This document discusses diabetes during pregnancy, including pregestational and gestational diabetes. Pregestational diabetes includes type 1 and type 2 diabetes and increases risks for maternal and fetal complications like congenital malformations. Gestational diabetes develops during pregnancy due to insulin resistance and increases risks for the mother and child. Screening and treatment aim to control blood glucose levels and minimize risks.
2. Diabetes during pregnancy can be divided into pregestational and
gestational diabetes
Pregestational diabetes
it may be divided into type 1 and type 2 and genetic diabetic syndromes
PREVALENCE —
• Pregestational diabetes complicates 1 to 2 percent of all pregnancies
• it accounts for 13 to 21 percent of diabetes in pregnancy
• The prevalence in women of reproductive age is increasing
• in reproductive-aged women, type 2 diabetes is becoming more prevalent
and is more common than type 1 diabetes in some populations
3. pregestational diabetes carry a significantly elevated risk of adverse maternal and fetal outcomes, including
congenital malformations ( limited to pregestational and not pure gestational DM)
macrosomia
preeclampsia,
polyhydramnios
miscarriage,
preterm delivery,
operative delivery
shoulder dystocia, brachial plexus injury
perinatal mortality
Fetal organomegaly (hepatomegaly, cardiomegaly)
Neonatal respiratory problems and metabolic complications (hypoglycemia, hyperbilirubinemia, hypocalcemia, erythremia)
tight glycemic control in the periconception period and throughout pregnancy is associated with improved outcomes
The first weeks of pregnancy are particularly important because congenital malformations induced by hyperglycemia develop during this period
(called diabetic embryopathy) ,early glycemia correlates with late pregnancy outcomes, including macrosomia, preeclampsia, and perinatal
mortality
4. • Pregnancy-induced metabolic and vascular changes can also affect
glycemic control and development or progression of diabetes
complications
• women with type 2 diabetes dose not have better perinatal outcomes
(major congenital malformations, perinatal mortality) than those with type
1 diabetes and have the same rate of complications
• Women with type 1 diabetes are at higher risk of developing severe hypo-
and hyperglycemia, including DKA.
• The intense medical and lifestyle regimen that must be undertaken before
and during pregnancy and worry over pregnancy outcome can have a
significant impact on the diabetic woman's psychological well-being
5. Congenital malformations
• Rates of major congenital malformations in women with type 1 diabetes range
from 4-5 % compared with 5-7% in women with type 2 diabetes versus 2 percent
at the nondiabetic population
• periconceptional hyperglycemia is associated with the high end of the range
• types of major congenital anomalies observed in women with pregestational
diabetes are similar to those in women without diabetes and include congenital
heart defects, neural tube defects, limb defects, and orofacial clefts except sacral
agenesis is more common in diabetic
6. growth restriction Uncommonly, pregestational diabetes is associated with failure of
the fetus to achieve its genetic growth potential especially in type 1 diabetic women
Maternal medical risks
Diabetic retinopathy
• The majority of women with diabetic retinopathy will not experience worsening of
retinopathy during or following pregnancy .
• for some, particularly those with proliferative retinopathy retinopathy may worsen during
pregnancy and persist after delivery
• rapid tightening of glycemic control has been associated with worsening retinopathy in
women with pregestational diabetes
• In most women, the benefits of normoglycemia for the fetus far outweigh the modest and
generally transient deterioration in retinopathy from improved glycemic control, as milder
forms of diabetic retinopathy typically improve after delivery
7. Diabetic kidney disease
• Women with diabetes, moderately increased albuminuria (formerly
microalbuminuria), and normal kidney function are at low risk for loss of kidney
function during pregnancy
• Among women with overt proteinuria at baseline, urinary protein excretion can rise
dramatically as pregnancy progresses and resolve after delivery
• In contrast, women with poorly controlled hypertension or reduced glomerular
filtration rate (GFR) and heavy proteinuria (serum creatinine level >1.5 mg/dL,
proteinuria >3 grams in 24 hours) at the onset of pregnancy are at risk of permanent
kidney damage, including end-stage kidney disease
8. Cardiovascular disease — Pregnant women with pregestational
diabetes are at increased risk of macrovascular cardiac disease
(coronary artery disease, heart failure, stroke) and microvascular
cardiovascular disease (microvascular angiopathy, cardiac autonomic
neuropathy.
