, but if it does not you will be required to drink a glucose containing drink prepared
by the researcher, and 2ml of your blood will be taken again for blood glucose analysis

BENEFITS/RISK TO THE PARTICIPANTS

Participants in this study will have the opportunity to know their blood glucose levels. Those
with gestational diabetes mellitus and impaired glucose tolerance will be counseled and
recommended for appropriate management. The study will not expose you to any risk.

CONFIDENTIALITY

The information collected about you and result of your test will be made confidential.

COST OF RESEARCH/CONFLICT OF INTEREST

The researcher will bear all the cost in addition to an envisaged grant from the University of
Ilorin Teaching Hospital. No addition cost will be transferred to the participants. I have no
conflicts of interest.

CONSENT TO PARTICIPATE AND RIGHT TO WITHDRAW

lxv
Your participation in this study is voluntary and you have the liberty to withdraw from the study
at any stage if you so wish. This will neither attract any penalty nor affect the quality of care you
will receive.

RESEARCHER: DR AJIBOYE A.D[M.B.B.S ILORIN]

APPENDIX II

CONSENT FORM

lxvi
RESEARCH TOPIC: PATTERN OF BLOOD GLUCOSE AND PREGNANCY OUTCOME
OF WOMEN WITH GESTATIONAL DIABETES AT UNIVERSITY OF ILORIN
TEACHING HOSPITAL .

I………………………………………………………………………………………of…………
…………………………………………………………………………..

hereby consent to participate in the above research study after adequate explanation on the
nature, risks and benefits of the study have been made to me. I am also aware that I can withdraw
this consent anytime during the course of the study without any negative consequence.

Signature or Right thumb

print………………………………………………………………………………………

Date ………………………………………………………………………………………

I confirm that I have explained to you the purpose and nature of this study. All information
obtained in this study is confidential and if the study is published, there will be no information
that will identify you as a participant.

Signature………………………………………………………………………………….
Date…………………………………………………………………………………………..

Witness signature………………………………………………………………………..
Date………………………………………………………………………………………

APPENDIX III

INFORMATION DATA SHEET

lxvii
RESEARCH TOPIC: PATTERN OF BLOOD GLUCOSE AND PREGNANCY OUTCOME
OF WOMEN WITH GESTATIONAL DIABETES AT UNIVERSITY OF ILORIN
TEACHING HOSPITAL .

(a) SOCIODEMOGRAPHIC CHARACTERISTICS.

i. Serial number………….

ii. Hospital no…………….

iii. Age (years)………….

iv Occupation……………………………………..

vi. Educational status. None…..primary…..secondary……tertiary…..

vii. Ethnicity. Yoruba…..Nupe…..Fulani…….Ibo……Hausa…..Bariba..Ebira…Igala

(b) OBSTETRIC HISTORY.

i. Last menstrual period…………

ii.Gestational age…………………..

iii. Expected date of delivery……….

iv.Gravidity…………………

v. Parity…………… number of children alive

vi. Height……

vii. Weight……..

viii. Body mass index………..

(c). RISK FACTORS FOR GESTATIONAL DIABETES MELLITUS

lxviii
i. Diabetes mellitus in previous pregnancy[ies] Yes No

ii. History of fetal anomaly Yes No

iii. History of miscarriages Yes No

If yes, how many miscarriages…………….

iv. History of intrauterine fetal death Yes No

v. History of macrosomic babies Yes No

If yes, weight of baby………….

vi. History of birth injuries Yes No

If yes, nature of injury…………..

vii. History of hypertension in previous pregnancies Yes No

(d) HISTORY OF INDEX PREGNANCY

i. Have you been treated for any illness in this pregnancy? Yes No

If yes, nature of illness…………………

Were you admitted for any illness during this pregnancy? Yes No

If yes, nature of illness………………..

ii History of glycosuria Yes No

(e) LIFESTLYE OF PATIENT

i. Number of meals per day [1] [2] [3] [4] [5] [6] more

ii Intake of biscuits/pastries per week [1] [2] [3] [4] [5] [6] more

iii Number of sugar containing drinks per week [1] [2] [3] [4] [5] [6] more
lxix
 iv. Duration of walking per day; less than 30minutes

Greater than 30 minutes

(f) FAMILY HISTORY

i. History of diabetes mellitus in mother Yes No

ii. History of diabetes mellitus in father Yes No

(g) BLOOD GLUCOSE READINGS

i. Fasting plasma glucose……………………….(mmol/L)

ii. Fasting plasma glucose……(mmol/l);Oral glucose tolerance test……(mmol/L)…

iii. Fasting plasma glucose at 36-38weeks gestation…..(mmol/l)

(h) DELIVERY RECORD

i. Gestational Age at delivery……………….

ii. onset of labour…..Spontaneous Induction

iii. Mode of delivery.. spontaneous vaginal delivery operative delivery

cesarean section

(i) FETAL PARAMETERS AT DELIVERY

i. Apgar scores 1st Minute…………..5th minute…………….10th minute

iv. Birth weight…….grams

v. Neonatal outcomes….Alive, Deceased.

vi.Birth injuries Yes No

lxx
if yes, type of injury…………….

vii.Neonatal Intensive Care Unit Admission Yes No

viii.Indication for admission…….

ix.Duration of admission….

lxxi
lxxii