Lecture for incoming first year residents of the Department of Medicine, Philippine General Hospital

1. DIABETES IN
PREGNANCY
Iris Thiele Isip Tan MD, FPCP, FPSEM
Clinical Associate Professor
UP College of Medicine
Section of Endocrinology, Diabetes & Metabolism
Department of Medicine, Philippine General Hospital

2. Definitions
Gestational Pre-gestational
diabetes diabetes

3. Gestational Diabetes
Definitions
Any degree of glucose
intolerance with onset or first
recognition during pregnancy
Metzger BE, Coustan DR (Eds.): Proceedings of the Fourth International Workshop-
Conference on Gestational Diabetes Mellitus. Diabetes Care 21 (Suppl. 2):B1– B167, 1998

4. Pre-gestational Diabetes
Definitions
Diabetes diagnosed before
pregnancy

5. Gestational Diabetes
Screening and diagnosis
Rationale for treatment
Monitoring of blood glucose
Diet and exercise
Insulin initiation and follow-up
Maternal and fetal surveillance
Labor and delivery
Postpartum follow-up

6. Screening
Risk factors for GDM
Increasing maternal age and weight
Previous GDM
Previous macrosomic infant
Family history of diabetes among
first-degree relatives
Gestational
diabetes Ethnic background with a high
prevalence of diabetes
International Diabetes Federation (2009)
Global Guideline on Pregnancy and Diabetes

7. Screening
Screen all pregnant women
“... women with GDM without
risk factors appear to be no
different from women with GDM
Gestational and risk factors.”
diabetes
International Diabetes Federation (2009)
Global Guideline on Pregnancy and Diabetes

8. Screening
All women should undergo
screening at first prenatal visit and
after 26th week AOG if negative
on previous testing
Gestational
diabetes
AFES Study Group on Diabetes in Pregnancy (ASGODIP), 1996

9. Screening
50-g glucose Oral glucose
challenge test tolerance test (OGTT)
(GCT) 75-g or 100 g?
Gestational “A one-stage definitive
diabetes procedure is preferred.”
International Diabetes Federation (2009)
Global Guideline on Pregnancy and Diabetes

10. 75-g OGTT
CHO intake of at least 150 g/day 3 days prior
Fast for 10 to 16 hours
75 grams of anhydrous dextrose powder as chilled 25%
solution (400 cc) flavored with calamansi
Drink within 5 minutes (first swallow is time zero)
Terminate test should nausea and vomiting occur
Collect samples at 0, 1 and 2 hours

11. 75-g OGTT
Abstain from tobacco, coffee, tea, food and
alcohol during test
Sit upright and quietly during the test
Slow walking is permitted but avoid vigorous
exercise

12. Diagnosis
>130 mg/dL
50-g glucose Oral glucose
challenge test tolerance test (OGTT)
(GCT) 75-g or 100 g?
Thresholds ADA
ASGODIP
for
diagnosis 100-g 75-g 75-g
Gestational FBS 95 95 -
diabetes
1h 180 180 -
2h 155 155 140
3h 140 - -

13. Rationale for treatment
Increased risk for
macrosomic or LGA infants
GDM Normal
100
75
Gestational
50
%
diabetes
25
0
MMC VMMC PoGH CSMC PGH
AFES Study Group on Diabetes in Pregnancy (ASGODIP), 1996
Isip-Tan unpublished data

14. Rationale for treatment
Increased risk for
Cesarean sections
GDM Normal
100
80
Gestational
diabetes 60
%
40
20
MMC VMMC PoGH PGH
AFES Study Group on Diabetes in Pregnancy (ASGODIP), 1996
Isip-Tan unpublished data

15. Monitoring blood glucose
Self-monitor blood glucose levels
both fasting and postprandial,
preferably 1 h after a meal.
Gestational
diabetes
International Diabetes Federation (2009)
Global Guideline on Pregnancy and Diabetes

