Transcript insulin

INSULIN THERAPY
FOR GDM
M.M. Ebrahimi , MD
Endocrinology Center
Taleghani Hospital
20-7-85
INDICATIONS
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Approximately 15 percent of women
with GDM are placed on insulin therapy
With diet , 75 - 80 percent of women
with GDM will achieve normoglycemia
main purpose of drug intervention at
these levels is to minimize the incidence
of macrosomia
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INDICATIONS
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target glucose levels are exceeded
despite dietary therapy
when FBG is 90 mg/dL or
1h pp BG is 120 mg/dL on two or more
occasions within a two-week interval
despite dietary therapy
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INDICATIONS
ACOG & ADA recommend:
administration of insulin when :
 FBG > 95 mg/dL (PG >105 )
or
 1h pp BG >130 to 140 mg/dL ( PG >155 )
or
 2h-pp BG > 120 mg/dL ( PG > 130 )
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Dose of insulin
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Varies in different populations
but the majority of studies have
reported a total insulin dose ranging
from 50 to 90 units to achieve glucose
control
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Calculation of dose
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If insulin is required because the FBS is
high, an intermediate-acting insulin,
such as NPH insulin, is given qhs
initial dose : 0.2 U/kg
Eg : 0.2u * 70kg = 14 u
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Calculation of dose
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If postprandial BS are high :regular
insulin or insulin lispro before meals
1.5 U per 10 gr CHO in the breakfast
meal
1 U per 10 gr CHO in the lunch and
dinner meals
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Calculation of dose
If both preprandial and postprandial
blood glucose are high
four injection per day regimen
 0.7 U/kg up to week 18
 0.8 U/kg for weeks 18 to 26
 0.9 U/kg for weeks 26 to 36
 1.0 U/kg for weeks 36 to term
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Calculation of dose
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In a morbidly obese woman, the
initial doses of insulin may need to be
increased to 1.5 to 2.0 units/kg to
overcome the combined insulin
resistance of pregnancy and obesity
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INSULIN
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insulin is divided :
45% as NPH insulin (30% before
breakfast and 15% hs)
55% as preprandial regular insulin
(22% before breakfast, 16.5% before
lunch, and 16.5% before dinner)
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Initial calculation of insulin for
4 injections a day
Fraction of total insulin dose
Time
NPH
regular
prebreakfast
5/18
2/9
prelunch
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1/6
Predinner
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1/6
HS
1/6
_
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Eg : 0.7u * 51 kg = 36 u
Fraction of total insulin dose
Time
NPH
regular
prebreakfast
5/18=10
2/9=8
prelunch
_
1/6=6
Predinner
_
1/6=6
HS
1/6=6
_
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INSULIN
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A four-times daily regimen improved
glycemic control and perinatal
outcome compared to a twice-daily
regimen
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Titration of insulin dose
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Based upon frequent SMBG
4 or more glucose measurements each
day are needed to optimize therapy and
ensure a smooth increase of insulin as insulin
requirements increase with pregnancy
progression.
Twin gestations have an approximate
doubling of the insulin requirement
throughout pregnancy
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Goals
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FBS / PM BG : 60 – 90 mg/dl
1hr pp : < 120 mg/dl
3AM : 60 – 100 mg/dl
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Acute hypoglycemia
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Acute hypoglycemia remote from meal or
snack time
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treated by 10 to 20 g of carbohydrate
immediately
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also use a correction factor of one unit of
rapid-acting insulin lowers blood
glucose by 25 mg/dL
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Acute hypoglycemia
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For glucose <50 mg/dL, subtract
two units of regular insulin from the
dose of insulin given before the meal
for glucose 50 to 75 mg/dL, we
subtract one unit from the dose of
insulin given before the meal
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Titration of insulin dose
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for glucose 75 to 100 mg/dL do not
change insulin dose
for glucose 100 to 125 mg/dL add
one unit regular insulin to the dose of
insulin given before the meal
for glucose 100 to 150 mg/dL, add
two units regular insulin to the dose
of insulin given before the meal
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Not recommended use of
insulin pumps
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insulin pumps are expensive and
Do not clearly provide a benefit in
the setting of GDM
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Type of insulin
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The three rapid acting insulin analogs
(lispro, aspart, glulisine) are
comparable in immunogenicity to
human Regular insulin, but only lispro
and aspart have been investigated
in pregnancy and shown to have
acceptable safety profiles, minimal
transfer across the placenta, and
no evidence of teratogenesis
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Type of insulin
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lispro and aspart insulin analogs both
improve postprandial excursions
compared to human Regular
insulin and are associated with lower
risk of delayed postprandial
hypoglycemia
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Type of insulin
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Long-acting insulin analogs (insulin glargine,
insulin detemir) have not been studied
extensively in pregnancy
use human NPH insulin as part of a
multiple injection regimen in pregnant women
Lente insulins are not recommended due
