Diabetes and pregnancy

1. Gestational Diabetes
MJ Rasaee
TMU ,Tehran
2022

2. 1- Type 1 diabetes, formerly called juvenile diabetes, is usually
first diagnosed in children, teenagers, or young adults. In this
form of diabetes, the beta cells of the pancreas no longer make
insulin because the body's immune system has attacked and
destroyed them.
2-Type 2 diabetes, formerly called adult-onset diabetes, is the
most common form. People can develop it at any age, even
during childhood. This form of diabetes usually begins with
insulin resistance, a condition in which muscle, liver, and fat
cells do not use insulin properly. At first, the pancreas keeps up
with the added demand by producing more insulin. In time,
however, it loses the ability to secrete enough insulin in
response to meals.
IDDM 10%(die if no insulin),NIDDM 90%(insulin resistance)
1. is a brown to black, poorly defined, velvety
hyperpigmentation of the skin. It is usually found in
body folds
2. It typically occurs in individuals younger than age
40, may be genetically inherited, and is associated
with obesity or endocrinopathies, such as
hypothyroidism or hyperthyroidism, acromegaly,
polycystic ovary disease, insulin-resistant diabetes,
or Cushing's disease.
3. Acanthosis nigricans may also be seen with certain
medications that lead to elevated insulin levels (e.g.,
glucocorticoids, niacin, insulin, oral contraceptives,
and protease inhibitors)

3. Long term complications of diabetes (problem with micro- and macro vessels)
1. Diabetic eye(Cataracts and glaucoma, microaneurisms ).
"proliferative retinopathy". haemorrhage in the eye can lead
to blindness. New-grown fragile vessels
2. Diabetic feet
3. Diabetic kidney(30-50% of Diab patients develop kidney
disease) proteinuria
4. Diabetic heart(coronary artery disease risk 4 times
greater)
5. Chronic hyperglycemia causes increased glycation of
proteins, resulting in Advanced Glycation Endproducts
(AGEs)
6. Diabetic ketoacidosis: body uses fat as an energy source
and this results in the production of ketones that
accumulate in the body. Seen in type I DM .Infection, fever, beta
– agonists are frequent predisposing factors .Suspected with +serum
ketones and blood glucose levels above 300Fetal distress is common
7. thirst, passing large volumes of urine, feeling very tired,
nausea, vomiting and abdominal pain
13 000 new cases in children each year (USA)
CA: cancer, CF:
cystic fibrosis,
MS: multiple
sclerosis, JRA:
juvenile
rheumatoid
arthritis, MD:
muscle dystrophy

4. Insulin could be obtained from cows’ or pigs’ pancreases (used since 1922).(7-10 lb
pancreatic tissue per patient per year)Bovine insulin = 3 amino acid differences
,Porcine insulin = 1 amino acid difference .Amino acid differences stimulate allergic
responses .Human insulin also cause formation of antibodies in substantial number of
users (55%) lipoatrophy.Nevertheless human insulin is preferred .Human gene library
was screened and INS gene subcloned into a plasmid expression vector using lac
operon to promote transcription 24 aa Signal peptide leader was added to 5’ end.
secretion of insulin into culture medium instead of its retention inside inclusion
bodies(Signal leader detaches as insulin is transported across cell membrane..) A chain
synthesized in one E. coli strain .B chain synthesized in a different E. coli strain .Chains
are purified separately then joined together .Continuous culture techniques used
Expression in E. coli resulted in inclusion bodies packed full of insulin .Isolation of
insulin from inclusion bodies is timely and expensive
Humilin (Eli Lilly, 1986) – first industrially
produced human insulin
Contains a signal sequence + A,B, C sections of protein, Signal
sequence is removed after targeting to RER,Translation
continues on RER (forming proinsulin) ,Removal of 33 amino
acids at Golgi ,and S-S joining of A and B chains to form insulin

