Have tried to include ADA and ACOG latest update

1. Diabetes Mellitus in
Pregnancy
Anupam Ghimire
GP/EM Resident

2. Contents
• Introduction
• Epidemiology
• Screening and Diagnosis
• Complication and its pathogenesis
• Management

3. Introduction
• Most common medical complication during
pregnancy
• Major cause of perinatal morbidity & mortality
• Excellent glycemic control-improves perinatal
outcome
• Goal-not only to improve perinatal outcome but
also to prevent long term maternal & fetal
effects

4. Incidence
• Abnormal maternal glucose regulation : 3-10%
• varies acc. to ethnicity, selection criteria and diagnostic
test
• Asians: 5-8%
• DM in pregnancy
– GDM- 87.5%
– Type I DM-7.5%
– Type II DM-5% (NICE 2008)
• >50% of GDM patients- develop type 2DM
(Obstet Gynecol 2003;101:380-92)

5. Etiologic classification of diabetes mellitus
I. Type 1 diabetes( insulin dependent DM)
A. Immune mediated
B. Idiopathic
II. Type 2 diabetes( Non insulin dependent DM)
III. Other specific types
-Genetic defects of ß-cell function
-Genetic defects in insulin action
-Diseases of the exocrine pancreas
-Endocrinopathies
-Drug- or chemical-induced
IV. Gestational diabetes mellitus (GDM)

6. Carbohydrate Metabolism
• Diabetogenic condition
• Progressive insulin resistance
- Anti-insulin action
- Insulin destruction : kidney, placenta
• Increased Lipolysis
- Mother utilises FA for caloric need
• Change in gluconeogenesis
- Alanine , major gluconeogenic source

7. • Early pregnancy  Increased insulin
sensitivity  Risk of hypoglycemia
• Mid second and Third trimester  Increased
insulin resistance  GDM

8. PREGESTATIONAL DIABETES
Criteria for diagnosis
1.Symptoms of diabetes plus random plasma glucose
concentration ≥ 200 mg/dl (11.1 mmol/l) OR
2. FPG ≥126 mg/dl (7.0 mmol/l) OR
3. 2-h post load glucose≥ 200 mg/dl (11.1 mmol/l) during
OGTT (WHO 75 g glucose)
criteria should be confirmed by repeat testing on a
different day.

9. Gestational diabetes mellitus
• “Any degree of glucose intolerance that either
commences or is first diagnosed in pregnancy
’’
- Includes whose glucose tolerance will return
back to normal after pregnancy
- Who persist with glucose intolerance and
develop type 2 diabetes
(ACOG)

10. Risk factor for GDM
• Obesity ( >15% of non pregnant
ideal body weight)
• Positive family history of diabetes
(sibling or parent)
• Persistent glycosuria
• H/o of diabetes in previous
pregnancy
• H/o stillbirth or unexplained
neonatal death
• ≥3 abortions in Ι or ΙΙ trimester
• H/o delivery of large infant (>4
kg)
• H/o traumatic delivery with
neurological disorder in infant
• H/o congenital anomaly in
prev baby
• H/o preeclampsia
• Chronic hypertension
• Recurrent severe moniliasis
• Recurrent UTI
• Polyhydramnios
• Diagnosis of PCOS

11. Screening
• Whom to screen?
• Method of screening?
• Time (POG) of screening?
• Advantages and disadvantages of screening
and selected method

12. Whom to screen
• ACOG and WHO –
– universal screening at 24-28 weeks
– high risk women- screening at fist antenatal visit
• ADA - risk factor analysis
-OGTT if indicated

13. Universal vs selective screening-
Asian scenario
• Prevalence of GDM- 16.55%
(Seshiah V et al.J Assoc Physians India 2004)
• Prevalence of GDM in rural Nepal)– 6.6%
( Thapa P et al , JNHRC, 2015)
• Universal screening
– More sensitive
– Missing GDM -adverse long term effects
Universal screening is preferred over selective screening

