Gestational Diabetes: Update in Diagnosis and Management

Gestational Diabetes
Update in Diagnosis and Management

Objectives
 Review basic physiology of gestational diabetes
 Review fetal and maternal implications
 Review current recommendations for screening for
GDM
 Review 3 important studies published within last 5
years that are driving current recommendations
 Review recommendations from the 5th International
Workshop-Conference on Gestational Diabetes
Mellitus
 Review use of insulin analogs in pregnancy
 Review use of oral antihyperglycemic agents in
pregnancy
Brief overview
 Defined as carbohydrate intolerance that

begins or is first recognized during
pregnancy
 Important because it impacts maternal
health care both during and after pregnancy
 Incidence varies, but most often reported as
5-7% of pregnant women; may be greater
in some high-risk populations
Brief overview
Insulin Resistance
Insulin Output
Normal pregnancy
12 24 36
Gestational Age (weeks)
Brief overview
Insulin Resistance
Insulin Output
Gestational diabetes
12 24 36
Gestational Age (weeks)
Brief overview
 Underlying risk factors include

increased maternal age, obesity, h/o
GDM in prior pregnancy, h/o large
babies
 Increased risk for development of
hypertensive disorders, cesarean
delivery, and developing diabetes later
in life
Brief overview
Maternal hyperglycemia
Fetal hyperglycemia
Fetal hyperinsulinemia
Pederson Hypothesis
(1952)
Brief overview
 Fetal risks include adverse events

related to macrosomia, ie, shoulder
dystocia and birth injuries, neonatal
hypoglycemia and hyperbilirubinemia
 As rates of obesity increase, so do the
rates of type 2 diabetes and GDM
Current recommendations
for screening for GDM
 Depends on who you ask!!
– ADA
– ACOG
– WHO
– 4th International Workshop-Conference on GDM
– National Diabetes Data Group
– United States Preventive Services Task Force
– 5th International Workshop-Conference on GDM
 Do risk assessment at first visit, with no
screening for low risk
– Low-risk ethnicity (Caucasian, European)
– Age < 25
– BMI < 25
– No known diabetes in first degree relative
– No h/o glucose intolerance
– No h/o obstetric complications usually associated
with GDM
4 International Workshop-
th
Conference on Gestational
Diabetes Mellitus, ADA, ACOG
 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 4th International Workshop-
 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
2-hr or 3-hr 100-g OGTT
 Threshold value for 1-hr GCT is 130 or 140
– either is acceptable
 Threshold values for 3-hr OGTT are 95, 180,
155, 140, respectively; 2 values must be
abnormal to diagnose GDM
4th International Workshop-
 WHO advocates universal screening utilizing
a one-step 2-hr 75-g OGTT
 Patient is diagnosed with GDM if fasting >
126 or 2-hr > 140
 5th International Workshop-Conference on
Gestational Diabetes Mellitus did not change
recommendations set forth by 4th
International Workshop-Conference on
Gestational Diabetes Mellitus
Effect of Treatment of Gestational Diabetes
Mellitus on Pregnancy Outcomes. Crowther,
CA et al. NEJM, June 2005.
 Hypothesis: Treatment of women

with GDM will reduce the risk of
perinatal complications
 Prospective, randomized study of
1,000 women with GDM (490 in
intervention group, 510 in routine-care
group)
*Often referred to as Australian Carbohydrate Intoleranc Study (ACHOIS)

 Eligible women had the following:

– Singleton or twin pregnancy
– One or more risk factors for GDM or
positive 50-g glucose challenge test (>
140)
– 75-g glucose-tolerance test at 24-34
weeks with fasting glucose < 140 and
glucose at 2 hours was 140-198*
*When study was initiated, women meeting this criteria were classified as having
glucose intolerance of pregnancy by WHO, but in 1998 WHO classified any
glucose level above normal as indicative of GDM
 Intervention group:
– Individualized dietary advice
– Self-monitored blood glucose levels 4x/day
– Insulin therapy for FBS > 99 or 2-hr postprandial
> 126
 Routine-care group:
– Providers unaware of diagnosis of glucose
intolerance
– Care c/w clinical care in which screening for
GDM is not available
Mellitus on Pregnancy Outcomes. Crowther, CA
et al. NEJM, June 2005.
Outcome Intervention
Group
Routine-
Care Group
Adjusted P
value
Infants
Total Number 506 524
Serious perinatal 7 (1%) 23 (4%) 0.04

complications
Women
Total Number 490 510
Labor induction 189 (39%) 150 (29%) <0.001
Cesarean delivery 152 (31%) 164 (32%) 0.73