5. 5-Gestational diabetes is a condition in which a woman
without diabetes develops high blood sugar levels during
pregnancy. Although this form of diabetes usually goes
away after the baby is born, a woman who has had it is more
likely to develop type 2 diabetes later in life. Gestational
diabetes is caused by the hormones of pregnancy or by a
shortage of insulin. Out of every 100 women in the United
States, three to eight get gestational diabetes . Prevalence in
Canada:3.5 - 3.8% non-Aboriginal (but multi-ethnic)
population, 8.0 - 18.0% Aboriginal.Gestational diabetes
generally results in few symptoms in most women,
gestational diabetes causes no symptoms. Some women do
get symptoms of high blood sugar, such as increased thirst,
increased need to pass water and increased hunger however,
it does increase the risk of pre-eclampsia, depression, and
requiring a Caesarean section. Babies born to mothers with
poorly treated gestational diabetes are at increased risk of
being too large, having low blood sugar after birth, and
jaundice. If untreated, it can also result in a stillbirth. Long
term, children are at higher risk of being overweight and
developing type 2 diabetes, although these are also common
later on in pregnancy anyway.
3-In pre-diabetes, blood glucose levels are higher
than normal but not high enough to be
characterized as diabetes. However, many people
with pre-diabetes develop type 2 diabetes within
10 years. Pre-diabetes also increases the risk of
heart disease and stroke. With modest weight
loss and moderate physical activity, people with
pre-diabetes can delay or prevent type 2
diabetes.
4-Pre-gestational diabetes .Insulin dependent
.Non-insulin dependent (uncommon)
< 8.0 ?

6. Although there is no clear reason why some
women get gestational diabetes, women are
more at risk if they:have a family history of
type II (adult-onset) diabetes
are over the age of 35 are obese
have previously given birth to a large baby
have previously given birth to a baby born
with an abnormality ,have previously had a
stillbirth late in pregnancy

7. Gestational Diabetes Mellitus (GDM)
Prior “selective screening” resulted in missed
cases:
◦ Caucassians < 25 y.o.
◦ No personal or FHx of DM
◦ No prior infant with birth weight > 4 kg
Treatment of GDM reduces prenatal morbidity
Diagnosis GDM   maternal anxiety ?
◦ Evidence controversial for this
Therefore all women should be screened
have previously had a stillbirth late in pregnancy
* Presence of multiple risk factors warrants earlier
screening (preconception, 1st & 2nd trimester)
Causes fetal hyperglycemia Leading to fetal
hyperinsulinaemia,Fetal hyperinsulinaemia - even short
periods (1-2hours) lead to detrimental consequences in:
fetal growth ,fetal well-being
Maternal Hyperglycemia

8. ‫داری‬ ‫بار‬ ‫پیشرفت‬ ‫با‬ ‫انسولین‬ ‫تولید‬ ‫افزایش‬
‫انسولین‬ ‫تولید‬ ‫بر‬ ‫داری‬ ‫بار‬ ‫اثر‬ ‫با‬ ‫استرویید‬ ‫اثر‬ ‫مقایسه‬

9. G - ADAPTATION TO PREGNANCY
In early pregnancy Estrogen and Progesterone stimulate beta cell hyperplasia and increased insulin secretion
.Glycogenolyis and peripheral utilization increase .The net result is relative hypoglycemia of mother

11. Oral Glucose ToleranceTest (OGTT)
for pre-diabetics
Research has shown that the OGTT is
more sensitive than the FPG test for
diagnosing pre-diabetes, but it is less
convenient to administer. The OGTT
requires to fast for at least 8 hours before
the test. plasma glucose is measured
immediately before and 2 hours after
drinking a liquid containing 75 grams of
glucose dissolved in water. blood glucose
level is between 140 and 199 mg/dL 2
hours after drinking the liquid a form of
pre-diabetes called impaired glucose
tolerance or IGT, meaning that one is
more likely to develop type 2 diabetes
but do not have it yet. A 2-hour glucose
level of 200 mg/dL or above, confirmed
by repeating the test on another day,
means that have diabetes

12. Fetal Hyperinsulinaemia
1. Promotes storage of excess nutrients - macrosomnia
2. Increased catabolism of excess nutrients - energy usage
and  fetal oxygen storage
3. Episodic fetal hypoxia catecholamines causing: -
hypertension,cardiac remodelling and hypertrophy,
Erythropoietin, RBC’s, haematocrit causing poor
circulation and hyperbilirubinaemia
4. Induction of labor for “impending” fetal macrosomia
does not reduce the rate of either injury and may
increase the rate of cesarean .Planned cesarean is
reasonable (in diabetics) with EFW > 4250 g.
5. Good to fair evidence that screening with therapy
reduces the rate of fetal macrosomia .Insufficient
evidence that screening reduces the rate of cesarean,
birth injury or neonatal morbidity and mortality)
.Screening produces many false positives Agrees that
screening with 50 g CHO with 3 hour GTT as follow-up
is acceptable

