hyperglycemia during pregnancy

1. HOUY PANHA, MD
Endocrinologist, Diabetologist

2. Outline
1. Introduction
2. Physiopathology
3. Risk factor
4. Screening & Diagnosis
5. T2DM in pregnancy VS GDM
6. The consequent of hyperglycemia
7. Management
8. Take Home Message

3. Objective of Presentation
 Main Objective:
• Screening & Diagnosis of GDM
• Management of GDM
• Obstetrical management in GDM
 Consequent of Hyperglycemia in:
• Fetus
• And mother

4. I. Introduction
GDM is a condition of glucose intolerance which lead to hyperglycemia
that related to pregnancy, onset or recognition during pregnancy.
• It develop in women whose pancreas function is not sufficient to overcome
the glucose regulation change during pregnancy.1
• GDM is different from Pregestational Diabetes that just know during
pregnancy.1
• Hyperglycemia results in both maternal and fetal complications
• Classically, GDM develop after 20 weeks of pregnancy.2

5. Prevalence of GDM in Asia
• Meta-analysis Of Observational
Studies in Epidemiology
• In 8 countries
• Diagnosis criteria: using IADPSG
Cong Luat Nguyen, Ngoc Minh Pham, Colin W. Binns,
Dat Van Duong, and Andy H. Lee. Prevalence of
Gestational Diabetes Mellitus in Eastern and
Southeastern Asia: A Systematic Review and Meta-
Analysis. https://doi.org/10.1155/2018/6536974

7. Glycemic Regulation in Pregnancy
 1er half of pregnancy (Anabolism Phase) => tend to be hypoglycemia almost
at night time and early morning.3
 2nd trimester(20weeks) => tend to be hyperglycemia because of insulin
resistance and increase counter regulatory hormone.3
 Beta-cell function multiplies 2 to 4 time than usual to overcome a good
glycemic regulation.

9. II. Physiopathology
• hLP secret from Placenta4
• Increase progesterone
• In crease counter regulation
hormone
Cortisol
Leptin
GH
• Unsupportable beta-cell function
 Develop to GDM

10. HPL => ⬇ phosphorylation => Alteration of IRS and PI3K => Block GLUT4
from cell membrane=> ⬆ Resistance to Insulin
hPL
LOW GLUCOSE
UPTAKE

11. Pathophysiology of Gestational Diabetes
Mellitus
Gestational
diabetes
mellitus
Insulin resistance
due to placental
secretion of anti-
insulin hormones
Maternal hepatic
glucose production
increases by 15%-
30% to meet fetal
demand late in
pregnancy Pancreatic -cell
dysfunction due to
• Genetics
• Autoimmune disorders
• Chronic insulin
resistance
Inturrisi M, et al. Endocrinol Metab Clin N Am. 2011;40:703-726. Metzger BE, et al. Diabetes Care. 2007;30(2):S251-S260.
11

12. III. Risk factor
☞ Women present at lease one of these criteria are at risk
 History of GDM
 Impaired glucose tolerance
 First degree relative with diabetes
 Excessive weigh gain during 18-24 weeks
 BMI>25kg/m2
 History of Macrosomia
Evidence of insulin resistance
Metabolic abnormalities
Polycystic ovarian syndrome
Age>35 years old
Unexplained miscarriage or
malformation

13. IV. Screening & Diagnosis
• Who should investigate for GDM ?
All pregnant women need to be screened for gestational diabetes.
According to High Prevalence in General Pregnancy Population.
Bad Prognostic in both, fetus and mother if no any Intervention.
• When should investigate ?
Depend on risk factor assessment.6
without Risk: recommend to screen at 24-28 weeks
With Risk: Should screen at the first prenatal visit(<13 weeks) . If negative =>
Repeat at 24-28 weeks.

14. Diagnosis Threshold
Two step approach:
• The first step is a 50g 1H glucose challenge test (GCT).
Screen-positive patients go on to
• the second step, a 100g, 3H oral glucose tolerance test (GTT).
One step approach
• Taking amount of 75g glucose, dosage at OH, 1H and 2H.
☞ One step approach is more simplified and more sensitive for diagnosis
GDM VS Two step approach will miss approximately 25 percent of cases
van Leeuwen M, Louwerse MD, Opmeer BC, Limpens J, Serlie MJ, Reitsma JB, Mol BW. Glucose challenge test for detecting
gestational diabetes mellitus: a systematic review. BJOG. 2012 Mar;119(4):393-401

15. HbA1C & Glycosuria are not
Valuable In Diagnosis of GDM

16. One Step Approach by IADPSG is Preferable
One-step approach test :
☞ At lease one plasma glucose values meet => confirm diagnosis of
GDM
Second VISIT 24-28 weeks
 0H(FPG) >= 92mg/dl
 1H >= 180 mg/dl
 2H >= 153-199mg/dl
FIRST VISIT < 13 weeks
 0H (FPG) >= 92mg/dl
 1H >= 120mg/dl
 2H >`=140mg/dl
van Leeuwen M, Louwerse MD, Opmeer BC, Limpens J, Serlie MJ, Reitsma JB, Mol BW. Glucose challenge test for detecting
gestational diabetes mellitus: a systematic review. BJOG. 2012 Mar;119(4):393-401. Epub 2012 Jan 20.

