3. Objectives
• To discuss in brief about Gestational Diabetes
Mellitus with maternal and fetal effect
• To discuss about screening and diagnosis of
Gestational Diabetes Mellitus
• To discuss about treatment of Gestational
Diabetes Mellitus
4. Diabetes mellitus
State of carbohydrate intolerance resulting
from inadequacy of insulin secretion or
ineffectiveness of insulin action.
5. Gestational diabetes
Refers to Carbohydrate intolerance
resulting in hyperglycemia of variable
severity with onset or first recognition
during pregnancy
irrespective of need for insulin and
regardless of whether diabetes persists
after pregnancy.
10. Effects of Insulin
• Nearly all cells (80%) increase glucose uptake
(seconds)
– Active transport
– Primarily affects liver and muscle
– Brain tissue is excepted
• Alters phosphorylation of many key intracellular
metabolic enzymes (minutes)
• Alters protein synthesis and gene transcription
(hours)
11.
12.
13.
14.
15.
16.
17.
18. Insulin and Fat Metabolism
• Liver cells store glycogen only up to 5-6%
– Remaining glucose metabolized to fat
– Triglycerides are synthesized and release into blood
• Adipose cells store fat
– Inhibits breakdown of triglycerides
– Stimulates uptake and use of glucose to form glycerol
– Stimulates fatty acid uptake and conversion to triglycerides
• Lack of insulin
– Free fatty acids build up in blood
– Liver metabolizes to produce phospholipids and cholesterol
– Can lead to excess acetoacetic acid production and buildup of acetone
(acidosis, which can lead to blindness and coma)
19. Insulin and Protein Metabolism
• Promotes
– Transport of amino acids
– Protein synthesis
– Gene transcription
• Inhibits protein degradation
• Prevents glucose synthesis in liver
– Preserves amino acids
• Lack of insulin causes elimination of protein
stores
21. Effects of Glucagon
• Prevents hypoglycemia
– Powerful system to degrade glycogen
– Increases glucose synthesis from amino acids
• Increases with exercise independent of
blood glucose
• Exerts effects through cAMP second
messenger system
22. Insulin Affects Tissues Differently
• Muscle
– Uptake of glucose and immediate use (exercise) or storage as
glycogen (Exercising muscles can take up glucose without insulin)
• Liver
– Uptake of glucose and storage as glycogen
• Inhibits glycogen phosphorylase
• Activates glycogen synthase
• Inhibits glucose synthesis
• Promotes excess glucose conversion to fatty acids
• Adipose Tissue
– Promotes glucose uptake and conversion to glycerol for fat
production
24. Normal pregnancy is characterized by mild fasting
hypoglycemia, postprandial hyperglycemia, and
hyperinsulinemia.
Increased basal level of plasma insulin in normal
pregnancy is associated with several unique
responses to glucose ingestion.
Insulin sensitivity in late normal pregnancy is 45
to 70 percent lower than that of nonpregnant
women (Butte, 2000; Freemark, 2006).
2022/3/18 25
Carbohydrate metabolism
25. • Deterioration of glucose tolerance occurs
normally during pregnancy.
• Significant metabolic changes are necessary to
provide proper energy delivery to the growing
conceptus.
2022/3/18 26
Carbohydrate metabolism
26. • The mechanism(s) responsible for insulin resistance
is not completely understood.
• Progesterone and estrogen may act, directly or
indirectly, to mediate this resistance.
• Rising serum levels of estrogen and progesterone
increase insulin production and secretion while
increasing tissue sensitivity to insulin.
2022/3/18 27
Carbohydrate metabolism
27. • Plasma levels of placental lactogen increase with
gestation, and this protein hormone is characterized
by growth hormone–like action that may result in
increased lipolysis with liberation of free fatty acids
(Freinkel, 1980).
• The increased concentration of circulating free fatty
acids also may aid increased tissue resistance to
insulin (Freemark, 2006).
2022/3/18 28
Carbohydrate metabolism
28. Glucose Metabolism in Pregnancy
• Fetal growth is dependent upon maternal
glucose
• Carbohydrates from maternal diet
• Stored glycogen converted to glucose
• High levels of glucose transported by diffusion
to the fetus
• Fetal production of insulin
29. 1st Trimester
• The overall result is a lowering of the fasting
glucose levels, reaching a nadir by the 12th
week.
• The decrease is on average 15 mg/dL; thus
fasting values of 70-80 mg/dL are normal in a
pregnant woman by the 10th week of
gestation.
2022/3/18 30
30. 2nd Trimester
• In the second trimester, higher fasting and
postprandial glucose levels are seen. This
facilitates the placental transfer of glucose.
• Glucose transfer is via a carrier-mediated
active transport system that becomes
saturated at 250 mg/dL.
2022/3/18 31
31. 2nd Trimester (contd)
• Fetal glucose levels are 80% of maternal values. In
contrast, maternal amino acid levels are lowered
during the second trimester by active placental
transfer to the fetus.
• Fetal levels of amino acids are 2- to 3-fold higher than
maternal levels, but not as high as levels within the
placenta.
• Lipid metabolism in the second trimester shows
continued storage until midgestation; then, as fetal
demands increase, there is enhanced mobilization
(lipolysis).
2022/3/18 32
32. Physiology in Late Pregnancy
Characterized by accelerated growth of the fetus
• A rise in blood levels of several diabetogenic
hormones
• Food ingestion results in higher
and more prolonged plasma glucose concentration
33. Physiology in Late Pregnancy
• Maternal insulin and glucagon do not cross the
placenta
• During late pregnancy a women’s basal insulin
levels are higher than non-gravid levels
• Food ingestion results in a twofold to threefold
increase in insulin secretion
(Franz, M.J., 2001)
34. Physiology of GDM
• Gestational hormones
induce insulin
resistance
• Inadequate insulin
reserve and
hyperglycemia ensues
35. ‘Endocrinology of Pregnancy’
• The placenta produces larger quantities of
more hormones than any other human organ:
– Human placental lactogen
– Estrogen / progesterone
• The majority of its products are released into
the maternal circulation to induce changes on
the fetuses’ behalf.