Gastroparesis
Severe gastroparesis is one of the few relative contraindications to pregnancy
in women with pregestational diabetes as it can lead to extreme hypo- and
hyperglycemia, increased risk of diabetic ketoacidosis (DKA), weight loss and
malnutrition.
Diabetic ketoacidosis — Diabetic ketoacidosis (DKA) is more common, occurs
at lower levels of glycemia, and carries a higher risk of mortality
The risk of fetal demise is substantial: rates of 9 to 35 percent have been
reported.
9. mangment
● Prior to pregnancy, all women of childbearing age with diabetes should be Counseled
about the impact of glycemic status on maternal-fetal outcome, the risk of development or
progression of preexisting complications of diabetes, and the types and risks of adverse
maternal, fetal, and neonatal outcomes.
●Helping the patient who wish to become pregnant to achieve good glucose control, with A1c
in the normal range if possible the primary preconception A1c goal for all women with
diabetes is <6.5 percent, but attempt to achieve A1c <6 percent if this is possible without
inducing significant hypoglycemia and fasting capillary blood glucose concentration from 80 to
110 mg/dL (4.4 to 6.1 mmol/L) and two hour postprandial glucose concentration <155 mg/dL
(8.6 mmol/L). women with diabetes should be encouraged to allow a minimum of six months
to achieve optimal glucose control before trying to conceive, if they are not already well
controlled
10. ●Adjusting medications as needed for fetal safety
●Folic acid 400 micrograms/day is recommended for most
reproductive-age women
●Evaluating for comorbidities and complications of diabetes
●Initiating treatment of comorbidities and complications or
optimizing status of existing medical conditions
●women at risk of deteriorating renal function leading to
dialysis may decide not to become pregnant
11. Gestational DM
Pregnancy is accompanied by insulin resistance, mediated primarily by placental
secretion of diabetogenic hormones including growth hormone, corticotropin-releasing
hormone, human placental lactogen (most important ), and progesterone. These and
other metabolic changes ensure that the fetus has an ample supply of nutrients.
Gestational diabetes develops during pregnancy in women whose pancreatic function is
insufficient to overcome the insulin resistance associated with the pregnant state
terms such as "overt diabetes" or "diabetes mellitus during pregnancy is to describe
diabetes diagnosed by standard nonpregnant criteria prior to conception or early in
pregnancy when the effects of insulin resistance are less prominent
12. the term "gestational diabetes" is used to describe diabetes diagnosed during the
second half of pregnancy,
The term "gestational diabetes" is also used to describe glucose levels in early
pregnancy that do not meet standard nonpregnant criteria for overt diabetes but are
diagnostic for gestational diabetes
Prevalence — The prevalence of diabetes during pregnancy is about 10 to 20 percent .
The prevalence varies worldwide and among racial and ethnic groups, generally in
parallel with the prevalence of type 2 diabetes. The incidence is higher in Native
American, Pacific Islander, and South or East Asian women and in the middle east
including Iraq. Prevalence also varies because of differences in screening practices,
population characteristics (eg, average age and body mass index [BMI] of pregnant
women), testing method, and diagnostic criteria.