14. Screening methods
• Blood tests
– Random blood glucose (RBG)
– Fasting blood glucose (FBG)
– 1-hr 50 gm glucose challenge test (GCT)
– 2 hr 50 gm glucose challenge test
– 75 gm glucose tolerance test
– Fructosamine
– Glycosylated hemoglobin
• Urinary test
– Glycosuria

15. Glucose challenge test
• world wide accepted
50g glucose load regardless of meals
140mg/dl 130mg/dl
Sensitivity 79% 90%
specificity 87%
Need for GTT 14-18% 20-25%
With 140mg/dl as cut-off - good reproducibility
If 1hr -140mg/dl: OGTT is warranted
If 200mg/dl - GDM :no further testing
(ADA 2008)

16. • Hyperglycemia and Adverse Pregnancy Outcome
(HAPO) study , a large-scale multinational cohort
study completed by more than 23,000 pregnant
women:
- demonstrated that risk of adverse maternal, fetal,
and neonatal outcomes continuously increased as a
function of maternal glycemia at 24–28 weeks of
gestation, even within ranges previously considered
normal for pregnancy
- For most complications,there was no threshold for
risk.

17. • These results have led to careful reconsideration of
the diagnostic criteria for GDM.
• GDM diagnosis can be accomplished with either of
two strategies:
1. “One-step”
2. “Two-step”

18. One step diagnosis of GDM
• WHO – 75 g OGTT
• useful in populations with high prevalence of GDM
• Does not requires 50g GCT
• The diagnosis of GDM is made when any of the following plasma
glucose values are met or exceeded:
- Fasting: 92 mg/dL (5.1 mmol/L)
- 1 h: 180 mg/dL (10.0 mmol/L)
- 2 h: 153 mg/dL (8.5 mmol/L)

19. One step diagnosis of GDM
• Advantages over 100gOGTT
– Single step method
– More sensitive
– Cheap , convenient for the patients
– Does not need 50g GCT
• Disadvantages
– Over diagnosis

20. Two-step strategy
• Step 1: 50-g GCT (nonfasting),with plasma glucose
measurement at 1 h, at 24–28 weeks of gestation in women
not previously diagnosed with overt diabetes.
- If the plasma glucose level measured 1 h after the load is
>130mg/dL, 135mg/dL, or 140mg/dL (7.2mmol/L, 7.5mmol/L,
or 7.8mmol/L), proceed to a 100-g OGTT
• Step 2: 100-g OGTT should be performed when the patient is
fasting.

21. Diagnosis of GDM
Glucose
load
Thresholds (mg/dl) (venous plasma)
Fasting 1-h 2-hr 3hr
ADA
100g
(Carp & C)
≥95 ≥ 180 ≥ 155 ≥ 140
75g ≥ 95 ≥ 180 ≥ 155
ACOG
(NDDG)
100g ≥ 105 ≥ 190 ≥ 165 ≥ 145
WHO 75g ≥ 126 ≥ 140

22. COMPLICATIONS
Obstetric
– Congenital anomalies
– Spontaneous abortion
– Polyhydroamnios
– Preterm delivery
– Macrosomia
– Unexplained fetal death
– Pre-eclampsia
– IUGR
– Traumatic delivery
Medical
– Retinopathy
– Nephropathy
– Diabetic keto-
acidosis
– Hypertension
– Hypoglycemia
– Neuropathy
– Infections

23. Congenital anomalies
• Cardiovascular
– TGA, VSD, ASD
• CNS
– Acrania, anencephaly, NTDs, microcephaly
• Skeletal system
– Hemivertibra, CAUDAL REGRESSION SYNDROME
• Renal
– Renal agenesis, ureter duplication, hydronephrosis
• Gastrointestinal-duodenal atresia,small left colon
syndrome
• HbA1c levels vs risk of anomalies
– 6%- 3%
– 15%- >40%

24. • Macrosomia : Birth wt : >4.0 kg in diabetic
>4.5 kg in non-diabetic
AJOG 2000;182:1489-95
• Complications
– Maternal
• injuries to the birth canal
• increased risk of LSCS -30%
(Jensen et al.Diabetes Med 2010)
– Fetal
• Intrapartum asphyxia
• birth trauma (e.g. clavicular fractures)
• shoulder dystocia
• brachial plexus injury
• fetal death (0.4%)
Macrosomia/LGA