36. HPL
• HPL is the hormone mainly responsible for insulin
resistance and lipolysis.
• HPL also decreases the hunger sensation and
diverts maternal carbohydrate metabolism to fat
metabolism in the third trimester.
• HPL is a single-chain polypeptide secreted by the
syncytotrophoblast and has a molecular weight of
22,308 and a half-life of 17 minutes.
• HPL levels are elevated during hypoglycaemia to
mobilize free fatty acids for energy for maternal
metabolism.
2022/3/18 37
37. HPL (cont)
• During pregnancy, the levels of HPL rise
steadily during the first and second trimesters
with a plateau in the late third trimester.
• This plateau is the natural result of decreasing
nutrient delivery to the placenta, thus
decreasing hormone production.
2022/3/18 38
38. Cortisol
• Cortisol levels rise during pregnancy and
stimulate endogenous glucose production and
glycogen storage and decrease glucose
utilization.
2022/3/18 39
39. Prolactin
• Prolactin levels are also increased 5- to 10-fold
• may have an impact on carbohydrate
metabolism.
• patients with hyperprolactinemia deserve
early pregnancy glucose screening.
2022/3/18 40
41. Epidemiology
• Abnormal maternal glucose regulation occurs
in 3-10% of pregnancy.
• DOUBLES the risk of serious injury at birth,
TRIPLES the likelihood of caesarean delivery
and QUADRUPLES the incidence of newborn
intensive care unit admission
(eMed.Journal, June 2000 , Vol 3, Number 6)
42. Epidemiology
• The prevalence of GDM in low-risk populations
ranges from 1.4% to 2.8%; in high-risk
populations, prevalence ranges from 3.3% to
6.1%
• Abnormal maternal glucose regulation occurs in
3-10% of pregnancy.
• Prevalence different among different races and
population
43. Approximate Prevalence of Diabetes
in Pregnancy in the United States
GDM=gestational diabetes mellitus
Nondiabetes
92%
More than 200,000 type 2 diabetes mellitus + 135,000 GDM +
6000 type 1 diabetes mellitus = 341,000 pregnancies
complicated by hyperglycemia annually
Diabetes 8%
4.022 Million Births in 2002
50% GDM
Diabetes 8%
2% T1DM
24% Diagnosed
T2DM
44. • GDM represents 90% of all cases of diabetes
mellitus that are diagnosed during pregnancy.
• Compared to European women, prevalence of
gestational diabetes has increased eleven fold in
women from the Indian subcontinent .
• DOUBLES the risk of serious injury at birth,
TRIPLES the likelihood of caesarean delivery and
QUADRUPLES the incidence of newborn intensive
care unit admission
(eMed.Journal, June 2000 , Vol 3, Number 6)
45. Diabetes in Nepal
• Singh and Bhattarai found the rates of DM and IGT
to be 14.6 and 9.1% in urban areas, and 2.5 and
1.3% in rural areas [Diabet. Med. 20 (2003) 170–171]
• Prevalence more in urban population than in the
rural population [Diabet. Med. 20 (2003) 170–171]
• Most of the Nepalese Diabetic patients have poor
KAP scores [Rawal Medical Journal.2008; 33(1):8-11]
• No published studies about prevalence of GDM in
Nepal
46. Importance
Pregnant women with pre-gestational
diabetes are at higher risk for multiple
complications affecting both the mother and
the fetus than those women without diabetes
Obstet Gynecol 2003;101: 380-392.
47. White Classification of Diabetes Mellitus in Pregnancy
GDM:
• Class A1 Gestational diabetes (GDM) not requiring
insulin (or oral agents).
• Class A2 Gestational diabetes requiring insulin (or oral
agents).
Pregestational DM:
• Class B Onset at >20 years of age or duration of <10
years.
• Class C Onset at 10 to 19 years of age or duration of
10 to 19 years, no vascular disease.
48. Cont..
• Class D Onset at <10 years of age or duration of
20 years or more or, any onset/duration but with
background retinopathy or hypertension only.
• Class F Nephropathy (>500 mg proteinuria per
day at <20 weeks of pregnancy).
• Class H Arteriosclerotic heart disease, clinically
evident.
• Class R Proliferative diabetic retinopathy (active)
or vitreous hemorrhage.
• Class T History of renal transplant
49. Causes of GDM
• Inadequate insulin production
• Increased insulin resistance
Or Both!!
• Strong genetic predisposition
• Progressive increased risk until term (but most
clinically significant problems are evident by the early
third trimester)
52. Low-risk status requires no glucose testing, but this category
is limited to those women meeting all of the following
characteristics:
Age <25 years.
Weight normal before pregnancy .
Member of an ethnic group with a low prevalence of
gestational diabetes mellitus .
No known diabetes in first-degree relatives .
No history of abnormal glucose tolerance .
No history of poor obstetric outcome .
Risk assessment
53. Intermediate risk for GDM
• Patients with any one of the following
– Ethnic population except Caucasian, European
– Age > 25
– BMI > 25
• with
– No known diabetes in first degree relative
– No H/O glucose intolerance
– No H/O obstetric complications usually associated with
GDM
5th International Workshop-
Conference on Gestational Diabetes
Mellitus, ADA, ACOG
54. Risk assessment
marked obesity.
personal history of gestational diabetes
mellitus.