13. CHO METABOLISM 20- 24 WEEKS
Increased human placental lactogen – diabetogenic
Increased prolactin – insulin resistance
Increased cortisol – decreased glycogen storage
Stable amounts of FFA
Increased cholesterol and TG
Reduced amino acid levels
NEONATAL METABOLIC COMPLICATIONS
Hypoglycemia
Hypocalcemia
Hypothermia
Hypomagnesemia
Hyperbilirubinemia
Fetal cardiac anomalies may be complex
CNS – Spina Bifida, Anencephaly
Caudal regression syndrome
Must consider family history of other malformations that
are unrelated to DM
Nerve injury:Rate varies from 4-40% following shoulder
dystocia
Most (90%) resolve without sequelae .Can occur with
EFW < 4000 g .Can occur in utero and therefore not
preventable by cesarean
Polycythemia and hyperviscosity
Neonatal hypoglycemia
Neonatal hypocalcemia
Hyperbilirubinaemia
Hypertrophic and congestive cardiomyopathy
RDS
Childhood impaired glucose tolerance
Miscarriage
IUGR
Macrosomia
Birth Injury
Morbidity and Mortality

14. Polycytemia (defination .occurance and pathophysiology)
1. Polycythemia is increased total RBC mass ,Central venous hematocrit >
65% . Above 65% blood viscosity rises exponentially.
2. Polycythemic hyperviscosity is increased viscosity of the blood resulting
from increased numbers of RBCs .Not all polycythemic infants have
symptoms of hyperviscosity .Polycythemia occurs in 2-4% of newborns
.Half of these are symptomatic .Hyperviscosity occurs in 25% of infants
with hematocrit 60-64% .Hyperviscosity without polycythmia occurs in
1% (nonpolycythemic hyperviscosity
Clinical signs result from regional effects of hyperviscosity and from the
formation of microthrombi .Tissue hypoxia , Acidosis ,Hypoglycemia
Organs affected: CNS, kidneys, adrenals, cardiopulmonary system, GI tract
Enhanced fetal erythropoiesis usually related to fetal hypoxia
◦ Placental insufficiency
◦ Maternal hypertension, abruption, post-dates, IUGR, maternal
smoking
◦ Endocrine disorders: due to increased oxygen consumption
◦ IDM (>40% incidence), congenital thyrotoxicosis, CAH, Beckwith-
Wiedemann syndrome (hyperinsulinism)
Increased risk of GI disorders and NEC with
partial exchange transfusion (PET)
Older trials show decreased neurologic
complications from hyperviscosity with PET, but
newer trials show no real benefit
PET is controversial!
Infants with asymptomatic polycythemia have an
increased risk for neurologic sequelae
Normocythemic controls with the same
perinatal history have a similarly increased
risk

