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Diabetes mellitus in pregnancy

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DOI: 10.4038/sljog.v37i2.7745

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Diabetes mellitus in pregnancy

Motha MBC Dias TD
INTRODUCTION
Diabetes mellitus in pregnancy Table 1 – GDM diagnostic threshold values from various organizations
could either be pregestational (pre-
existing ) or gestational. Gestational Plasma glucose concentration (mg/dl)
diabetes mellitus (GDM) is the most Organization OGTT Fasting 1 hour 2 hour 3 hour
common cause of diabetes during
glucose load
pregnancy, accounting for up to
90 % of pregnancies complicated ADA* 100g 95 180 155 140
by diabetes.1 Gestational diabetes ACOG* 100g 105 190 165 145
mellitus is defined as “any degree
NCE8 75g 100.8 140
of glucose intolerance with onset or
first recognition during pregnancy. 2 IADPSG8 75g 92 189 153
Marked variation in GDM prevalence DIPSI8
75g 140
among different racial/ethnic groups
has been documented, with higher *Diagnosis of GDM made if two or more glucose values equal to or exceeding the
prevalence among Native-American, threshold values. §Diagnosis of GDM if one or more glucose values equal to or exceeding
Asian, African-American, and the threshold values. OGTT: Oral Glucose Tolerance Test, ADA: American Diabetes
Hispanic populations than among Association, ACOG: American Council of Obstetricians and Gynecologists, NICE :
non-Hispanic whites. The prevalence National institute of clinical excellence, IADPSG: International Association of Diabetes
of gestational diabetes mellitus and Pregnancy Groups DIPSI: Diabetes in pregnancy study group India
is increasing reflecting the global
epidemic of obesity.3 In Sri Lanka, assessment for nephropathy by HAPO (The Hyperglycemia and
the prevalence of GDM was shown to estimating glomerular filtration rate Adverse Pregnancy Outcome) study
be 5.5% in a study carried out in Sri (eGFR) and urinary protein excretion which was a landmark multinational
Jayawardena general hospital while should be done prior to conception. study whose objective was to clarify
in another study done at the North The medications should be reviewed risks of adverse outcomes associated
Colombo teaching hospital, Ragama and modified to avoid teratogenic with degrees of maternal glucose
the prevalence of GDM was shown effects in the event of a pregnancy (eg: intolerance less severe than overt
to be 5.7% with the prevalence of angiotensin inhibitors/ angiotensin diabetes mellitus. 7 While the HAPO
both gestational and pregestational at receptor blockers/statins). Folic study demonstrated a positive
7.1%.4 5 acid 5 mg should be commenced linear relationship between screening
and continued throughout the first glucose values and adverse perinatal
trimester, while 75mg of aspirin outcomes it showed that blood
PRE-GESTATIONAL DIABETES should be commenced at 12 weeks of glucose values that were previously
MELLITUS gestation and continued until birth of considered ‘normal’ were associated
Preconception care forms the the baby. with adverse perinatal outcomes and
cornerstone of a successful pregnancy that the relationship of maternal
outcome in women with diabetes glucose to outcomes is a continuum.
SCREENING FOR GESTATIONAL The cut offs for gestational diabetes
preceding pregnancy. The aim of DIABETES MELLITUS
glycaemic management at this mellitus was based on the level of
stage is to attain a HbA1c <6.1%, There exists various guidelines for maternal blood glucose above which
without troublesome hypoglycaemic diagnosing GDM (Table 1). Urine key adverse outcomes (birth weight, C
symptoms. Screening for retinopathy glucose testing, fasting plasma glucose peptide levels and percent fetal body
by an ophthalmologist and and postprandial plasma glucose have fat >90th percentile) achieved an odds
been shown to have low sensitivity as ratio of 1.75 compared to mothers
screening tests for GDM and therefore with average glucose levels. The
Department of Obstetrics and Gynaecology, they are not recommended as recently published NICE guidelines
faculty of Medicine, University of Kelaniya, screening tests for gestational diabetes have lowered the cut off value for
Sri Lanka FBS to 100.8mg/dl, from the previous
mellitus6.
126mg/dl.8 (Table 1 ) The DIPSI
In March 2010, the International
Correspondence: Dr Motha MBC, recommends a glucose challenge test
Association of Diabetes and Pregnancy
with 75g of glucose taken any time
Senior Lecturer, Department of Obstetrics and Study Group (IADPSG) issued a
of the day (no need for fast) with an
Gynaecology, faculty of Medicine, University of consensus guidelines to potentially
Kelaniya, Sri Lanka. abnormal 2 hour post glucose blood
attain a single approach for GDM
sugar level considered significant.9
Email: cmotha6@gmail.com diagnosis based on the results of the