Prevalence has been increasing over time, possibly due to increases in mean maternal
age and weight
13. women with gestational diabetes are at increased risk of
developing type 2 diabetes, as well as type 1 diabetes
and cardiovascular disease
Their adolescent and adult offspring are also at risk of
long-term sequelae, such as obesity, abnormal glucose
tolerance, or metabolic syndrome and increased risk of
autism unrelated to genetic cuases but due to
intrauterine environmental conditioning
14. Risk factors — Pregnant women with any of the following characteristics is at increased risk of developing gestational diabetes; the
risk increases when multiple risk factors are present
●Personal history of impaired glucose tolerance or gestational diabetes in a previous pregnancy
●Member of one of the following ethnic groups, which have a high prevalence of type 2 diabetes: Hispanic-American, African-
American, Native American, South or East Asian, Pacific Islander middle easterians
●Family history of diabetes, especially in first degree relatives [40]
● BMI >30 kg/m2, significant weight gain in early adulthood and between pregnancies [41], or excessive gestational weight gain
during the first 18 to 24 weeks [42-44]
●Maternal age >25 years of age
●Previous unexplained perinatal loss or birth of a malformed infant
●Glycosuria at the first prenatal visit
●Medical condition/setting associated with development of diabetes, such as metabolic syndrome, polycystic ovary syndrome
(PCOS), current use of glucocorticoids, hypertension
●Multiple gestation and age above 40
15. Preventive approaches for risk reduction — In overweight and obese
women, weight loss before pregnancy can reduce the risk of developing
gestational diabetes
Exercise should be started before pregnancy or soon thereafter, performed
three to four times per week for 30- to 60-minute sessions, and continued until
delivery
a healthy diet and smoking cessation before pregnancy are healthy behaviors
that may be associated with reduced risk of developing gestational diabetes
16. screening and diagnosis
In the United States, universal screening or testing appears to be the most practical approach because 90
percent of pregnant women have at least one risk factor for glucose impairment during pregnancy and
risk factors are poor predictors of women who had an abnormal glucose tolerance test
Timing of screening/testing
testing can be performed as early as the first prenatal visit if there is a high degree of suspicion that the
pregnant woman has undiagnosed type 2 diabetes
women with a prior history of gestational diabetes have a 50 percent risk of recurrence in subsequent
pregnancies
In the absence of early testing or if early testing is negative, universal screening is performed at 24 to 28
weeks of gestation
17. 1 step aproch ( NICE guidelines ,WHO)
75 gm 2 hours glucose tolerance test (more sensitive)
1 abnormal reading diagnostic of GDM
2 steps approach (ACOG)
50-gram one-hour glucose screen
after 1 hour If above 200 mg/dl diagnostic of gestational diabetes
if above 135 -200 mg /dl go to
100gm 3 hours glucose tolerance test
2 abnormal values to diagnose diabetes
HBA1c
No threshold for glycated hemoglobin (A1C) in the second and third trimesters had both good
sensitivity and specificity as a screening test for gestational diabetes.
A positive urine dipstick for glycosuria is not sensitive or specific
18. World Health Organization (WHO) thresholds for positive two-hour 75-gram oral GTT (2013). A diagnosis of
"gestational diabetes mellitus" is made when one or more of the following glucose thresholds is met any
time during pregnancy.
Fasting 92 to 125 mg/dL (5.1 to 6.9 mmol/L)
OR
One-hour ≥180 mg/dL (10.0 mmol/L)
OR
Two-hour 153 to 199 mg/dL (8.5 to 11.0 mmol/L)
19. Diagnostic criteria for the 100-gram three-hour GTT to diagnose gestational diabetes
mellitus
Plasma or serum glucose level
Carpenter/Coustan
Plasma level
National Diabetes Data
Group
mg/dL mmol/L mg/dL mmol/L
Fasting 95 5.3 105 5.8
One hour 180 10.0 190 10.6
Two hours 155 8.6 165 9.2
Three hours 140 7.8 145 8.0
20. ACOG two step approach for screening and diagnosis of gestational diabetes
Step one
1. Give 50-gram oral glucose load without regard to time of day
2. Measure plasma or serum glucose
3. Glucose ≥135 mg/dL (7.5 mmol/L) or ≥140 mg/dL (7.8 mmol/L) is elevated and requires administration of a 100-gram
oral glucose tolerance test*. The lower threshold provides greater sensitivity, but would result in more false positives
and would require administering the full glucose tolerance test to more patients than the 140 mg/dL threshold. The
lower threshold should be considered in populations with higher prevalence of gestational diabetes.