16. Monitoring blood glucose
5th Int’l Workshop NICE CDA
90-99 mg/dL 63-106 mg/dL 68-94 mg/dL
Fasting
(5.0-5.5 mmol/L) (3.5-5.9 mmol/L) (3.8-5.2 mmol/L)
1 h after <140 mg/dL <140 mg/dL 99-139 mg/dL
meal (<7.8 mmol/L) (<7.8 mmol/L) (5.5-7.7 mmol/L)
2 h after <120-127 mg/dL 90-119 mg/dL
meal (<6.7-7.1 mmol/L) (5.0-6.6 mmol/L)
Fifth International Workshop-Conference on Gestational Diabetes Mellitus (2007)
National Institute for Health & Clinical Excellence (2008)
Canadian Diabetes Association (2008)

17. Monitoring blood glucose
Measure HbA1c in women with
gestational diabetes who may
have developed type 2 diabetes
while pregnant
Gestational
diabetes
International Diabetes Federation (2009)
Global Guideline on Pregnancy and Diabetes

18. Dietary Management
Determine if patient is overweight
Expected pregnant weight =
ideal body weight (for height) +
expected weight gain/trimester

19. IOM recommendations for weight
gain by pre-pregnancy BMI
2009
Rates of weight gain*
Total weight
Prepregnancy BMI 2nd and 3rd trimester
gain (lbs)
(lbs/week)
Underweight 1
<28-40
BMI <18.5 (1-1.3)
Normal weight 1
25-35
BMI 18.5-24.9 (0.8-1)
Overweight 0.6
15-25
BMI 25.0-29.9 (0.5-0.7)
Obese 0.5
11-20
BMI >30.0 (0.4-0.6)
* Assume a 0.5-2.0 kg (1.1-4.4 lbs) weight gain in the first trimester

20. Dietary Management
Recommended Daily Caloric Intake
Pregravid BMI Category kcal/kg/day
Low (BMI <18.5 kg/m2) 36-40
Normal (BMI 18.5-24.9 kg/m2) 30
High (BMI 25-29.9 kg/m2) 24
Obese (BMI >29.9 kg/m2) 12
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

21. Dietary Management
For considerably overweight
women with GDM, reduce energy
intake by no more than 30% of
habitual intake
Total cal/day = 1,800-2,000
Not less than 2,000 cal/day if multiple pregnancy
International Diabetes Federation (2009)
Global Guideline on Pregnancy and Diabetes

22. Dietary Management
3 meals and 3 snacks
50-60% complex high fiber CHO
18-20% CHON or at least 75 g
<30% fats

23. Dietary Management
Avoid concentrated sweets
No cookies, cakes, pies, soft
drinks, chocolate, table sugar,
fruit juice, juice drinks, Kool-Aid,
Hi-C, nectars, jams or jellies
Avoid convenience foods
No instant noodles, canned
soups, instant potatoes, frozen
meals or packaged stuffing
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

24. Dietary Management
Eat small frequent meals
Eat about every 3 hours
Include a good source of protein
at every meal and snack (i.e. low-
fat meat, chicken, fish, low-fat
cheese, nuts, peanut butter,
cottage cheese, eggs and turkey)
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

25. Dietary Management
Eat a very small breakfast
No more than 1 starch exchange
(<15 g CHO so limit cereal,
bread, pancakes, toast, bagels,
muffins and Danishes and no
fruit or juice
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

26. Dietary Management
Choose high-fiber foods
Fresh and frozen vegetables
Beans and legumes
Fresh fruits (except at breakfast)
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

27. Dietary Management
Free foods - eat as desired
cabbage mushrooms celery
radish cucumber zucchini
lettuce green beans spinach
onion green onion garlic
broccoli asparagus nopales
spinach lemon/lime butter
olives sour cream avocado
olive oil
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

28. Dietary Management
Monitor urine ketones before
breakfast to detect starvation
ketonuria
Individualize!
Monitor blood glucose levels, urine
ketones, appetite and weight gain

29. Exercise
ACOG (expert opinion)
minimum of 30 minutes exercise
on most days of the week for a
normal pregnancy
Exercise is a useful adjunct to treatment
Avoid excessive abdominal muscle contraction
International Diabetes Federation (2009)
Global Guideline on Pregnancy and Diabetes

30. Insulin Initiation
ADA Protocol
Fasting whole BG >95 mg/dL
1-h postprandial whole BG >140 mg/dL
2-h postprandial whole BG >120 mg/dL
Dr. Jovanovic
Fasting plasma glucose >90 mg/dL (5 mmol/L)
1-h postprandial whole BG >120 mg/dL (6.7 mmol/L)
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