25. Pathogenesis -Pederson hypothesis
↓↓

26. Still birth
• Causes
– Poor glycemic control - decreased uteroplacental blood flow
- fetal hypoxia & acidosis
– Fetal hyperinsulinemia - ↑ O2 requirement
– Placental vasculopathy
– Maternal ketacidosis-20-50%
– Electrolyte disturbances
– Fetal hypertrophic cardiomyopathy
Still births within 72 hrs of seemingly normal FHR have
been reported
(Girz BA et al. J Perinatol 1992;12:229-33)
Perinatal mortality in Pregestational DM
• 10-50%-due to congenital anomalies

27. Management
• Prepregnancy
- Preconceptional counselling
- Renal , cardiovascular and retinal assessment
- Target HbA1c <6.1 (NICE guideline 2014)
> 10% : Avoid pregnancy
- Stop ACE inhibitor, ARB or statins
- Self monitoring of blood glucose

28. Diabetic retinopathy – Management in
pregnancy
Preconceptional
• Ideally PDR should be diagnosed & treated before
conception
During pregnancy
– Minimal retinopathy at conception - Fundus every trimester
– Moderate background retinopathy - each visit (4-6 weekly)
– Proliferative DR - laser photocoagulation
– Development of high risk - laser photocoagulation
characteristics
(Br J Ophthalmol 1997;81:249-251)

29. Diabetic nephropathy
• Mild to moderate renal dysfunction
(S.creatinine <1.4mg/dL and cr clearence >90ml/min),
– pregnancy perse does not worsen the long term
outcome.
• Pregnancy accelerates the renal function deterioration
in women with moderate to severe renal dysfunction at
beginning of pregnancy
(Clin of North Am 2007)

30. Medical nutrition therapy
• Primary therapy for 30–90% of women diagnosed
with GDM
• Total calorie intake
BMI <25 kg/m2 3000 cal/day
BMI 25- 30 2500 cal/day
BMI > 30 1250 cal/day

31. • Requirement : < 45% CHO, 30% protein , 25%
fat
• 3 major , 3 minor meals at equal interval
• Diet rich in fiber
• Close observation on weight gain

32. Exercise
• 30 minutes of moderate-intensity aerobic
exercise at least 5 days a week or a minimum
of 150 minutes per week
(ACOG 2018)

33. Indicators for starting insulin
Maternal
• If MNT fails to
achieve glycemic
goals within 2
weeks
Fetal
• Fetal abdominal
circumference at 29-33
wks >75 percentile
(Buchanan et al .Diabeti Care1994;17:275)

34. Types of insulin
TYPE ONSET PEAK DURATION
ULTRA-SHORT ACTING
Lispro, Aspart, Glulisine
0-15min 30-90min 4-5hrs
SHORT-ACTING
REGULAR
30-45min 2-4hrs 6-8hrs
INTERMEDIATE ACTING
NPH
Lente
(semilente+ultralente)
1-2hrs
1-2.5hrs
4-10hrs
6-12hrs
18-24hr
20-24hr
LONG-ACTING Ultra-lente
Glargine
4- 8hrs
1hr
8-12hrs
none
36hrs
24hrs

35. • If insulin is used throughout the day in women
in whom fasting and postprandial
hyperglycemia are present after most meals, a
typical starting total dosage is 0.7–1.0 units/kg
daily. ( ACOG practice bulletein 2018)

36. Insulin therapy
• Calculate total dose
– ( 2/3- intermediate acting (isophane) + 1/3 short
acting insulin
– 2/3 of the dose in morning and 1/3 in evening
– Morning-2/3 isophane+ 1/3 short acting
– Evening -1/2 isophane+1/2 short acting

37. Insulin therapy- facts
Morning dose
Abdomen
(15-30min)
Lunch & dinner
Arm
(30-45min)
Bedtime dose
Thigh
(45-60min)
Maximum
absorptio
n
Slow
absorption
, longer
effect