Step two
1. Measure fasting serum or plasma glucose concentration
2. Give 100-gram oral glucose load
3. Measure plasma or serum glucose at one, two, and three hours after glucose load
4. A positive test is generally defined by elevated glucose concentrations at two or more time points (either Carpenter
and Coustan thresholds or National Diabetes Data Group thresholds can be used).
In 2017, ACOG stated that even one abnormal value may be used for the diagnosis of GDM.
21. ADA criteria for the diagnosis of diabetes
1. A1C ≥6.5%. The test should be performed in a laboratory using a method that is NGSP certified and
standardized to the DCCT assay.*
OR
2. FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least eight hours.*
OR
3. Two-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during an OGTT. The test should be performed as described
by the World Health Organization, using a glucose load containing the equivalent of 75-gram anhydrous glucose
dissolved in water.*
OR
4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200
mg/dL (11.1 mmol/L).
22. World Health Organization (WHO) thresholds for positive two-hour 75gram oral GTT
(2013). A diagnosis of "gestational diabetes mellitus" is made when one or more of the
following glucose thresholds is met any time during pregnancy.
Fasting 92 to 125 mg/dL (5.1 to 6.9
mmol/L)
OR
One-hour ≥180 mg/dL (10.0 mmol/L)
OR
Two-hour 153 to 199 mg/dL (8.5 to 11.0
mmol/L)
23. Management
Monitoring of blood glucose
• frequent daily self-monitoring of blood glucose (SMBG)
1.Fasting 2. pre meal 3. 1 and 2 hours post meals 4. at bed time 5. 3-4 oclock AM
• periodic measurement of hemoglobin A1C at - initial visit and each trimester
• ultra sound examination for macrosomia by measuring fetal abdominal circumference
Target blood glucose values — (ACOG) and the (ADA) recommend
●Fasting glucose concentrations ≤95 mg/dL (5.3 mmol/L)
●Preprandial glucose concentrations ≤100 mg/dL (5.6 mmol/L)
●One-hour postprandial glucose concentrations ≤140 mg/dL (7.8 mmol/L)
●Two-hour postprandial glucose concentrations ≤120 mg/dL (6.7 mmol/L)
●During the night, glucose levels ≥60 mg/dL (3.3 mmol/L)
Nice guidelines also recommend similar values
24. The target A1C level is below 6.5 in preconception period and <6 percent throughout
pregnancy
NICE guidelines recommend against the use of HBA1c to monitor diabetic control during pregnancy
Choice of therapy
• Women with type 2 diabetes who have good glycemic control with medical nutritional therapy
alone can remain on this therapy during pregnancy
• Women on insulin therapy should continue insulin during pregnancy
• Women using continuous subcutaneous insulin infusion (insulin pump) effectively pre pregnancy
can continue this therapy. avoid initiating pump therapy during pregnancy
• For women with excellent glycemic control on an oral anti-hyperglycemic drug such as metformin
at conception, can continue taking metformin safely and effectively and take supplemental
insulin later in pregnancy as required
25. Exercise
• maternal benefits, including minimizing weight gain, improving glycemic control,
• fetal benefits include potential reduction in fetal adiposity
In the absence of contraindications, 30 or more minutes of moderate intensity, low-fall-risk physical activity can be
performed by women on most days of the week
Dietary management
Avoid excessive weight gain to be limited to the recommended pregnancy weight gain,Weight loss in pregnancy is not
generally recommended, except for the very obese
Caloric requirements for a singleton pregnancy are increased by an average of approximately 300 kcal/day above basal daily
needs in nonpregnant women in second trimester and 450 kcal/day in third trimester ,no increase in calories is
recommended for the first trimester
Distribution
Breakfast – 10 to 20 percent of total calories.
●Lunch – 20 to 30 percent of total calories.
●Dinner – 30 to 40 percent of total calories.