June 2015 Sri Lanka Journal of Obstetrics and Gynaecology 1

Leading Article www.slcog.lk/sljog

Universal screening for GDM is with pregestational diabetes mellitus Compared to diet alone, exercise
practiced in Sri Lanka with the 75g than in women with GDM.11 with dietary modifications has been
OGTT performed at 24-28 weeks found to lead to improved glycaemic
of pregnancy while screening for MANAGEMENT OF DIABETES control. 16 The proposed mechanism
pregestational diabetes is advocated MELLITUS IN PREGNANCY for such an improvement in glycaemic
at the booking visit in women not Benefits of treating gestational diabetes control is heightened sensitivity
known to have preexisting diabetes. mellitus has been demonstrated. The of peripheral tissues to insulin.
Australian Carbohydrate Intolerance Unfortunately, researchers have not
Study in Pregnant Women (ACHOIS), been able to suggest an evidence
PATHOPHYSIOLOGY OF GDM based intervention with guidelines
found reduced perinatal morbidity
Normal pregnancy is associated and mortality when standard for frequency, intensity, time and type
with a number of changes in glucose contemporary treatment of gestational of physical activity (FITT principle
metabolism. Data from the gold diabetes mellitus was compared for exercise prescription) that would
standard of assessment of insulin with no intervention, while more achieve good glycaemic control in
action, the euglycaemic glucose clamp recently the maternal fetal medicine women with GDM. Based on the
demonstrates that insulin action network (MFMU) study confirmed available evidence on the benefits of
reduces as pregnancy progresses due that treatment of GDM is beneficial exercise in managing GDM, ADA
to the insulin resistance created by in reducing macrosomia and large for recommends moderate exercise
certain hormones. Human placental gestational age babies. 12 13 programs for women without medical
lactogen and placental production of or obstetrical complications.17
tumour necrosis alpha (TNF-alpha) Dietary intake is fundamental to
optimal pregnancy outcomes because Pharmacological intervention in
appear to play a key role in the the management of GDM is usually
development of insulin resistance. nutritional quality and quantity
have an important impact on the employed when the woman fails
Pregnancy as an insulin resistant to meet established goals with
state may reveal even the smallest overall growth and development of
the fetus. Medical nutrition therapy conventional therapy of diet and
pre existing defects in insulin exercise. It is also indicated when
secretion or insulin sensitivity and as (MNT) is the cornerstone of managing
gestational diabetes. MNT has been elevated fasting glucose levels occur
a consequence, relative β-cell failure. while on conventional therapy,
The pathophysiological changes of defined as a ‘carbohydrate controlled
meal plan that promotes adequate because dietary modification alone
GDM are similar to those observed in has limited effect on fasting levels.
type 2 diabetes mellitus, which is also nutrition with appropriate weight
gain, normoglycemia, and the absence NICE recommends immediate
characterized by peripheral insulin treatment with insulin, with or
resistance accompanied by an insulin of ketosis.’ According to the ADA
recommendations, carbohydrate without metformin, as well as MNT, to
secretory defect. At the same time women with gestational diabetes who
there are changes in fasting glucose intake should be approximately 40 %
of total calorie intake and should be have a fasting plasma glucose level of
likely reflecting an increased uptake 126mg/dl or above at diagnosis while
of glucose by the fetoplacental unit, selected from foods with low glycaemic
index values.14 In pregnant women of in those with a FBS between 100.8-
with average fasting capillary glucose 126 mg/dl at diagnosis, addition of
readings low as 56mg/dl, found in normal body weight (BMI between
18–22.9 kg/m2), the recommendation pharmacological agents to MNT is
healthy, lean, normal glucose tolerant advocated when FBS remains above
women in the third trimester of is to consume 30–32 kcal/kg body
weight, especially during the second 126mg/dl following a two week trial
pregnancy.10 with MNT alone. 8
half of pregnancy.15 All women should
receive nutritional advice, preferably Prandial insulin and basal insulins are
ADVERSE EFFECTS OF DIABETES from an appropriately skilled the two main regimens used during
MELLITUS ON PREGNANCY dietitian. Advice on individualized pregnancy. Studies have shown that
plan for weight gain and caloric needs short acting insulin analogues (lispro
The adverse consequences of and determining protein, fat, and and aspart) are more effective than
gestational diabetes mellitus has been micronutrient needs should also be regular human insulin in achieving
known for some time but was clearly provided. target glucose values and minimizing
delineated by the HAPO study. the risk of macrosomia.18 19 Because
Macrosomia, neonatal hypoglycaemia, It is also imperative to note that only
20% of subjects in the ACHOIS trial the insulin analogues have shorter
caesarean section, shoulder dystocia, durations of action and more rapid
preeclampsia, preterm delivery, and 8% of Maternal fetal Medicine
Units Network subjects required onsets of action than regular insulin,
hyperbilirubinuria and admission to they are associated with improved
the neonatal intensive care unit was insulin, implying that lifestyle
modification and dietary intervention postprandial glycaemic control and
shown to be associated with maternal less postprandial hypoglycaemia.
hyperglycaemia. will be effective in 80–90% of women
with GDM. Due to limited data on the use of
Major maternal morbidity and basal analogues in pregnancy, NICE
mortality is more common in women recommends neutral protamine