31. Insulin Initiation
Diet therapy alone for at least
2 weeks before starting insulin
If fasting glucose (on OGTT) >95 mg/dL,
start insulin after 1 week of dietary
therapy or at diagnosis

32. Insulin Regimens
Human insulin
Insulin analogues
Insulin lispro and aspart safe and effective
Limited experience with insulin glargine and detemir

33. Insulin Regimens
ASGODIP Protocol
Intermediate-acting insulin 30 min prebreakfast
Intermediate-acting insulin 30 min presupper + rapid-
acting insulin
Three injections of rapid-acting insulin given 30 minutes
before each meal + intermediate-acting OR long-acting
insulin at bedtime
Initiating dose depending or start on a daily dose of 0.1 to
0.3 u/kg BW.

34. Subsequent visits
Date
ASGODIP Protocol
time CBG Comments
11/20
Every 2 weeks to check
glycemic control
after 160 pancakes
breakfast WOF obstetric complications
after 148 spaghetti (i.e. macrosomia, IUGR,
lunch preeclampsia and hydramnios)
after 118
dinner

35. Maternal
surveillance
Increased frequency of preterm
birth in untreated GDM
Use of corticosteroids not
contraindicated but intensify glucose
monitoring and adjust insulin
Risk of hypertensive disorders
increased
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

36. Fetal surveillance
ASGODIP Protocol
Ultrasound at first visit to
determine age of pregnancy
At 20-22 weeks to detect
malformations
At 32-34 weeks to monitor growth
HbA1c values >7.0% or fasting plasma
glucose >120 mg/dL (6.7 mmol/L)
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

37. Glycemic control during
labor and delivery
ASGODIP Protocol
Infusion of 500 ml 5% dextrose/saline x 4 h
CBG q 4 h
Short-acting insulin for CBG > 140 mg%
Dose equal to mmol of CBG i.e. 12 u for 12 mmol/L
Dose equal to 1/20th of mg/dL CBG i.e. 12 u for 240 mg/dL
Omit insulin for CBG < 140 mg/dL

38. Glycemic control during
labor and delivery
ASGODIP Protocol
After delivery, resume diet
Generally do not require insulin
GDM with high insulin requirements during pregnancy
should have CBG monitoring
Give insulin only if CBGs persistently high (>200 mg/dL)

39. Postpartum
follow-up
Schedule 75-g OGTT after 6 weeks
60-70% chance of developing GDM in
subsequent pregnancies
40-60% chance of developing type 2
diabetes in the future
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

40. Postpartum
follow-up
Annual follow-up
Measure FBS
Assess weight reduction
Review pregnancy plans
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

41. Pre-gestational diabetes
Preconception care
Monitoring of blood glucose
Hypoglycemia
Special considerations

42. Preconception Care
Contraceptive advice
Risks of pregnancy (maternal and
fetal/neonatal)
Importance of maintaining blood
glucose levels
Genetic counseling
Personal commitment by women
and her family
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

43. Preconception Care
Prepregnancy Assessment
History and PE
Gynecologic evaluation
Lab evaluation
HbA1c, urinalysis and culture, 24-h
urine for Crea Cl and CHON
Thyroid panel: FT4 1.0-1.6 and TSH
<2.5 uU/L
ECG or treadmill
Neuropathy testing if indicated
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

44. Preconception Care
Potential Contraindications to Pregnancy
Ischemic heart diease
Active proliferative retinopathy, untreated
Renal insufficiency
Crea Cl <50 ml/min or serum crea >2 mg/dL or
heavy proteinuria (>2 g/24 h) or hypertension (BP
>130/80 mm Hg despite treatment)
Severe gastroenteropathy
Nausea/vomiting, diarrhea
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

45. Preconception Care
Shift Type 2 diabetics on OHA to insulin
Maternal HbA1c to assess risk of malformations
Goal <1% above normal range, lower if possible
Monitor every 1 to 2 months
Discontinue contraception
Stable glycemic control
Maternal diabetic complications and coexisting medical
problems acceptable
Diabetes Care 26:S91-93, 2003