15. Effects on the baby after birth
The baby may have low blood sugar (hypoglycaemia) after birth. This is because the baby's pancreas
makes extra insulin in response to the mother's high blood sugar levels. Shortly after birth, the baby
may continue to make extra insulin even though high levels of blood sugar are no longer present. After
a pregnancy affected by gestational diabetes, the newborn baby's blood sugar level is checked regularly.
Sometimes babies are given an early feed of a sugar (glucose) solution through a drip (fed directly into
a vein) to correct low blood sugar.
It is more likely that the newborn baby will develop jaundice . This is not serious and usually fades over
a few weeks, without the need for medical treatment being born very large and with extra fat; this can
make delivery difficult and more dangerous for baby low blood glucose right after birth breathing
problems.There is an increased risk that the baby will be born with congenital problems, such as a heart
defect. Sometimes, infants can be born with respiratory distress syndrome, in which the baby has
problems breathing because his or her lungs have not matured as normal. This usually clears up with
time. There is also a slightly higher chance of stillbirth or death as a newborn, but if detected and the
glucose levels well managed, death is rare. There may be an increased risk of the baby developing type
II diabetes or being overweight later in life. Hypoglycemia ,Hypocalcemia , Hypothermia
,Hypomagnesemia ,Hyperbilirubinemia. Neonatal metabolic complications
Maternal Fetal/Neonatal
Macrosomia
(birth trauma, cesarian)
Macrosomia
(shoulder dystocia)
Preeclampsia RDS
Polyhydramnios Neonatal hypoglycemia
Prenatal mortality (fetus) Neonatal hypocalcemia
Postpartum IFG, IGT, DM
3-6 mos: 16-20 %
Lifetime: 30-50 %
Neonatal jaundice
Obesity later in life?
IGT, IFG, or DM later in
life?
• All women of reproductive age should consume
at least 0.4 mg of folic acid. High risk women
should consume 4 mg/day. This reduces the risk
of neural tube defects. Newer evidence suggests
a lower risk of facial clefting and congenital
heart disease as well
• Macrosomia:(Greater than 90 precentile, 4200
grammes) ,Increased hyperbilirubinaemia
Increased hypoglycemia ,Increased acidosis
Increased birth trauma ,Macrosomnia as a child and
glucose intolerance in adulthood
1.3 3.1 38
145
300
0
50
100
150
200
250
300
Cases
per
100,000
1890 1920 1935 1973 2005
Year
Childhood Diabetes

16. Gestational Diabetes management
Pre-conceptional care
1-Tight glucose control (HbA1c):Aim for HbA1c < 6.1%.Strongly
advise against if HbA1c > 10.0 %
2-Assessment and treatment of associated medical problems -
hypertension, renal, retinal and/or heart disease
3-Folic acid:5 mg/day until 12 weeks gestation
4-Assessment of family. Financial and personal resources to help
achieve a successful pregnancy
5-Educate and empower (hypos, risks, need for structured care etc.)
6-Avoid unplanned pregnancy
7-Retinopathy assessment
8-Dietetic input, advice re obesity
9-Insulin if necessary (Hypoglycemic agents?)
10-weekly visits to Diabetic service/antenatal service & Growth
Monitoring (scan)
11-Delivery based on obstetric issues
12-Delivery gestation depends on insulin usage
1. “Tight” periconceptual control is essential
2. The diabetes should be stable
3. Multidisciplinary team maybe helpful
4. Diabetic education
5. Dietary counseling
6. Assessment of renal function
7. Retinal exam
8. FBS and 2 hour post-prandial levels
9. Pre-meal values if sliding scale short acting insulin coverage
is used
10. Early AM value if hypoglycemia suspected
11. Assure that reflectance meter is calibrated
12. Fasting blood glucose < 100 mg/dl
13. Pre-meal levels <110 mg/dl
14. Post-meal levels <140 – 150 mg/dl
15. Avoid wide swings in control
16. Normalize hemoglobin A1C

17. Maternal Complications
Chronic hypertension:Should be aggressively controlled.ACE inhibitors are
contraindicated.Calcium channel blockers are probably a reasonable alternative and are
safe during pregnancy.Increases the incidence of fetal growth restriction and
superimposed preeclampsia
Pre-eclampsia: BP > 140/90 .Proteinuria > 300 mg/24 hours or increase in baseline
.May be difficult to diagnose in the presence of renal disease and chronic HTN .25%
incidence of superimposed disease with CHTN. Lab: elevated LFT’s.
thrombocytopenia.Sxs: headache, epigastric pain, blurred vision
Oliguria, pulmonary edema, fetal growth restriction
Diabetic ketoacidosis ,Maternal hypoglycemia ,Maternal trauma ,Higher C Section rate
Retinal disease/renal disease not affected significantly by pregnancy: Remains the
leading cause of blindness in women ages 24-64 .Every patient with pre-gestational
diabetes should have a retinal examination in early pregnancy .Laser therapy is safe
and effective during pregnancy .Has a variable course during pregnancy
Nephropathy :Accounts for 1/3 of the deaths in diabetics < 31 .Renal findings are
present as early as 1-2 years after diagnosis
Creatinine clearance may improve in pregnancy due to increased renal blood flow
.Proteinuria may increase substantially. Pregnancy is possible even in patients
requiring hemodialysis .Reliable contraception is advised .Fertility and successful
pregnancy outcomes are reduced with serum Cr > 2.0
Spontaneous abortions:In well controlled patients the rate is similar to the non-diabetic
Higher rates of spontaneous abortion in diabetics with vascular disease