Glycosuria.
a strong family history of diabetes .
A high risk of gestational diabetes mellitus:
55. • high risk patients should undergo glucose testing
A fasting plasma glucose level
>125mg/dL or a casual plasma
glucose >200 mg/dL meets the
threshold for the diagnosis of
diabetes
In the absence of this
degree of hyperglycemia,
evaluation for gestational
diabetes mellitus in
women with average or
high-risk characteristics is
by glucose tolerance test .
Risk assessment
56. Screening
• Screening commonly conducted during the
24th to 28th week of gestation
• Using the 140 mg/dl threshold, the GCT is
positive for 14% to 18% of all pregnant
women, including about 80% of women with
GDM
57. Current recommendations for screening
• High risk patients should be screened as early
as possible and repeated at 24-28 weeks if
screening negative
– Strong family history of diabetes
– Prior history of GDM
– Morbid obesity
– Other manifestations of glucose intolerance
5th International Workshop-
Conference on Gestational Diabetes
Mellitus, ADA, ACOG
58. • Patients of intermediate risk should be screened at
24 to 28 weeks
• Recommended screening is 2-step approach, with
50-g 1-hr GCT followed by diagnostic 3-hr 100-g
OGTT
• Glucose challenge test:
– Venous plasma glucose level is measured after 1 hr of 50
gm glucose load without regard to time of day and time of
last meal.
• Threshold value for 1-hr GCT is 130 or 140mg/dl –
either is acceptable
Current recommendations for
screening for GDM
5th International Workshop-
Conference on Gestational Diabetes
Mellitus, ADA, ACOG
59. 50-g oral glucose challenge
The screening test for GDM, a 50-g oral glucose
challenge, may be performed in the fasting or fed
state. Sensitivity is improved if the test is performed
in the fasting state .
A plasma value above 130-140 mg one hour after is
commonly used as a threshold for performing a 3-
hour OGTT.
If initial screening is negative, repeat testing is
performed at 24 to 28 weeks.
62. 3 hour Oral glucose tolerance test
Prerequisites:
- Normal diet for 3 days before the test.
- No diuretics 10 days before.
- At least 10 hours fast.
- Test is done in the morning at rest.
Giving 75 gm (100 gm by other authors) glucose in 250 ml water orally
Criteria for glucose tolerance test:
The maximum blood glucose values during pregnancy:
- fasting 90 mg/ dl,
- one hour 165 mg/dl,
- 2 hours 145 mg/dl,
- 3 hours 125 mg/dl.
If any 2 or more of these values are elevated, the patient is considered to have
an impaired glucose tolerance test.
63. Diagnosis of GDM with a 100-g or 75-g glucose load
100 gm Glucose load mg/dl mmol/L
Fasting 95 5.3
1 hr 180 10.0
2 hr 155 8.6
3 hr 140 7.8
75 gm glucose load
Fasting 95 5.3
1 hr 180 10.0
2 hr 155 8.6
Two or more of the venous plasma concentrations must be met or exceeded for
a positive diagnosis. The test should be done in the morning after an overnight
fast of between 8 and 14 h and after at least 3 days of unrestricted diet
(≥150 g carbohydrate per day) and unlimited physical activity.
The subject should remain seated and should not smoke throughout the test.
Diabetic care
64. GDM Criteria
National
Diabetes Data
Group*
American
Diabetes
Association*
World health
Organization †
Carpenter and
Coustan*
Fasting 105 95 ≥ 126 95
1 hour 190 180 - 180
2 hours 165 155 ≥ 140 155
3 hours 145 - 140
*2 or more criteria met = positive diagnosis (cutoff points in mg/dl)
† 1 or more criteria met = positive diagnosis
65. A POSITIVE SCREEN DOES NOT
ESTABLISH THE DIAGNOSIS OF
GESTATIONAL DIABETES!!!
66. Adverse Pregnancy Outcomes
• Maternal risks:
– Pre-eclampsia: affects 10-25% of diabetic pregnancies.
– Increased operative vaginal deliveries and consequent
trauma
– polyhydramnios
– Increased C-section
– PPH: due to overdistension of uterus
– Infection: due to chorioamnionitis and post partum
endometritis
– >50% of women with gestational diabetesn will develop
overt DM in ensuing 20 yrs
– Recurrence rate: 35-50%
67. Potential Complications in
Infants of Mothers With Diabetes
• Intrauterine demise
– Spontaneous abortion
– Stillbirth
• Macrosomia
• Visceromegaly
– Cardiomegaly
– Hepatic enlargement
• Birth injury
– Shoulder dystocia
– Erb’s palsy
– Diaphragmatic paralysis
– Facial paralysis
– Cerebral ischemia
– Hemorrhage in brain, eyes,
liver, genitalia
Jovanovic L, ed in chief. Medical Management of Pregnancy Complicated by Diabetes.
3rd ed. Alexandria, Va: American Diabetes Association; 2000:133-149
68. – Macrosomia:
• Birth weight >4500gm (ACOG)
• Occurs in 17-29% of gestational diabetes(ACOG: 12%)
• Patho physiology:
maternal hyperglycemia
Fetal hyperglycemia
Fetal hyperinsulinemia
Excess somatic growth
• Consequent complications:
– Shoulder dystocia. Brachial plexus injury, clavicular fracture
– Risk of fetal anomalies and fetal death more in overt
diabetes
69. • Cardiac( including great vessel anomalies) : most
common
• Central nervous system: 7.2%
• Skeletal: cleft lip/palate, caudal regression
syndrome
• Genitourinary tract: ureteric duplication
• Gastrointestinal : anorectal atresia
Fetal congenital anomalies
73. Fetal
hyperinsulinemia
The Impact of Maternal Hyperglycemia
During Pregnancy
Modified Pedersen Hypothesis
Fetus
Fetal pancreas stimulated
IgG=immunoglobulin G Mother
Placenta
IgG-antibody-bound insulin
Insulin
Maternal hyperglycemia
Insulin resistance syndrome
74.