17. Which One Would You Like ?

18. V. DM in Pregnancy VS GDM
• Pre-gestational diabetes: is defined as Type1 or Type2 DM that
existed before conception.
 Knew and Planning = good
 Diagnosis during pregnancy (Overt DM) = worse
 High risk of of congenital malformations (organogenesis)
 Women are at risk diabetic ketoacidosis
 Aggravated microvascular complication
• GDM : Glucose intolerance during pregnancy only.

19. How To Differentiate these Two ?
Overt DM
 FPG > = 126 mg/dl
 RPG > = 200 mg/dl
 HbA1C > = 6.5%
GDM
 FPG >= 92 - 125
mg/dl
< 13 weeks : OGTT
1H >= 120mg/dl
2H >= 140mg/d
24-28weeks: OGTT
1H >= 180 mg/dl
2H >= 153-199mg/dl
Ian Blumer Eran Hadar David R. Hadden Lois JovanovičJorge H. Mestman M. Hassan Murad Yariv Yogev. Diabetes and
Pregnancy: An Endocrine Society Clinical Practice Guideline. https://doi.org/10.1210/jc.2013-2465

21. Pregestational Diabetes should Be Planed
 Intensive therapy before conception : HbA1c < 6.5% 7
 Complication screening and treatment before conception7
 Contraindication *
• Ischemic heart disease
• Untreated active proliferative retinopathy
• Renal insufficiency
• Severe gastroenteropathy
* Jovanovic L, et al. Mt Sinai J Med. 2009;76:269-280.

22. VI. The Consequent of Hyperglycemia In Fetus
and mother
 HYPERGLYCEMIA gives teratogenic consequent and malformation. 8
 HYPOGLCYEMIA doesn't give teratogenic consequent.
 Complications are strongly interrelated with Glycaemia level in GDM &
HbA1c in Overt DM 8
 Each Complications Risk relate to fetal development phase:8
• 8 weeks organogenesis high risk of teratogen
• > 10 weeks fetal development congenital malformation

24. Insulin Insulin
Glucose, Ketone, Free fatty Acide, Amino Acid *
• Malformation
• Miscarriage
• Macrosomia
• Dystocia
• Hypoxia
• Hyperbilirubinemia
• Pulmonary
Immaturities Hyper-
anabolism
• Hypocalcemia
• Hypoglycemia

25. Pre-gestational DM and fetal Complications
• Abortion 32% if HbA1c > 8% vs 15% in GP 8
• Congenital Malformation 3 time higher than GP
o Cardiac Malformation
o Coarctation of the Aorta
o Ventricalar septal defect
• Neurological malformation
o Spina bifida
o Hydrocephalic
o Anencephalic
• Kidney Malformation
☞ These lead to fetal and new born Death, Malformation in new born, and
Spontaneous abortion

27. Pregnancy Aggravated Complications of DM
mother 9
• Retinopathy
• Nephropathy
• Neuropathy : is not affected by Pregnancy
• Develop to HBP
• Coronary Disease
• Infection
• Autoimmune Thyroid abnormalities

29. Progression
• 41.3% recurrent GDM in second pregnancy
• 20% Impaired glucose tolerance in early postpartum
• 5%-10% of women with GDM develop T2D immediately postpartum*
• 35%-60% chance of T2D over next 10-20 years*
• Infant of GDM are risk
 Obesity in young child
 Type2 diabetes mellitus
 Hypertension in young adult
* ADA. Diabetes Care. 2017;40(suppl 1):S114-S119. Inturrisi M, et al. Endocrinol Metab Clin N Am. 2011;40:703-26. Metzger BE, et al. Diabetes
Care. 2007;30:S251-S60. Committee on Obstetric Practice. ACOG. 2011;504:1-3. CDC. National Diabetes Fact Sheet 2011. CDC.
http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. 2011.