18. GDMTreatment
CBG qid: FBS, 1-2h pc
Dietary: 3 small meals, 3 small snacks
If glycemic targets not met: Insulin
◦ Multiple Daily Injection (MDI) best
◦ Insulin: regular, lispro, aspart ? (still new)
◦ No glargine (stimulates IGF-I receptors)
No OHA’s, not standard of care yet.
Glyburide
◦ Minimal crossing of placenta, 3rd trimester most
organogenesis complete
◦ 1 RCT: 404 women, mild GDM, glyburide vs.
insulin, no difference in outcomes
◦ Further study before safety established
Metformin
◦ Retrospective cohort:
◦  preeclampsia & stillbirth
◦ Bias: DM women older, more obese
NPO during Labour:
Monitor CBG q1h, target BS 4 – 6.5 mM
Hypoglycemia (BS < 4 mM): IV D5W
Hyperglycemia (BS > 6.5 mM): IV D5W & IV insulin gtt
Postpartum:
D/C all insulin (IV and SC)
CBG in recovery:
> 10 mM  CBG qid, may need Rx for T2DM
< 10 mM  stop CBG monitoring
FBS or 2hPG in 75g OGTT within 6 mos postpartum and prior to any
future planned pregnancies
Encourage: breast feeding, healthy diet, exercise to prevent future Type
2 DM, GDM
Screen for future T2DM (GDM is a risk factor)
GDM: Labour & Postpartum

19. T1DM, T2DM & Pregnancy
Congenital anomalies: 2-3x increased risk
◦ Cardiac malformations
◦ Neural Tube Defects 1 % risk
Folate 1-4 mg/d (Prenatal vitamin 0.4-1.0 mg)
d/c ACE-I and ARBs  methyldopa, etc.
Dilated eye exam: preconception & 1st trimester
T2DM: d/c OHA  insulin
Good glycemic control prior to conception:
◦ Prevent unplanned pregnancies: OCP or 2x barrier
◦ Initiate MDI and qid (FBS, 2hPC) prior to preg
◦ CSII also another option
T1DM & T2DM: Labour & Postpartum
NPO during Labor:
Monitor CBG q1h, target BS 4.0 – 6.5 mM
IV D5W & IV insulin gtt (Hamilton Health
Sciences Protocol)
Postpartum:
D/C all IV insulin
Insulin resistance/requirements rapidly fall
during & after labor
T2DM: monitor CBG qid
Restart insulin if CBG > 10 mM
T1DM: postpartum honeymoon
CBG q1h x 4h, then q2h x 4h, then
q4h
Restart MDI insulin S.C. when
CBG > 10 mM
No OHA, ACE-I or ARB during breast
feeding!

21. Clinical presentation
Symptoms are non-specific!
CNS: lethargy, hyperirritability, proximal muscle hypotonia,
vasomotor instability, vomiting, seizures, cerebral infarction
(rare)
Cardiopulmonary: respiratory distress, tachycardia, CHF,
pulmonary hypertension
GI: feeding intolerance, sometimes NEC
GU: oliguria, ARF, renal vein thrombosis, priapism
Metabolic: hypo-glycemia/-calcemia/-magnesemia
Heme: hyperbili, thrombocytopenia
Skin: ruddiness
ALWAYS draw a central venous sample if the capillary hematocrit
is > 65% .Warmed capillary hematrocrit > 65% only suggestive of
polycythemia
Diagnosis
Serum glucose
Hypoglycemia is common with polycythemia
Serum bilirubin
Increased bili due to increased RBC turnover
Serum sodium, BUN, urine specific gravity
Usually high if baby is deyhdrated
Blood gas to rule-out inadequate oxygenation as cause of
symptoms
Platelets, as thyrombocytopenia can be present
Serum calcium b/c hypocalcemia can be seen
Other labs to check

22. DETECTION OF FETAL MALFORMATIONS
HBA1C at first visit
1st trimester ultrasound for dating and to exclude anencephaly
Targeted USN at 16 – 20 weeks
Triple or Quad screen at 16 weeks
Fetal echocardiogram at 20 –22 weeks