75. Monitoring
Urine glucose monitoring is not useful in
gestational diabetes mellitus. Urine ketone
monitoring may be useful in detecting
insufficient caloric or carbohydrate intake in
women treated with calorie restriction.
76. Daily self-monitoring of blood glucose
(SMBG) appears to be superior to
intermittent office monitoring of
plasma glucose.
Monitoring
77. For women treated with insulin, preprandial
monitoring is superior to postprandial
monitoring. However, the success of either
approach depends on the glycemic targets
that are set and achieved.
Monitoring
78. Glycosylated haemoglobin (Hb A1(
It is normally accounts for 5-6% of the total haemoglobin
mass. A value over 10% indicates poor diabetes control in
the previous 4-8 weeks.
If this is detected early in pregnancy, there is a high risk of
congenital anomalies .
If this is detected in late pregnancy it indicates increased
incidence of macrosomia and neonatal morbidity and
mortality.
Monitoring
79. The mean glucose represented by the hemoglobin A1c
level can be calculated using the "rule of 8's." A value
of 8 percent equals 180 mg/dl, and each 1 percent
increase or decrease represents ± 30 mg/dl.
Glycosylated haemoglobin (Hb A1(
Monitoring
80. Assessment for asymmetric fetal growth by
ultrasonography, particularly in early
third trimester, may aid in identifying
fetuses that can benefit from maternal
insulin therapy
Monitoring
81. Maternal surveillance should include
blood pressure and urine protein
monitoring to detect hypertensive
disorders.
Monitoring
82.
83. Goals of management
• Achieving glycemic targets
• Nutritional counseling from an Registered
Dietitian
• Encouraging physical activity
• Avoiding ketosis
• Initiating and maintaining insulin therapy
• Arrangement and planning of delivery
• Post partum follow-up and management
84. 2 groups of patients
• Pregnant ladies with established diabetes
(type I or type II)
• Pregnant ladies with new onset diabetes
(GDM)
85. • SMBG (self-monitoring of blood glucose)
– Fasting/premeal: 80 to110 mg/dL
– 1 hour postmeal: <155 mg/dL
• HbA1C
– In normal range (<6%, but ideally <5%)
– Target value of HbA1C is stable at <7
Preconception Care of Established Diabetes
Joslin Diabetes Center and Joslin Clinic; Guideline for Detection
and Management of Diabetes in Pregnancy 9/14/2005
86. Medical Goals
• Switch from oral agent therapy to physiologic basal-bolus insulin
replacement (type 2 diabetes)
• Prevent hypoglycemia and ketoacidosis
• Blood pressure <130/80 mm Hg
• Protein excretion levels <150 mg/24 hours
• Free T4 >1.0 but <1.6 ng/dL
TSH <2.5 IU/mL
• Establish medical team for ongoing management
Preconception Care of Established Diabetes
American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S76-S78
87. Exception to discontinuing oral anti-diabetic
medication during pregnancy
Metformin may be continued during first
trimester on patients with PCOS or type 2 DM
with anovulatory infertility
At first visit should begin increasing insulin to
control blood sugar and taper off metformin
88. What about other medications!!!
• Gliburide
• Other OHA’s
• ACE inhibitors
• ARBs
• All cholesterol lowering agents.
89. Booking Antenatal visit for existing Diabetic Patients
• HbA1C
• 24 hr urine (protein, creatinine clearance, creatinine)
• EKG
• Eye examination
• Renal function tests (Class D-T)
• Dating scan at 10 – 12 weeks
90. GDM Screening and Diagnosis
Universal Screening Guidelines
Average and high risk: Screen at intake
Low risk: Screen at 24 to 28 weeks’ gestation
Screen with
1-h 50-g GCT
180 mg/dL
STOP
Check Fasting BS
>95 Diabetic
Refer to HEd, A1C
140–180 mg/dL
Administer FPG and
3-h 100-g OGTT
on separate day
130 mg/dL
STOP
Patient does not
have GDM
If FPG 95 mg/dL
STOP
Patient has GDM
Refer to Health Ed
Otherwise, administer
3-h 100-g OGTT
(2 or more abnormal
values,
patient has GDM)
1 h 180 mg/dL
2 h 155 mg/dL
3 h 140 mg/dL
If patient has GDM
risk factors, rescreen
at 24–28 weeks’
gestation
Rescreen later in
gestation
FPG=fasting plasma glucose
Jovanovic-Peterson L et al. Am J Perinatol. 1997;14:221-228 /ADA 2006 Diabetes Care
91. SMBG –Pregnancy Complicated by Diabetes
Blood Glucose Goals and Testing Frequency
Goal Timing
Fasting 60–90 mg/dL Test on waking from bed
Pre-meal 60–90 mg/dL Test before each meal
1-hour postprandial
2-hour postprandial
100–130 mg/dL
100-120 mg/dl
Test 1 hour after each meal
screens for highest sugar
exposure to fetus.
Some Perinatologist prefer 2 hour
Postprandial check
11:00 PM–4:00 AM 60–100 mg/dL Test at bedtime or in middle of the
night*
*2:00–4:00 AM if nocturnal hypoglycemia is suspected
92. • 3 daily meals; snack as needed
• Small breakfast
• Control of carbohydrate intake;
– low glycemic foods. Minimal 130 grams of CHO.