38. OBSTETRICAL
MANAGEMENT

39. Management
• GDM on diet
– Wait for spontaneous onset of labour
– Timing of delivery not be before 39 weeks of
gestation, unless otherwise indicated ( ACOG practice
bulletein , 2018)
• On insulin
– Followed with antepartum fetal surveillance as
pregestational DM
– Elective induction 38-39 wks

40. Antepartum Fetal Surveillance
1) DFMC daily All patients
2) NST twice weekly controlled IDDM- start
at 32 -34 wks
Start at 28-32 weeks if IUGR, PIH,
Nephropathy,
insulin req >100U/day,
prev still
birth
3)
Biophysical
profile
weekly
4) Doppler in early detection of

41. Timing of delivery
• Plan for induction at 39 week- If well controlled
• If EFW >4.5kg- elective LSCS
(ACOG practice bulletein2018 )
• ELECTIVE LSCS
– Plan early morning
– NPO
– Morning dose withheld
– GIK regime to be started
– Precaution : Adequate incision , use of forceps to deliver high
floating head, check for extension of incision

42. Post-partum management
• Insulin requirement decreases rapidly (first 24-72 hrs)
Vaginal delivery
• GDM
– on diet - no monitoring required
– on insulin - fasting & PP values before discharge
• Pregestational DM
– Starting regular diet
– One half of the pre-pregnancy dose ( PPD1)
ACOG 2005
– 1/2-1/3 of pre-delivery dose ( if pre pregnancy not known)

43. Post-partum management
After cesarean delivery
• Blood sugar monitoring 4-6 hrly
• Regular insulin - if blood sugar >140 -150
mg/dl first 24-48 hrs
• Insulin requirement decreases in lactating
women

44. Post partum glucose testing
• 6-12 weeks postpartum
• 75g glucose testing
Diabetes
mellitus
Impaired
Glucose
tolerance
FBG
(<110mg/dl)
≥7.0 mmol/L
(126 mg/dl)
6.1 - 7.0 mmol/L
(110 -125mg/dl)
2 hr
(<140mg/dl)
≥11.1 mmol/L
(200 mg/dl)
≥7.8 mmol/L≤11.1 mmol/L
(140- 199 mg/dl)

45. Oral Hypoglycemic Agents
in Pregnancy

46. Metformin
• Gilbert et al. systemic review and meta analysis
– Treatment with metfromin in first trimester was associated
with 57% protection effect with an anomaly rate of 1.7% in
metformin group and 7.2% in control group.
Metformin use not associated with major malformations
(Can J Pharmacol 2005;12(1):125)
• In women who decline insulin therapy or who the obstetricians
or other obstetric care providers believe will be unable to safely
administer insulin, or for women who cannot afford insulin,
metformin is a reasonable alternative choice( Level B)
( ACOG practice bulletein , 2018)

47. Glyburide
• Second generation sulphonylurea
• Does not cross placenta (fetal levels <1% of maternal levels)
• Glyburide treatment should not be recommended as a first-
choice pharmacologic treatment because, in most studies, it does
not yield equivalent outcomes to insulin.(Level B)
( ACOG practice bulletein , 2018)

48. Contraception
• Barrier methods - high failure rates
• Intrauterine devices - no increased risk of PID in all diabetics.
Can be used safely
(Kjos et al.Obstet Gynecol Clin North Am 1996;23:243-58)
• Combined OCP’s –
– Use lowest dose COC
– Avoid if hypertension and other cardiovascular risk factors
present
• Minipill – impaired glycemic control
( progesterone induced hyperglycemia)
• Injectables – avoided as they cause altered lipid profile, Glucose
intolerance
Indication - estrogen contraindicated
- non compliance ( WHO 1999)

49. Summary
• Maternal and Fetal outcome
• Screening test and Diagnosis
• Management

50. References
• Aria’s Practical guide to high risk pregancy , 4th
edition
• ADA Standards of care, 2018
• ACOG Practice bulletein ,2018
• Essentials of Obstetrics, First edition

51. THANK YOU