30. VII. Management
 Early Diagnosis
 Early Intervention => Better Outcome
 Intensive Glycemic Control and objective
 Nutrition Therapy
 Exercise
 Pharmacotherapy
 Glycaemia Monitoring and Objective
 Obstetrical Management
 Education

31. Objective Glycemic
Objective by ADA * and ACOG # glucose targets are
• FPG <95 mg/dL (5.3 mmol/L)
• One-hour PPG: <140 mg/dL (7.8 mmol/L)
• Two-hour PPG: <120 mg/dL (6.7 mmol/L)
* American Diabetes Association. 13. Management of Diabetes in Pregnancy: Standards of Medical Care in
Diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S137
# Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus.
Obstet Gynecol. 2018;131(2):e49

33. Monitoring & Follow Up
• Initial of diagnosis, patients asked to measure their own Glycemic 6
times. Before and 2H after each principal meals, at lease 4 times/days
at morning FPG and each post meal. 7
• Base to daily glycaemia profile, we can adjust dose of drug to achieve
Glycemic target.7
• Closely follow up after obtained minimum dose efficacy, because as
pregnancy develop, Insulin requirement also increase.

34.  3 meals time strictly with 2 snacks per day 10
 Total Kcal:
• 30-35 Kcal/kg for women BMI
• 25 Kcal/kg for women overweigh and obesity BMI
 All pregnancy are not recommended to eat less than
1600 kcal/ day
 Avoid high glycemic index foods
Nutrition for GDM
☞ Most women with GDM (70 to 85 percent) can achieve
normoglycemia with nutritional therapy alone.* (ADA)
American Diabetes Association. 13. Management of Diabetes in Pregnancy: Standards of Medical Care in
Diabetes-2018 Diabetes Care. 2018;41(Suppl 1):S137

36. Exercise In Pregnancy
 After Obstetrical Consultation
 Respect Contraindication
 Recommendation by ADA
 Moderate intensity Physical activities for 30mn daily
 Moderate exercise as part of the treatment plan for women GDM and no
medical or obstetrical contraindications.
Colberg SR, Sigal RJ, Fernhall B, Regensteiner JG, Blissmer BJ, Rubin RR, Chasan-Taber L, Albright AL, Braun B, American
College of Sports Medicine, American Diabetes Association. Exercise and type 2 diabetes: the American College of Sports
Medicine and the American Diabetes Association: joint position statement. Diabetes Care. 2010;33(12):e147.

37. Choice of Drugs
• Pharmacotherapy will be placed after Nutrition therapy failed
• Insulin is the drug of choice
• No other Anti-hyperglycemic drug safer than Insulin
• Presentational DM underwent ADO should switch to Insulin
• ADO Metformin and Glyburide are reasonable alternative drugs when
patients refuse insulin.11

39. How to start Insulin ?
• If FPG is high:
o Intermediate-acting insulin(NPH insulin),
o NPH is given before bedtime
o Initial dose of 0.2 unit/kg body weight is utilized
• If PPG are high:
o Rapid-acting insulin such as Actrapid or analogs such as Aspart, Lispro
o Give before meals
o 1 UI to drop 25-50mg/dl glucose based on PPG
o Insulin requirement = (Plasma glycemic – target /25)

40. • If Both FPG&PPG are high:
 Basal bolus should start (50%bsal, 50%bolus)
 Premix 2-3 injection based on Glycemic
 Starting dose is
 0.7 unit/kg < 12w
 0.8 unit/kg for 13-26w
 0.9 unit/kg for 26-36w
 1.0 - 2.0unit/kg for weeks 36 to term
 Insulin Pump is best Adaptation, but High cost and complexity
☞ No one fit all => should be flexible in Real World

42. Insulin injection sites in Pregnancy
NOT Abdominal Region

43. Obstetrical Management
• Regular follow Up
• No any recommendation for Medical Abortion in GDM or DM
pregnancy
• Limit weigh gain
• Delivery plan : Cesarean or Natural labor ?
• Breath feed or formula feed ?
 GDM will stop requiring insulin
 DM Pregnancy still need drugs => can switch to ADO if formula feed
• Insulin and Glycemic during Labor

46. Education
• Explain to patient about complication and risk
• All GDM are Pregnancy with Risk
• Encourage them for strictly control Can Reduce Risk of complication
• Risk of Hypoglycemia
• Recognizing hypo and hyper and Management

49. During Labor
• GDM => Stop Insulin
• Monitor glycemic, objective 100mg/dl.12
• Pregestational DM => +/- Solution D10% and insulin IVSE 12
• Prevention Hypoglycemia and hypocalcemia in new born 12
Post Partum
• screen for DM at 6-12 weeks after delivery (FPG/OGTT)
• Diabetes => Treat
• Prediabetes => intervention (life style + exercise) => recheck every years
• Normal glycemic => recheck every 3 years
GDM, gestational diabetes mellitus.
Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87.
ADA. Diabetes Care. 2017;40(suppl 1):S11-S24.

50.  One step approach OGTT is preferable for Diagnosis
GDM
 All Pregnancy should screen for GDM
 Management of GDM , Objective
 Insulin is Best Choice
 Early management and Intensive glycemic control
provide better Outcome
 Obstetrical follow Up Is important
 Education : Recognize hypoglycemia and
management

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