• High fiber diet
• Foods with low saturated fat
• Avoiding concentrated sweets
• multivitamin with iron, folic acid, and calcium
Nutrition Therapy
General Dietary Guidelines
93. Physical Activity in GDM
• Improves peripheral insulin resistance and glucose levels
• Obviate need for insulin
• Encouraged for women with no obstetric contraindications
Jovanovic-Peterson L et al. Am J Obstet Gynecol. 1989;161:415-419
94. Energy requirement
25 years female IBW 60 kg
Carbohydrate (65%) 450
Protein (10%) 70
Fat (25%) 180
Carbohydrate 100 gm
Protein (10%) 15 gm
Fat (25%) 17 gm
Diet Carbohy. Protein Fat _
Arabian bread 30 gm --- ---
Cheese 5 gm 10 gm 10 gm
Honey 50 gm 2 gm 3 gm
Glass of milk 10 gm 5 gm 5 gm_
Total 95 gm 17 gm 18 gm
Carbohydrate (65%) 590
Protein (10%) 90
Fat (25%) 220
Carbohydrate 130 gm
Protein (10%) 20 gm
Fat (25%) 22 gm
Diet Carbohy. Protein Fat _
Rice 80 gm --- 6 gm
chicken 5 gm 15 gm 12 gm
Salad 30 gm 4 gm 4 gm
Orange 10 gm --- ---___
Total 125 gm 19 gm 22 gm
Carbohydrate (65%) 330
Protein (10%) 50
Fat (25%) 120
Carbohydrate 65 gm
Protein (10%) 10 gm
Fat (25%) 11 gm
Diet Carbohy. Protein Fat _
Tuna sandwich 45 gm 12 gm 10 gm
Apple 15 gm --- ---
Tea --- --- --- _
Total 95 gm 17 gm 18 gm
60 Kg X 30 kcal = 1800 kcal
with 30% extra= 2100 Kcal
Breakfast 700 kcal Lunch 900 kcal Dinner 500 kcal
100. Can OHA be used to treat GDM?
• Glyburide
– Does not cross the placenta
– Controlled BG in 80% of women
– Women with high FBG less likely to respond to Glyburide
– More adverse perinatal outcomes compared to insulin
– use is considered off-label and requires appropriate
discussions of risks with patient
101. Metformin
– alone or with insulin was not associated with increased
peri-natal complications compared with insulin
– Less severe hypoglycemia in neonates
– Does cross the placenta – long term study MiG TOFU ongoing
– use is considered off-label and requires appropriate discussions
of risks with patient (NEJM, 2008)
Contd…
102. Metformin in GDM
• Metformin versus Insulin for the Treatment of
Gestational Diabetes751 women with GDM randomly
assigned to metformin (with supplemental insulin if
needed) or insulin
– Metformin group: 92.6% continued until delivery, 46.3%
received supplemental insulin
– Primary and secondary outcomes were statistically similar
– Women preferred metformin to insulin
• No studies to compare metformin and glyburide
Rowan J. MiG Trial, NEJM, May 2008
103. Insulin
• Polypeptide hormone
• Secreted by β cells of pancreas
• Discovered by
Frederick Banting and Charles Best (1921)
• Leonard Thompson (age 14, 65lbs) first
patient successfully treated.
104. Insulin Preparation
Action Name Onset Duration
Very rapid Lispro / Novo rapid 10-15 min 2-3 hrs
Rapid Crystalline zinc (CZI) 30-45 min 4-6 hrs
Intermediate Neutral Protamine
Hagedorn (NPH) 1-2 hrs 6-12 hrs
Lente zinc
Long acting Ultralente zinc 6-8 hrs 18 hrs
Lantus (glargine) 4-8 hrs 24 hrs
Premixed 80% NPH+20%CZI 30-45 min 6-12 hrs
70% NPH+30%CZI 30-45 min 6-12 hrs
50% NPH+50%CZI 30-45 min 6-12 hrs
105. • Fast acting: Humalog , NovoRapid
• Short acting: Regular/R
• Intermediate acting: NPH/N
– Detemir can be used if woman unable to tolerate NPH (
Ongoing study to evaluate use in pregnancy)
– Glargine – avoid use
• Human Insulins-Least Immunogenic
Breastfeeding mother- All types insulin considered safe
Insulin Safety in Pregnancy
108. Insulin Delivery Throughout Pregnancy
Daily Insulin Dose for Pregnancy with Preexisting Diabetes
Gestational
week
4–12
12–24
24–38
38–42
0.7 U
0.8 U
0.9 U
1.0 U
Insulin dose
Multiplied by
current
pregnant
weight in kg
Jovanovic L. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY:
Marcel Dekker Inc; 2002:139-151
109. Principles for Insulin
• Calculation of total dose required
• Divided into 2 doses
• 2/3 in morning
• 1/3 in evening
• NPH + Regular or rapid acting in AM, regular or
rapid acting at supper, NPH at bedtime
• Regular or rapid acting (lispro or aspart) with
meals, NPH at bedtime
110. Alternate Insulin Dosing in GDM
• For tight control “SPLIT REGIMEN”
• ½ dose divided into 3 parts
• ½ dose at night
111. Insulin: when to initiate?
Blood glucose ADA ACOG
Fasting ≤105 mg/dL >95 mg/dL
1hr pp ≤155 mg/dL
2hr pp ≤130 mg/dL >120 mg/dL
112. The total dose of required for a pregnant lady is
calculated according to the patient’s weight as follows:
Insulin therapy …..cont.