Mellitus on Pregnancy Outcomes. Crowther, CA
et al. NEJM, June 2005.
Conclusions
 Treatment of women with GDM (glucose
intolerance) reduced the rate of serious
perinatal complications from 4% to 1%
 Number needed to treat to prevent serious
complication was 34
 Benefits were associated with increased rate
of labor induction, but not an increased rate
of C/S
Hyperglycemia and Adverse Pregnancy
Outcomes (HAPO). NEJM. May, 2008.
 Hypothesis: maternal hyperglycemia

less severe than overt DM will still
increase risk for adverse pregnancy
outcomes
 25,505 pregnant women at 15 centers
in 9 countries underwent 75-g oral
glucose-tolerance testing at 24-32
weeks gestation
 Data remained blinded if FBS < 105 and 2-

hr glucose was < 200
 Only women whose data were blinded and
who did not undergo any additional glucose
testing outside the HAPO study were
included for analysis
 Primary outcomes were BW > 90th
percentile, primary C/S, clinically diagnosed
hypoglycemia, and cord-blood serum C-
peptide > 90th percentile (fetal
hyperinsulinemia)
 Secondary outcomes were delivery

before 37 weeks, shoulder dystocia or
birth injury, need for NICU,
hyperbilirubinemia, and preeclampsia
Glucose categories defined:
2-hr <90 91- 109- 126- 140- 158- >178

108 125 139 157 177
1-hr <105 106- 133- 156- 172- 194- >212
132 155 171 193 211
FBS <75 75-79 80-84 85-89 90-94 95-99 >100
1 2 3 4 5 6 7
HAPO. NEJM. May 2008: Frequency of primary
outcomes across the Glucose Categories
Birth weight > 90th percentile

30
25
Frequency (%)
20
Fasting
15
1-hr glu
10 2-hr glu
0
1 2 3 4 5 6 7
Glucose category
Cord-Blood Serum C-Peptide > 90th Percentile

35
30
25
Frequency (%)
20 Fasting
15 1-hr glu
2-hr glu
10
5
0
1 2 3 4 5 6 7
Glucose category
Primary Cesarean Section

35
30
25
Frequency (%)
20 Fasting
15 1-hr glu
2-hr glu
10
5
0
1 2 3 4 5 6 7
Glucose category
Clinical Neonatal Hypoglycemia

5
4.5
4
Frequency (%)
3.5
3
Fasting
2.5
1-hr glu
2
2-hr glu
1.5
1
0.5
0
1 2 3 4 5 6 7
Glucose category
Outcomes (HAPO). NEJM, May, 2008.
Conclusions
 With increasing maternal glucose levels, the
frequency of each primary outcome
increased, although less so for clinical
neonatal hypoglycemia than for the others
 Secondary outcomes of preeclampsia,
shoulder dystocia or birth injury, premature
delivery, NICU admit, and
hyperbilirubinemia also showed significant
positive associations with maternal glycemia
Summary and Recommendations of the Fifth
International Workshop-Conference on Gestational
Diabetes Mellitus. Diabetes Care. July 2007
 Efforts at diagnosis and management of GDM are

supported (preferably with onset of treatment by
30 weeks gestation)
 Identification and intensive management of GDM is
associated with a decrease in mortality and
morbidity in infants
 With appropriate therapy, the likelihood of IUFD is
not detectably higher than in the general population
 Morbidity, however, can be increased and will likely
remain an issue until optimal management of the
altered intrauterine environment is understood and
appropriate interventions are implemented
Diabetes Mellitus. Diabetes Care. July 2007.
Goals and surveillance
 Maternal glycemia
– Target glucose concentrations:
 FBS < 96
 1 hr PP < 140
 2 hr PP < 120
– Daily SMBG using meters appears to be

superior to less frequent monitoring in
the clinic
Goals and surveillance
 Assessment of fetal response utilizing

ultrasound measurements, particularly
of fetal abdomen, in second and early
third trimesters can provide useful
information
 Less intensified management may be
allowed with normal growth (fetal AC
< 75th percentile for GA)
MNT and physical activity
 Medical nutrition therapy remains

cornerstone of treatment for GDM;
however, relatively little information
available to allow evidence-based
recommendations regarding specific
nutritional approaches such as total
calories and nutrient distribution to the
management of GDM
MNT and physical activity
 MNT best prescribed by registered dietician