23. FIRST PRENATAL VISIT
Routine prenatal lab
Baseline 24 hour UA for protein and Cr Clearance
Baseline retinal exam
EKG
Thyroid function tests in Type 1 Diabetics
Hemoglobin A1C
Schedule 10-12 week USN

24. GLYCOSYLATED HGB AND MALFORMATIONS
HBA1C <8.5% , 3.4% malformations
HBA1C > 8.5% , 22.4 % malformations
Reflects glucose control over the preceding 60 – 90 days
Glycosylated albumen reflects more recent level of control
Not as well studied in pregnancy

25. INDICATIONSFOR
HOSPITALIZATION
Persistent nausea and vomiting
Significant maternal infection
DKA
Poor control/compliance
Preterm labor
Well controlled IDDM: at term
Poorly controlled: after documentation of fetal
lung maturity
If fetal surveillance reassuring, delivery before
39 weeks should be unusual
TIMING OF DELIVERY
No breakfast the morning of induction
Establish IV with D5/.45% NaCl at 125 cc/hour
Capillary blood glucose levels every 1 – 2 hours
Begin continuous infusion of insulin with levels
above 120 mg/dl
Avoid fluid boluses with D5
INTRAPARTUM GLUCOSE CONTROL

26. POSTPARTUM GLUCOSE CONTROL
Insulin requirements may fall 50% in the 1st 24 hours
If C/S most will not require insulin until POD 1 or 2
Monitor QID CBG’s
Little need for treatment if under 200 mg/dl

27. CONTRAINDICATIONS IN DM
Over age 35
Hypertension
Retinopathy
Vascular disease
Nephropathy

28. ACOG Low Risk
Age < 25
Not a member of an at risk ethnic group (Hispanic, African, Native American, South or East
Asian, Pacific Islanders)
BMI < 25 (non-obese)
No history of abnormal glucose tolerance or FH
No adverse outcomes

29. 2 hour, 75 g CHO
FBS and every 30 minute blood glucose levels x 4
IF FBS > 140 or 2 of the post-prandial blood sugars > 199 = Diabetes
Impaired glucose tolerance if FBS between 115 and 139 or one PP value > 199

30. Normal Maternal Glucose Regulation
Tendency for maternal hypoglycemia between meals - fetal demand
Increasing tissue insulin resistance during pregnancy  diabetogenic placental
steroid
 Oestrogen, Progesterone,
 Chorionic sommatomammotrophin
Increased insulin production (= 30% mean)

31. Congenital Anomalies
Cardiac defects x18 8.5%
CNS defects x16 5.3%
◦ Anencephaly x 13
◦ Spina Bifida x 20
All Anomalies x 8 18.4%
Background major defects 1-2%

32. Congenital Anomalies and Diabetic Control
Maternal HbA1c levels
< 7.2 Nil
7.2-9.1 14%
9.2-11.1 23%
> 11.2 25%
Critical periods - 3-6 weeks post conception
Need pre-conceptional metabolic care

33. Glucose Challenge Test
Non fasting
50g glucose dose
Value > 7.8mmol/l - needs a OGTT
10-15% need a OGTT
20-40% have GDM (2-7% of pop screened)
(Risk factor screening fails to detect 43% of GDM)

34. Management
Multidisciplinary approach
Antenatal visits - 2-weekly after 24 weeks
Diabetic service 2-weekly
Scans - Anomaly scan at 20-weeks
Growth scans from 26-28
weeks
Delivery - around term if insulin dependent
unless complications, diet only control as
normal antenatal patients
Intrapartum management
IV fluids (5% dextrose) + KCl+ insulin
Hourly glucose monitoring
CTG
Manage labor as normal

35. Management - Postpartum
Use pre pregnancy insulin levels
when on diet and monitor. If GDM
monitor sugars only
Breast feeding v Bottle feeding?
GDM - OGTT at 6 weeks
GDM - long term risk of NIDDM
Contraception
Most groups agree that post-partum screening is
advised and that annual assessment is ideal
The best method is controversial but the data
favors a 2 hour, post 75 g CHO approach

36. HYDRAMNIOS
1-2 % in normals and 18% of diabetics
Fetal osmotic diuresis is etiologic
May also be due to fetal cardiac CNS malformations
May be associated with preterm labor
Associated with level of glycemic control