In the first trimester .......... weight x 0.7
In the second trimester........ weight x 0.8
In the third trimester........... weight x 0.9
113. Blood sugar moderately elevated
– Mixed insulin started
– 50:50 or 30:70
Blood sugar highly elevated
– Continuous insulin infusion
– Total 24 hour dose identification
– After identifying mixed insulin
DKA
– Continuous insulin infusion
114. Insulin Dose adjustment
• 4 parameters measured
– Fasting blood sugar
– Post-lunch or PP
– Pre-dinner
– Post dinner
• Measurement should be done atleast 48 hours of
insulin dose adjustment
NEXT
115. • Very high parameter
–supplemental regular insulin
• Insulin dose readjustment
–Depending upon the derangement
NEXT
Insulin Dose adjustment
116. • High morning levels, but controlled evening levels
• Controlled morning levels, but high evening levels
• High fasting or pre-dinner, but controlled PP or post dinner
• Controlled fasting or pre-dinner, but elevated PP or post
dinner
• All 4 parameters deranged
Insulin Dose adjustment
NEXT
117. Insulin Delivery Throughout Pregnancy
Initiating Insulin Therapy in GDM
• regular insulin based on specific abnormal FPG, pre-meal,
and 1-hour postprandial glucose readings
– high FPG with bedtime NPH
– pre-dinner hyperglycemia with pre-breakfast NPH
– bedtime hyperglycemia with pre-dinner NPH
– abnormal postprandial glucose with rapid-acting insulin (lispro or aspart)
immediately before the offending meal
• Evaluate regimen for 1 week; adjust as needed to maintain
glucose <90 mg/dL before meals and <120 mg/dL 1 hour
post-meal
• 1 unit of insulin will neutralize 20 mg/dl of blood sugar
Jovanovic L, ed in chief. Medical Management of Pregnancy Complicated by Diabetes. 3rd
ed. Alexandria, Va: American Diabetes Association; 2000:111-132
119. In patients who are not well controlled, a
brief period of hospitalization is often
necessary for the initiation of therapy
Individual adjustments to the regimens
implemented can then be made
Hospitalization
120. Clinical pearls
• Start with insulin @0.2Units per kg per day
• If type I DM need of basal insulin needs to be addressed
• If blood sugar highly elevated in GDM or Overt type II DM may start
with higher doses
• Long acting insulin at bedtime to cover morning fasting
• NPH dose must be adjusted based on fasting blood sugars
• Lantus offers a more constant basal coverage with less injections
121. Twice daily regimen
Hours of day
4:00 16:00 20:00 24:00
12:00
8:00
Plasma
insulin
24:00
Breakfast Lunch Dinner
122. Additional dose during lunch 4 tight control
Hours of day
4:00 16:00 20:00 24:00
12:00
8:00
Plasma
insulin
24:00
Breakfast Lunch Dinner
123. Split regimen
Regular Insulin before meal and long acting at bedtime
Hours of day
4:00 16:00 20:00 24:00
12:00
8:00
Plasma
insulin
24:00
Long act
Breakfast
Long act
Long act
Lunch Dinner
124. Insulin Lispro Controls Postprandial
Hyperglycemia in GDM
Plasma
glucose
(mg/dL)
Jovanovic L et al. Diabetes Care. 1999;22:1422-1427
0
20
40
60
80
100
120
140
0 60 120 180
Time (min)
Regular human insulin
Insulin lispro
125. Infant Malformations in Preexisting
Diabetes Are Related to First-Trimester
A1C Levels, Not Type of Insulin
A1C standard deviation from mean at first prenatal visit correlates with major anomaly rate in
insulin lispro–treated patients (5.4%, P=0.04)
Wyatt JW et al. Diabet Med [online early]. Available at: http://www.blackwell-synergy.com/
links/doi/10.1111/j.1464-5491.2004.01498.x/abs/
0
2
4
6
8
10
12
14
<–2 –2 to <0 0 to <2 2 to <4 4 to <6 6 to <8 8
Percent
with major
anomalies
A1C standard deviation from mean
127. KETOACIDOSIS
• As pregnancy is a state of relative insulin resistance
marked by enhanced lipolysis and ketogenesis
• diabetic ketoacidosis may develop in a pregnant woman
with glucose levels barely exceeding 200 mg/dl
• DKA may be diagnosed during pregnancy with minimal
hyperglycemia accompanied by a fall in plasma
bicarbonate and a pH value less than 7.30
128. clinical signs of volume depletion follow the
symptoms of hyperglycemia, which include
polydipsia and polyuria.
Malaise.
Headache.
nausea.
Vomiting.
KETOACIDOSIS
129. Occasionally, diabetic ketoacidosis may present in an
undiagnosed diabetic woman receiving β-mimetic
agents to arrest preterm labor
Because of the risk of hyperglycemia and diabetic
ketoacidosis in diabetic women
Terbutaline and magnesium sulfate has become the
preferred tocolytic for cases of preterm labor in these
cases.
Antenatal corticosteroids used to accelerate fetal lung
maturation can cause significant maternal
hyperglycemia and precipitate DKA
KETOACIDOSIS
130. An intravenous insulin infusion will usually be required
and is adjusted on the basis of frequent capillary
glucose measurements.
Therapy hinges on the meticulous correction of
metabolic and fluid abnormalities.
Every effort should therefore be made to correct
maternal condition before intervening and delivering
a preterm infant.
KETOACIDOSIS
131.
132. ANTEPARTUM FETAL EVALUATION
antepartum fetal monitoring tests are now used
primarily to reassure the obstetrician and
avoid unnecessary premature intervention.
These techniques have few false-negative
results, allowing the fetus to benefit from
further maturation in utero.
133. Ultrasound
Ultrasound is a valuable tool in
evaluating fetal growth, estimating
fetal weight, and detecting
hydroamnios and malformations.
134. Ultrasound….cont.
Ultrasound examinations should be
repeated at 4- to 6-week intervals to
assess fetal growth. The detection of
fetal macrosomia, the leading risk factor
for shoulder dystocia, is important in the
selection of patients who are best
delivered by cesarean section.