to variability of effect
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INTRAPARTUM MANAGEMENT
Spontaneous labor
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Insulin is required during the latent
phase of labor
SQ or IV insulin infusion with a goal :
blood glucose 70 - 90 mg/dL
One method :1-3 U/h
N/S may be sufficient to maintain
euglycemia when labor is anticipated
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Spontaneous labor
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active labor : insulin resistance rapidly decreases
and insulin requirements fall rapidly
Thus, continuing insulin therapy is likely to lead to
hypoglycemia
To prevent this, glucose should be infused at a rate
of 2.55 mg/kg per min
Capillary blood glucose : q1h
glucose infusion should be doubled for the next
hour if the blood glucose value is < 60 mg/dL
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Spontaneous labor
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BG 120 mg/dL or greater require the
administration of rapid-acting insulin analogues
SQ or regular insulin intravenously until the
blood glucose value falls to 70 to 90 mg/dL
At this time, the insulin dose is titrated to maintain
normoglycemia while glucose is infused at a rate of
2.55 mg/kg per min
Bolus doses of glucose should not be given
because they can raise maternal blood glucose
concentrations and increase the risk of neonatal
hypoglycemia, fetal hypoxia, and fetal or neonatal
acidosis
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Cesarean delivery
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bedtime NPH insulin dose may be
given on the morning of surgery and
q8h thereafter if surgery is delayed
D10W if PG < 60 mg / dl
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Induction
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If induction procedure is judged likely
to be lengthy , 25 – 30 % of
morning insulin as NPH may be
administered especially if the mother
will be allowed meals during early labor
If BG >110 mg / dl :use insulin
drip
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postpartum
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BG should be measured on the day
after delivery to ensure that the
mother no longer has hyperglycemia,
using criteria established for
nonpregnant individuals
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POSTPARTUM MANAGEMENT
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Insulin requirements drop sharply after
delivery since expulsion of the
fetoplacental unit leads to cessation of
production of placental growth hormone
and placental lactogen, which have
short half-lives
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Oral anti-hyperglycemic
agents
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The ADA and ACOG do not approve
the use of oral anti-hyperglycemic
agents during pregnancy
Not been approved by the Unites
States FDA
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Tolbutamide and
chlorpropamide
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No tolbutamide or chlorpropamide
(older sulfonylureas) as therapy of
GDM because these drugs cross the
placenta and
can cause fetal hyperinsulinemia,
which can lead to macrosomia and
prolonged neonatal hypoglycemia
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Glyburide
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In contrast to older sulfonylureas,
transplacental passage of glyburide
appears to be minimal and is not
associated with an excess of neonatal
hypoglycemia. Several reports have
suggested that glyburide is a safe and
effective treatment of GDM, and its use is
becoming more prevalent
The fifth International Workshop cautioned its
use until there is more research
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Glyburide
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The only large, randomized study of glyburide
therapy in pregnancy included 404 women
with mild GDM who were randomly
assigned to receive glyburide or insulin
The mean blood glucose concentration during
treatment was 105 mg/dL in both groups,
and there were no differences in the
frequency of macrosomia, neonatal
hypoglycemia, and other neonatal
morbidity or cord serum insulin
concentrations
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Oral Hypoglycemic agents
Glyburide
Achieved N BG
LGA infants
Macrosomia
C Section
Hypoglycemia
Preeclampsia
Anomalies
Insulin
82%
12%
7
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88%
13%
4
24
9
6
2
6
6
2
Langer NEJM 2000
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Glyburide
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Glyburide is not recommended as
Rx of women with GDM until its safety
and efficacy have been more firmly
established
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Metformin
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no randomized trials evaluating the use of
metformin in women with GDM
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Several observational series have reported
generally good outcomes with use of metformin in
pregestational diabetics
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Currently, there is a large trial in Australia that will
be completed in 2007
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Until then, metformin should not be used
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Acarbose
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an alpha glucosidase inhibitor,
is poorly absorbed from the gastrointestinal
tract.
studies have suggested efficacy in reducing
postprandial glucose excursions in GDM, but
with the expected frequency of abdominal
cramping
Since a small proportion of this drug may be
absorbed systemically, further study should
evaluate potential transplacental passage
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Thiazolidinediones,
glinides, and GLP-1
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Use of thiazolidinediones, glinides, and GLP-1
during pregnancy is considered experimental
There are no controlled data available in
pregnancy
One study reported that rosiglitazone crossed
the human placenta at 10 to 12 weeks
gestation, fetal tissue levels were about half
of maternal serum levels
Ex vivo human placental perfusion studies of
GLP-1 agonists detected minimal levels on the
fetal side (fetal:maternal ratio 0.017)
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