●Snacks – Up to 30 percent of total calories. Snacking is based on caloric needs and support for hypoglycemia as well as
consideration of prepregnancy BMI, as overweight and obese women may not need to snack. Bedtime snacks are often
needed to minimize nocturnal hypoglycemia.
26. Recommendations for total and rate of weight gain during pregnancy by
prepregnancy BMI
Total weight gain
Rates of weight gain* second and
third trimester
Prepregnancy BMI
Range in kg Range in lb Mean (range) in
kg/week
Mean (range)
in lb/week
Underweight (<18.5 kg/m2) 12.5 to 18 28 to 40 0.51 (0.44 to 0.58) 1 (1 to 1.3)
Normal weight (18.5 to
24.9 kg/m2)
11.5 to 16 25 to 35 0.42 (0.35 to 0.50) 1 (0.8 to 1)
Overweight (25.0 to 29.9 kg/m2) 7 to 11.5 15 to 25 0.28 (0.23 to 0.33) 0.6 (0.5 to 0.7)
Obese (≥30.0 kg/m2) 5 to 9 11 to 20 0.22 (0.17 to 0.27) 0.5 (0.4 to 0.6)
27. Oral anti diabetic agents
Metformin
Women with diabetes may be advised to use metformin[2] as an adjunct or alternative to insulin in the preconception period
and during pregnancy, when the likely benefits from improved blood glucose control outweigh the potential for harm. All
other oral blood glucose-lowering agents should be discontinued before pregnancy and insulin substituted
glibenclamide
Consider glibenclamide for women with gestational diabetes:
in whom blood glucose targets are not achieved with metformin but who decline insulin therapy or
who cannot tolerate metformin ,
glyburide appears to be associated with higher rates of neonatal hypoglycemia and macrosomia than metformin
the American Diabetes Association consensus statement advises discontinuation of these agents prior to pregnancy but
cautions against doing so in the first trimester since metabolic control may be disrupted during the transition glyburide can be
used in special circumstances
28. insulins
Short acting
Rapid acting insulins are the recommended short acting insulins to be used during
pregnancy
Prevent postprandial glycemic excursion and delayed postprandial hypoglycemia
lispro, aspart
• investigated in pregnancy
• comparable in immunogenicity to human regular ,insulin,
• have acceptable safety profiles,
• minimal transfer across the placenta
• no evidence of teratogenesis
29. Long acting insulins
NPH –
• well known safety and efficacy
• doses can be adjusted frequently and quickly
Insulin Detemir
Well studied during pregnancy and approved safty
Can be given once or twice daily
Insulin Glargin
Not studied well during pregnancy
Have high affinity to IGF-1 receptor -Teratogenicity ?
-stimulate growth and
Macrosomia
Long acting insulin so dose not carry the flexibility needed in insulin dosing
during pregnancy and day and night basal needs difference
30. Pharmacokinetics of the most commonly used insulin preparations
Insulin type
Onset of
action
Peak effect
Duration of
action
Lispro, aspart, glulisine 5 to 15 minutes 45 to 75 minutes Two to four hours
Regular About 30 minutes Two to four hours Five to eight
hours
NPH About two hours 4 to 12 hours 18 to 28 hours
Insulin glargine About two hours No peak 20 to >24 hours
Insulin detemir About two hours Three to nine
hours
6 to 24 hours*
NPL About two hours Six hours 15 hours
Insulin degludec About two hours No peak >40 hours
31. Insulin dosing
The usual daily insulin requirement in pregnant women with type 1 diabetes is
• 0.7 units/kg in the first trimester,
• 0.8 units/kg for weeks 13 to 28,
• 0.9 units/kg for weeks 29 to 34, and
• 1.0 units/kg for weeks 35 to term
Type 2 diabetes patients have variable insulin requirement
Dosing
Approximately 50 percent of the total insulin dose is administered as a rapid acting insulin (eg, lispro or
aspart) before each meal and the other 50 percent is administered as an intermediate insulin (NPH) twice
daily
After delivery
the patient should undergo after 6 weeks GTT , FBS messurment is a reasonable alternative