135. The non-stress test (NST (
• Done weekly from 28 weeks and Twice weekly
from 34 weeks
• remains the preferred method to assess ante-
partum fetal well-being in the patient with
diabetes mellitus
• If the NST is nonreactive, a biophysical profile
(BPP) or contraction stress test is then
performed .
136. Doppler umbilical artery velocimetry
Doppler umbilical artery velocimetry has been proposed as
a clinical tool for antepartum fetal surveillance in
pregnancies at risk for placental vascular disease.
It is found that Doppler studies of the umbilical artery may
be predictive of fetal outcome in diabetic pregnancies
complicated by vascular disease.
Elevated placental resistance as evidenced by an increased
systolic/diastolic ratio is associated with fetal growth
restriction and preeclampsia in these high-risk patients.
137.
138. Limited data from a single randomized
controlled trial suggest that induction of
labour in women with gestational diabetes
treated with insulin reduces the risk of
macrosomia.
The Cochrane Library, Issue 4, 2003
140. • Delivery by cesarean section usually is
favored when fetal distress has been
suggested by antepartum heart rate
monitoring
• Delivery planned at 38 weeks' gestation
• elbecause of poor control or a history of a
prior stillbirth, an elective delivery is
planned
141. During labor, continuous fetal heart rate
monitoring is mandatory. Labor is
allowed to progress as long as normal
rates of cervical dilatation and descent
are documented.
arrest of dilatation or descent despite
adequate labor should alert the
physician to the possibility of
cephalopelvic disproportion.
142. Indications:
1) Multipara with good obstretic history
2) Young primigravidae without any obstetric
abnormality
3) Presence of cong. Malformation of fetus.
Induction of labour:
143. • NO breakfast on the day of induction.
• Low rupture of membrane with simultaneous
oxytocin drip if no contraindication.
• 5% dextrose with 10 unit soluble insulin @ 100-
125ml /hr(1-1.25units /hr).
• Hourly bld glucose estimation using dextrostix
and insulin adjusted accordingly.
• If labour fails to start within 6-8 hrs or
unsatisfactory progress, Caesarian section.
Methods:
145. Indications:
1) Elderly primi
2) Multigravidae with BOH
3) Uncontrolled diabetes
4) Obstetrical complication like pre-
eclampsia,polyhydramnioius,malpresentation
5) Large baby
Caesarian section:
146. • Perform early morning.
• Omit breakfast and insulin dose.
• 5% dextrose with 10 units soluble insulin until
pt is able to take fluids by mouth.
• Insullin requirements suddenly falls following the
delivery.
• Epidural or spinal anaesthesia prefferd than GA
as oral feeding can be started soon.
147. • Usual dose of intermediate-acting insulin is given at
bedtime.
• Morning dose of insulin is withheld.
• Intravenous infusion of normal saline is begun.
• Once active labor begins or glucose levels fall below 70
mg/dl, the infusion is changed from saline to 5% dextrose
and delivered at a rate of 2.5 mg/kg/min.
• Glucose levels are checked hourly using a portable meter
allowing for adjustment in the infusion rate.
• Regular (short-acting) insulin in administered by intravenous
infusion if glucose levels exceed 140 mg/dl.
Insulin Management during Labor and Delivery
148. Scottish A national clinical guideline
• Women with insulin-requiring diabetes in pregnancies
which are otherwise progressing normally should be
assessed at 38 weeks gestation to ensure delivery by 40
weeks.
• Women with diabetes should be delivered in consultant-
led maternity units which have a senior physican,
obstetrician, and neonatologist available.
• The progress of labor should be monitored as for other
high risk women, including continuous electronic fetal
monitoring.
• Intravenous insulin and dextrose should be administered
as necessary to maintain blood glucose levels between 4
and 7 mmol/l.
149. • During labor close blood glucose monitoring
• Adjust dextrose and insulin accordingly
• post delivery spontaneos correction of GDM
• Screening for hypoglycemia of newborn
• Exclussive breast feeding
150. HAPO
(Hyperglycemia And Pregnancy Outcomes*)
Followed > 23,000 women after a 2-hour 75 gram GTT
to determine whether there were glucose value
thresholds that separated normal outcomes from
complicated outcomes.
Women with FBS > 105 or 2-hr glucoses > 200 were
unblinded.
Followed for BW > 90th percentile, primary cesarean,
neonatal hypoglycemia, cord-blood C-peptide > 90th
percentile.
*NEJM 2008;358:1991-2002
151. HAPO Conclusion
• Strong, continuous associations of maternal
glucose levels below those diagnostic of GDM
were seen with birthweight and increased
cord-blood C-peptide levels.
• The current criteria for diagnosing and
treating hyperglycemia during pregnancy
needs to be re-evaluated.
152. ACHOIS
(Australian Carbohydrate Intolerance
Study)
• Randomized 1000 women with 2-hr 75 gram glucose
values 140-200 to treatment – no treatment (‘normal
< 155).
• Treatment group: Fewer serious perinatal
complications and lower birth weights but more
NICU admissions.
• Number needed to treat to prevent a ‘serious
complication’ (death, shoulder dystocia, bone
fracture, nerve palsy) was 34.
• No change in cesarean rate.
NEJM 2005;352:2477-86
153. Gestational Diabetes: Post-natal
• Blood glucose testing first few days after
delivery
• Fasting glucose rechecked 6-12 weeks
following delivery
• Every 6-12 months thereafter to be screened
for Type 2 Diabetes-high risk of developing
Type 2 Diabetes (7x higher) and/or CVD
Kitzmiller, et al Diabetes Care 30:S225-S235, 2007
Diabetes Care 34:Supplement 1, 2011
154. Why is Gestational Diabetes a Concern
AFTER Pregnancy
• Immediately after pregnancy, 5% to 10% of women with GDM
have diabetes, usually type 2.