 Food plans should be culturally appropriate
 Adjust amount and type of carbohydrate to
achieve target for PP glucose concentrations
 No data on optimal weight gain for women
with GDM
 Physical activity of 30 min/day is
recommended for individuals capable of
participating
Intensified medical therapy
 Insulin remains cornerstone in

treatment of patients who fail to
maintain glycemic goals with MNT
 Insulin analogs offer advantages of
improved glucose control with
immunogenic rates similar to human
insulin
 Rapid-acting insulin analogs (RAIA)

– Lispro (Humalog) and Aspart (Novolog)
– Achieve more rapid insulin peak and have been
shown to provide better post-prandial glucose
control
– Multiple studies have demonstrated improved PP
glucose control with RAIA vs human regular
insulin with no increased risk of complications,
such as retinopathy or teratogenic effect
 Long-acting insulin analogs

– Glargine (Lantus) and Detemir (Levomir)
– Lantus provides peak-less duration of
action around 24 hrs, translating to less
glucose variability and lower risk of
nocturnal hypoglycemia
– Levomir also with peak-less but less
longer duration of action, about 12 hrs;
provides similar benefits as Lantus
 Long-acting insulin analogs: safety

– Currently classified as Category C by FDA
 Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and
there are no controlled studies in women, or studies in women and animals are not available. Drugs should be
given only if the potential benefit justifies the potential risk to the fetus.
 Compares to NPH which is Category B and is onlybasal insulin that has received FDA approval for treating
GDM specifically
– Review article Nov 2007: “long-acting insulin

analogs do not yet have sufficient safety
evaluation in clinical studies to warrant their use
during pregnancy”
– Recent placental perfusion study published in
Mar 2010 showed Lantus does not cross the
human placenta
 Oral antihyperglycemic agents

– Glyburide acts by promoting production
of insulin in the pancreas
– Langer, et al. NEJM 2000: Randomized,
prospective study comparing glyburide
and insulin in women with GDM
– Conclusion: In women with GDM,
glyburide is a clinically effective
alternative to insulin therapy.

 Oral antihyperglycemic agents
– Metformin is thought to act by inhibiting liver’s
production of glucose; appears to increase
insulin sensitivity/reduce insulin resistance
– Rowan, et al. NEJM 2008: Randomized,
prospective study comparing metformin and
insulin in GDM
– Conclusion: In women with GDM, metformin
(alone or with supplemental insulin) is not
associated with increased perinatal complications
as compared with insulin. The women preferred
metformin to insulin treatment.
Obstetric management
 Fetal surveillance
– Ultrasound screening for congenital anomalies
recommended for women with GDM who present
with A1C > 7.0% or FPG > 120
– Data insufficient to determine whether
surveillance beyond self-monitoring of fetal
movements is indicated in women with GDM
who continue to meet targets of glycemic control
with MNT regimens alone and in whom fetal
growth is normal
 Maternal surveillance
– Risk for PTD may be increased with untreated GDM
– Use of steroids to enhance fetal lung maturity should not
be withheld because of GDM but intensified monitoring of
glucose levels is indicated with possible need for
(increased) insulin
– Risk for hypertensive disorders increased with GDM
– Blood glucose monitoring should be continued during labor
with insulin or glyburide as necessary to correct maternal
hyperglycemia
 Timing and route of delivery

– No data supporting delivery of women
with GDM prior to 38 weeks in absence of
objective evidence of maternal or fetal
compromise
– Lung maturity amnio not indicated in
well-controlled patients who have
indications for induction or C/S as long as
reasonable certainty of dates
 Timing and route of delivery

– Delivery of LGA fetus in setting of GDM is
associated with increased risk of birth
injury compared with nondiabetic
population
– Strategies to reduce this risk include
liberal policy toward C/S; however, no
controlled trials available to support this
approach
Post partum/long term
 Studies show that after GDM, 35-60%

of women develop Type 2 diabetes
within 10 years
 Glucose tolerance testing should be
performed 6-12 weeks after delivery in
GDM women who do not have
diabetes immediately PP
 Optimal testing frequency for diabetes
long term has not been established
A Multicenter, Randomized Trial of Treatment
for Mild Gestational Diabetes. Landon, MB, et
al. NEJM, Oct 2009.
 Hypothesis: Treatment of mild GDM

improves pregnancy outcomes.
 Prospective, randomized study of 958
women (485 in treatment group, and 473 in
control group)
 Treatment group received nutritional
counseling, diet therapy, and insulin if
required
 Control group received usual prenatal care
al. NEJM, Oct 2009.
 Eligible women had the following:

– Abnormal 1-hr 50-g glucose challenge
with glucose between 135-200
– Abnormal 3-hr GTT with FBS < 95 and 2
of 3 glucose measurements that
exceeded thresholds for 1-hr (180), 2-hr
(155), or 3-hr (140)
al. NEJM, Oct 2009.
 Primary outcome was composite

outcome that included perinatal
mortality, hypoglycemia,
hyperbilirubinemia, neonatal
hyperinsulinemia, and birth trauma
al. NEJM, Oct 2009.
 Neonatal secondary outcomes included

BW > 4000 gm, LGA, SGA, NICU
admit, and RDS
 Maternal secondary outcomes included
weight gain, gestational HTN,
preeclampsia, cesarean delivery, labor
induction, and shoulder dystocia
al. NEJM, Oct 2009.
Outcome Treatment Control Group P value

variable Group (N=485) (N = 473)
GA at birth (wk) 39.0 38.9 0.87
Composite end 32.4% 37% 0.14

point
al. NEJM, Oct 2009.
Neonatal Treatment Control Group P value
Secondary Group (N=485) (N=473)
Outcome Variable
Birth weight 3302 gm 3408 gm <0.001
BW > 4000 gm 5.9% 14.3% <0.001
LGA 7.1% 14.5% <0.001
Preterm delivery 9.4% 11.6% 0.27
SGA 7.5% 6.4% 0.49
NICU admit 9.0% 11.6% 0.19
RDS 1.9% 2.9% 0.33

al. NEJM, Oct 2009.
Maternal Treatment Control Group P value

Secondary Group (N=476) (N=455)
Outcome Variable
Induction of labor 27.3% 26.8% 0.86
Cesarean delivery 26.9% 33.8% 0.02
Shoulder dystocia 1.5% 4.0% 0.02
Preeclampsia/HTN 8.6% 13.6 0.01
BMI at delivery 31.3 32.3 <0.001
Weight gain (kg) 2.8 5.0 <0.001

al. NEJM, Oct 2009.
Conclusions
 Although treatment of mild GDM did
not reduce the frequency of the
composite primary outcome, it did
lower the risks of fetal overgrowth,
shoulder dystocia, cesarean delivery,
and preeclampsia
Summary
 Screening/diagnosis
– No new guidelines at present
– WHO endorses universal screening with
single step, arguing that the 2-step
process introduces additional barrier to
care
– Discussions continue around use of
fasting, random glucose, or A1C at initial
visit, but no consensus at present
Summary
To diagnose overt diabetes (preexisting) in pregnancy
Measure of glycemia Threshold

Fasting glucose > 126 mg/dl
A1C > 6.5%
Random glucose > 200 mg/dl
International Association of Diabetes

and Pregnancy Study Groups, 2009
Summary
Diagnosis of GDM (75-g OGTT)
Glucose measure Glucose threshold

FPG 92 mg/dl
1-hr plasma glucose 180 mg/dl
2-hr plasma glucose 153 mg/dl
*One or more of these values must be met or exceeded for
diagnosis of GDM
Summary
 First prenatal visit
– Measure FPG, A1C, or random glucose on all or only high-
risk women
 If results indicate overt diabetes as per Table 1, treat and f/u
as for preexisting diabetes
 If results are not diagnostic of overt diabetes and FPG > 92
but < 126, diagnose as GDM; if FPG < 92, test for GDM at
24-28 weeks
 24-28 weeks
– 2-hr 75-g OGTT after overnight fast on all women not
previously found to have overt diabetes or GDM
– Overt diabetes if FPG > 126
– GDM if one or more values equals or exceeds thresholds
– Normal if all values on OGTT less than thresholds
Summary
 Medical management of GDM includes
following:
– Nutritional therapy
– Exercise
– Self-monitoring of glucose at home
– If diet and exercise fail, oral hyperglycemic
agent or insulin
 Glyburide “preferred” but metformin safe
 Short-acting insulin analogs should be standard, and
long-acting analogs not far behind, if not already here
– Goal: Euglycemia!!
Summary
2-hr <90 91- 109- 126- 140- 158- >178