46. Monitoring blood glucose
No data to suggest that
postprandial monitoring has a
specific role beyond what is
needed to achieve HbA1c
Pre-gestational
diabetes
Diabetes Care 26:S91-93, 2003

47. Monitoring blood glucose
Self-monitored blood glucose
Fasting/overnight/premeal
plasma glucose 60-99 mg/dL
1-h postmeal 100-129 mg/dL
A1c at initial visit
Monthly until A1c <6.2%
achieved then q2-4 months
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

48. Hypoglycemia
Attempts to achieve normoglycemia in type 1
DM increase risk of hypoglycemia (DCCT)
No evidence that hypoglycemia is an
independent risk to the developing embryo
Clear risk to the mother
Diabetes Care 26:S91-93, 2003

49. Diabetic Retinopathy
May accelerate during pregnancy
Gradual attainment of good metabolic
control before conception
Preconception laser photocoagulation
with standard indications
Baseline dilated comprehensive eye
examination
Follow up eye exam during pregnancy
Diabetes Care 26:S91-93, 2003

50. Diabetic Retinopathy
Risk factors for progression
Duration of diabetes
Retinal status
Elevated HbA1c
Hypertension
Valsalva maneuver (increases risk of retinal
hemorrhage)
Jovanovic L (Ed). Medical Management of Pregnancy Complicated by Diabetes (2009)

51. Hypertension
Type 1 diabetics frequently develop
hypertension in association with
diabetic nephropathy
Type 2 diabetics commonly have
coexisting hypertension
Pregnancy-induced hypertension
proteinuria in excess of 190 mg/day
before conception or in early pregnancy
Diabetes Care 26:S91-93, 2003

52. Hypertension
Aggressive monitoring and control to
reduce risk of worsening
nephropathy, development of
retinopathy or clinical atherosclerosis
SBP <130 mm Hg Avoid ACE-inhibitors, ARBs, beta-
DBP <80 mm Hg blockers and diuretics in women
contemplating pregnancy
Diabetes Care 26:S91-93, 2003

53. Diabetic Nephropathy
Baseline assessment of renal
function before conception and
followed at regular intervals
urine albumin-to-creatinine ratio
24 h albumin excretion
Diabetes Care 26:S91-93, 2003

54. Diabetic Nephropathy
Permanent worsening of renal function
in >40% of women with incipient renal
failure (serum crea > 3 mg/dL or crea
clearance < 50 mL/min)
Permanent worsening of renal function
does not occur more often in women
with less severe nephropathy
Diabetes Care 26:S91-93, 2003

55. Diabetic Nephropathy
Proteinuria >190 mg/24 h before or
during early pregnancy triples risk of
hypertensive disorders in second half of
pregnancy
Risk of IUGR during later pregnancy if
protein excretion > 400 mg/24 h
Discontinue ACE inhibitors in women
attempting pregnancy who have
microalbuminuria
Diabetes Care 26:S91-93, 2003

56. Neuropathy
Autonomic neuropathy may complicate
management
gastroparesis
urinary retention
hypoglycemic unawareness
orthostatic hypotension
Peripheral neuropathy especially compartment
syndromes i.e. carpal tunnel syndrome may be
exacerbated
Diabetes Care 26:S91-93, 2003

57. Cardiovascular disease
Untreated CAD is associated with a
high mortality rate
Successful pregnancies after coronary
revascularization in women with diabetes
Normal exercise tolerance to
maximize probability that patient will
tolerate increased cardiovascular
demands of gestation
Diabetes Care 26:S91-93, 2003

58. Key Points
Screen all pregnant Filipino
women
Be aware of the limitations of
self-monitored blood glucose
Do not wait too long to shift to
insulin if diet therapy fails
Gestational Ensure postpartum OGTT
diabetes

59. Key Points
Counsel diabetic women of
child-bearing potential on
contraception and risks of
unplanned pregnancy with poor
metabolic control
Shift to insulin
Pre-gestational Aim for A1c <1% above normal
diabetes or better

60. Key Points
Advise regarding possible
worsening of diabetic
complications during pregnancy
Discontinue ACE-inhibitors in
albuminuric women attempting
pregnancy
Pre-gestational
diabetes

61. Thank You
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