• Women who had hGDM have 35% to 60% chance of
developing diabetes in the 10 to 20 years after delivery.
• Risk for cardiovascular disease may be increased.
• Children of GDM pregnancies may be at greater risk for future
obesity and diabetes.
Buchanan TA, et al.Diabetes Care 2007; 30 Suppl 2: S105-11.
Kitzmiller JL, et al. Diabetes Care 2007; 30 Suppl 2: S225-35.
155. Postpartum Focus:
– OGTT (6 weeks to 6 months 75 g OGTT)
– weight management,
– postpartum visit with a registered dietitian
– Encourage breastfeeding
– Monitoring occasionally with meter
– Future pregnancy
156. Neonatal Hypoglycemia Is Inversely Related to
Maternal Hyperglycemia at Delivery
0
50
100
150
200
250
Maternal glucose Neonatal glucose
Type 1 diabetes
Type 2 diabetes
GDM
Jovanovic L, Peterson CM. Am J Med. 1983;75:607-612
Glucose
(mg/dL)
157. Postpartum Considerations
Lactation and Nutrition
• Breastfeeding is recommended
– Decreased risk of type 1 diabetes and infection
in infant, Decrease incidence of type 2 by ½.
– Promotes infant growth and development
• Maintain pregnancy meal plan or develop postpartum plan
to meet added caloric requirements of breastfeeding
• Rapid weight loss is not advised; exercise is recommended
• Insulin use must be continued if postpartum
normoglycemia cannot be maintained with MNT
• Women with previous GDM have
– 40% to 60% risk of developing type 2 diabetes in 5 to 15 years
– 66% risk of GDM in future pregnancies
158. Breastfeeding and DM meds
• Both metformin and glyburide/glipizide are
found at low concentrations (or not at all) in
breast milk
– Hale et al, Diabetologia 2002
– Feig et al, Diabetes Care 2005
– Can be considered however, more long-term
studies needed
159. Contraception
Type % Effectiveness Acceptability Notes
Oral
contraception
94–98 +
Use preparations with
<0.35-mg estrogen
Norplant
Depo-Provera
96–99 –
May increase insulin
needs and/or lower
glucose tolerance
Barrier methods 72–88 + High failure rates
Intrauterine
devices
97 +
Risk of infection no
higher with diabetes
Rhythm 80 –
Menstrual irregularity
may lead to failure
Tubal ligation 99+ + Potentially irreversible
Adapted from Jovanovic L, ed in chief. Medical Management of Pregnancy Complicated
by Diabetes. 3rd ed. Alexandria, Va: American Diabetes Association; 2000:21-28
160. Birth Weight and Risk of Future Type 2 Diabetes
0
5
10
15
20
25
2500 g 3500 g 4500 g
Birth weight
Percent
1500 g
Jovanovic L. Diabetes Care. 2000;23:1219-1220
McCance DR et al. BMJ. 1994;308:942-945
3 lb, 5 oz 5 lb, 8 oz 7 lb, 11 oz 9 lb, 14 oz
161. • Gestational diabetes is a common problem .
• Risk stratification and screening is essential in almost all
pregnant women
• Tight glycemic targets are required for optimal maternal and
fetal outcome
• Patient education is essential to meet these targets
• Long term follow up of the mother and baby is essential
Conclusion
167. Primary prevention strategies
• Preconception
– Educate that pregnancy can be a risk factor
– Infections/inflammation
– Screen for diabetes and its risk factors in the
potential mother
169. – Infancy and childhood
• Nutrition of the infant
• Monitor growth and well-being
• Legislation to promote good dietary environment
• Physical activity
• Risk assessment and lifestyle modification
• Initiate nutrition, physical activity and stress reduction
programmes in educational institutions and the
community
170. – Adult life
• Screening for high risk individuals
• Proper nutrition
• Encourage physical activity
• Stress in adult life
• Promote employer and employee education
• Increased awareness and education
throughout the ‘‘Life Circle’’
• Secondary prevention strategies
– Multi-factorial/multi-disciplinary/multi-sectoral
approach to care
– Access to quality essential medicines to all
Notas do Editor
Even though gestational diabetes is, by definition, diabetes diagnosed during pregnancy, sometimes blood glucose levels do not return to normal after delivery. Even if glucose levels do return to normal after pregnancy, a history of gestational diabetes (hGDM) has a lifelong impact on the mother’s risk for developing diabetes. Immediately after pregnancy, 5% to 10% of women with gestational diabetes are found to have diabetes, usually type 2.Women who had GDM have a 35% to 60% chance of developing diabetes in the 10 to 20 years after delivery.Children of GDM pregnancies may be at greater future risk for obesity and diabetes.Also, the risk for cardiovascular disease is increased in women with a history of GDM. Studies in women with prior GDM suggest that a chronic inflammatory response may be present and represents an early feature of the cluster of CVD risk factors that relate to insulin resistance and the metabolic syndrome. The good news is there are steps a woman can take to prevent or delay diabetes and lower that risk for both herself and her child. And we learned this from the Diabetes Prevention Program or D-P-P which was sponsored by NIH. Buchanan TA, Xiang A, Kjos SL, Watanabe R: What is gestational diabetes? Diabetes Care 2007; 30 Suppl 2: S105-11.Kitzmiller JL, Dang-Kilduff L, Taslimi MM: Gestational diabetes after delivery. Short-term management and long-term risks. Diabetes Care 2007; 30 Suppl 2: S225-35.