108 125 139 157 177
1-hr <105 106- 133- 156- 172- 194- >212

132 155 171 193 211
FBS <75 75-79 80-84 85-89 90-94 95-99 >100
1 2 3 4 5 6 7
Summary
 Fetal surveillance with GDM
– Increased surveillance of fetal well-being
suggested if oral agent or insulin necessary, or
abnormal fetal growth evident on ultrasound
– Optimal timing of delivery remains uncertain, but
would consider delivery by 39 weeks if evidence
of poor glucose control and/or abnormal fetal
growth noted
– Allow usual indications for delivery management
if diet controlled with normal growth and well-
being
Summary
 Postpartum management
– Assess fasting and/or 2-hr PP in first day or two
after delivery – no further treatment necessary if
normal (majority of GDM)
– If fasting and/or 2-hr PP abnormal, continue oral
agent or insulin
– Screen for Type 2 diabetes at 6-week
postpartum visit
– Council patients regarding dietary and behavioral
changes necessary to minimize risk of
developing overt diabetes later in life
Summary
Metabolic assessments after GDM
Time Test Purpose

Post-delivery (1-3 d) Fasting or random glucose Detect persistent, overt
diabetes
Postpartum visit 75-g 2-h OGTT PP classification of glucose
metabolism per ADA
1 year postpatum 75-g 2-h OGTT Assess glucose metabolism
Annually Fasting plasma glucose Assess glucose metabolism
Tri-annually 75-g 2-h OGTT Assess glucose metabolism
Prepregnancy 75-g 2-h OGTT Assess glucose metabolism
5th Annual Workshop-Conference on GDM

Gestational Diabetes: Update in Diagnosis and Management

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Gestational Diabetes

Update in Diagnosis and Management

 Defined as carbohydrate intolerance that

 Underlying risk factors include

 Fetal risks include adverse events

 Hypothesis: Treatment of women

*Often referred to as Australian Carbohydrate Intoleranc Study (ACHOIS)

 Eligible women had the following:

Total Number 506 524

Serious perinatal 7 (1%) 23 (4%) 0.04

Total Number 490 510

Labor induction 189 (39%) 150 (29%) <0.001

Cesarean delivery 152 (31%) 164 (32%) 0.73

 Hypothesis: maternal hyperglycemia

 Data remained blinded if FBS < 105 and 2-

 Secondary outcomes were delivery

Glucose categories defined:

2-hr <90 91- 109- 126- 140- 158- >178

Birth weight > 90th percentile

Cord-Blood Serum C-Peptide > 90th Percentile

Primary Cesarean Section

Clinical Neonatal Hypoglycemia

 Efforts at diagnosis and management of GDM are

Goals and surveillance

– Daily SMBG using meters appears to be

Goals and surveillance

 Assessment of fetal response utilizing

MNT and physical activity

 Medical nutrition therapy remains

MNT and physical activity

 MNT best prescribed by registered dietician

Intensified medical therapy

 Insulin remains cornerstone in

Intensified medical therapy

 Rapid-acting insulin analogs (RAIA)

Intensified medical therapy

 Long-acting insulin analogs

Intensified medical therapy

 Long-acting insulin analogs: safety

– Review article Nov 2007: “long-acting insulin

Intensified medical therapy

 Oral antihyperglycemic agents

Intensified medical therapy

 Timing and route of delivery

 Timing and route of delivery

Post partum/long term

 Studies show that after GDM, 35-60%

 Hypothesis: Treatment of mild GDM

 Eligible women had the following:

 Primary outcome was composite

 Neonatal secondary outcomes included

Outcome Treatment Control Group P value

Composite end 32.4% 37% 0.14

BW > 4000 gm 5.9% 14.3% <0.001

LGA 7.1% 14.5% <0.001

Preterm delivery 9.4% 11.6% 0.27

SGA 7.5% 6.4% 0.49

NICU admit 9.0% 11.6% 0.19

RDS 1.9% 2.9% 0.33

Maternal Treatment Control Group P value

Cesarean delivery 26.9% 33.8% 0.02

Shoulder dystocia 1.5% 4.0% 0.02

Preeclampsia/HTN 8.6% 13.6 0.01