2 Sri Lanka Journal of Obstetrics and Gynaecology June 2015

www.slcog.lk/sljog Leading Article

hagedorn (NPH) as the first choice had higher BMI in early pregnancy may be at risk of growth restriction
for long acting insulin during and higher baseline glucose levels.26 due to excessively tight maternal
pregnancy.20 The type of regimen Daily self monitoring of blood glucose control .31 A correlation has
and number of injections per day are glucose (fasting, premeal, postmeal been reported between ultrasound
determined based on the individual’s and bedtime at night), appears to be (USS) fetal abdominal circumference
needs and lifestyle. A basal bolus superior to intermittent monitoring of (AC) (AC>75th percentile) and high
insulin regimen (three bolus doses of plasma glucose as the hypoglycaemic amniotic fluid insulin levels in a
short acting insulin just prior to meals regimen could be tailored accordingly. recent study 30. There have been
with NPH insulin at night) or a split Consensus was reached at the fourth four randomized controlled studies
mixed dosage regimen (combination International workshop conference looking at the use of USS fetal AC as a
of short acting and intermediate acting on GDM on target capillary glucose guide to adjust the blood sugar levels.
insulin- Eg: Mixtard insulin twice values concentrations. Blood sugar
32 33 34 35
. Bonomo et al randomised 229
daily ) is used in pregnancy, though <95 mg/dl in the fasting state, <140 women to conventional treatment
the former regimen achieves better mg/dl at 1 hour, and <120 mg/dl 2 of GDM (glucose targets <90 mg/dl
glycaemic control.21 Pump therapy hours after starting the meal should (5.0 mmol/l) fasting and <120 mg/dl
(Continuous subcutaneous insulin be the treatment targets.27 In women (6.7 mmol/l) 2-hour post-prandial),
infusion- CSII) more closely mimics on insulin or glibenclamide, the or modified treatment targets based
physiological insulin secretion with blood sugar should not be allowed to on abdominal circumference on
evidence of less severe hypoglycaemia. drop below 72mg/dl.8 Urine glucose fetal ultrasound done two weekly as
CSII should be considered when monitoring is not useful though below. 35
adequate blood glucose control is not urine ketone monitoring can be • AC≥ 75th percentile: fasting< 80
obtained by multiple daily injections used in patients who are restricting mg/dl(4.4 mmol/l) and post-
of insulin without significant calories to detect insufficient caloric or prandial <100 mg/dl (5.5 mmol/l)
disabling hypoglycaemia. However, carbohydrate intake.28
benefits of CSII on glycaemic control • AC< 75th percentile: fasting< 100
during pregnancy have not been Although there is consensus about mg/dl(5.5 mmol/l) and post-
realized, with a Cochrane review postprandial glucose levels being prandial <140 mg/dl (7.8 mmol/l)
suggesting a potential increase in more important than preprandial They have reported a significant
infant birth weight associated with levels since the former correlates reduction in the percentage of LGA
CSII.22 The potential of a closed loop better with adverse neonatal events infants (7.9 vs. 17.9%), SGA infants
therapy, linking real time continuous such as fetal malformations, (6.0 vs. 9.0%), and macrosomia (3.3 vs.
glucose monitoring with insulin dose macrosomia, hypoglycaemia, and 11%) with this modified treatment. 35
adjustments to improve management shoulder dystocia, it has been debated USS fetal biometry may allow more
of diabetes during pregnancy is under as to whether glucose should be pragmatic treatment targets in some
investigation. measured one or two hours after a low risk patients, whilst tighter control
meal.29 Continuous blood glucose may be suggested for other patients
Metformin and glibenclanide are the monitoring using the continuous
two oral hypoglycaemics that can be at high risk of adverse perinatal
glucose monitoring system has outcomes.
used in pregnancy. Metformin can recently shown that glucose peaks
be used as an alternative or adjunct occur about 70 ± 13 minutes after a Fetal ultrasound assessment is
to insulin therapy. Metformin was meal in non diabetic pregnant women frequently used to estimate the fetal
shown to be similar to insulin with and after about 90 minutes in diabetic weight and wellbeing and to assist
regard to glycaemic control and women. safe prolongation of pregnancy and
neonatal outcome.23 Glibenclamide is time the date of delivery. However,
comparable to insulin in terms of birth Women with diabetes should have there is no uniform policy of frequency
outcome and glycaemic control and is contact with the joint diabetes and of USS examinations. Therefore, the
a suitable alternative to metformin.24 antenatal clinic for assessment of frequency of USS examinations should
NICE recommends glibenclamide for blood glucose control every 1–2 weeks be based on clinical indications. There
women with gestational diabetes in throughout pregnancy. is a paucity of high level evidence
whom blood glucose targets are not on the optimum gestational age for
achieved with metformin but who delivery in gestational diabetes.
TREATMENT ADJUSTMENT
decline insulin therapy or who cannot Different management strategies have
tolerate metformin. There is limited ACCORDING TO THE FETAL been adopted for pregestational or
evidence with regard to which oral BIOMETRIC PARAMETERS pre-existing diabetes. Rasmussen et al
hypoglycaemic should be selected. AND ANTENATAL FETAL noted that deaths in normally formed
Failure of glibenclamide was shown to infants occurred when there was
be higher in women with higher initial
SURVEILLANCE
clinical evidence of fetal macrosomia,
fasting glucose values above 115mg/ Despite optimum glycemic control polyhydramnios or poor metabolic
dl.25 Similarly for metformin, women there is a potential increase in the risk control. Consequently, uncomplicated
who required supplemental insulin of fetal macrosomia in women with GDM pregnancies could go up to 40
GDM.30 In contrast, some fetuses

June 2015 Sri Lanka Journal of Obstetrics and Gynaecology 3

Leading Article www.slcog.lk/sljog

Probability of shoulder dystocia by birth weight in diabetic and non-diabetic pregnancies37

Birth weight (g) Diabetic pregnancy Non-diabetic pregnancy
<4000 0.022 0.007
4000-4499 0.139 0.067
≥4500 0.525 0.145
completed weeks of gestation.36 active phase. Maternal hyperglycaemia hourly and an insulin infusion regimen
The potential risk of shoulder dystocia during labour increases the risk of commenced when two consecutive
is one of the major concerns in vaginal fetal hyperinsulinaemia and thus blood sugar readings are above
delivery in women with gestational hypoglycaemia and fetal acidaemia. 126 mg/dl, with insulin adjusted
diabetes. Although increasing fetal Therefore maternal blood sugar according to an insulin infusion scale.
weight is positively associated with surveillance should be continued Intravenous dextrose and insulin
the risk of shoulder dystocia, as many during labour with hourly monitoring infusion should be considered for
cases occur in instances where birth of blood sugar, in women who have women with type 1 diabetes from
weight is less than 4000 g. Rouse et al been on insulin or oral hypoglycaemics the onset of established labour. The
reported the probability of shoulder during pregnancy. infusion scale should consider both the
dystocia by birth weight in diabetic Women should have their normal diet insulin requirement in late pregnancy
and non-diabetic pregnancies37. and continue their insulin regimen and the blood glucose level. (Table 2)
Royal College of Obstetricians and until active labour begins. Women A syringe pump is set up with 50
Gynaecologists has recommended to on long acting basal insulin should U of soluble insulin in 50 ml of
offer an elective Cesarean delivery in continue this, while short acting and normal saline, while a 5% dextrose
case of estimated fetal weight >4500g intermediate acting insulin should solution containing 20 mmol/L of
in diabetic mothers. be discontinued at the time of active potassium chloride is commenced at
labour. The aim is to maintain blood 100ml per hour. If two consecutive
glucose between 70 and 126 mg/dl blood sugar readings are above 162
DIABETIC KETOACIDOSIS during labor irrespective of whether mg/dl, the infusion rate should
the women has type 1 or type 2 be shifted one column to the right
In pregnancy, diabetic ketoacidosis
diabetes or GDM.8 A maternal blood and if two consecutive readings are
(DKA) can occur at a relatively
glucose value of more than 180 mg/ below 72 mg/dl , the infusion rate
lower blood glucose level due to
dl has been conclusively proven to be should be shifted one column to the
physiological changes that accompany
associated with high risk of neonatal left. Following delivery the infusion
pregnancy. Emesis and the tendency
hypoglycemia. 38 The protocols for should be reduced to the lowest scale
for early lipolysis following relatively
use of insulin during pregnancy are and blood sugar monitored hourly
short episodes of fasting (‘accelerated
mostly based on studies in type 1 until the woman resumes her normal
starvation of pregnancy’), result in
diabetes mellitus patients. meals.
ketonuria being found in a significant
number of healthy pregnant During labour, normoglycemia is The infusion regimen can be adopted
women. Therefore, for a diagnosis mostly achieved with rapid acting for women undergoing a caesarean
of DKA in pregnancy, ketonaemia insulin when indicated, so as to section too, which should be
or academia (pH < 7.3 or serum prevent hypoglycemia in the neonate. performed in the morning hours.
bicarbonate < 15mmol/L ) should be Blood glucose should be monitored
demonstrated. DKA is associated with Table 2- Insulin infusion regimen for women during active labour 39
poor uteroplacental blood flow and
fetal acidosis, which is reflected on Current total Up to 40 41-60 61-90 > 91 units/day
cardiotocography. As fetal acidosis daliy insulin units/day units/day units/day
reverses with satisfactory treatment dose
of DKA, emergency delivery should Capillary Infusion rate Infusion rate Infusion rate Infusion rate
not be planned in the presence of an Glucose
abnormal CTG in this setting. DKA (units / hr) (units / hr) (units / hr) (units / hr)
(mg/Dl)
is a medical emergency and should
0-54 0 0 0 0
be managed in intensive care setting.
The management is similar to that of a 55-125 1.0 1.5 2.0 2.0
non-pregnant adult with DKA. 126-160 1.5 2.0 3.0 4.0
INTRAPARTUM MANAGEMENT 161-195 2.0 3.0 4.0 5.0
The insulin requirement during the 196-270 3.0 4.0 5.0 6.0
latent phase remains at a stable level >270 Exclude diabetic Exclude diabetic Exclude diabetic Exclude diabetic
though it may increase during the ketoacidosis ketoacidosis ketoacidosis ketoacidosis

4 Sri Lanka Journal of Obstetrics and Gynaecology June 2015

www.slcog.lk/sljog Leading Article

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6 Sri Lanka Journal of Obstetrics and Gynaecology June 2015

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