insulin therapy for gdm m.m. ebrahimi, md endocrinology center taleghani hospital 20-7-85
TRANSCRIPT
INSULIN THERAPY FOR GDM
M.M. Ebrahimi , MD Endocrinology CenterTaleghani Hospital20-7-85
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INDICATIONS 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
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
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
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
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
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
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 doseTime NPH regularprebreakfast 5/18 2/9prelunch _ 1/6Predinner _ 1/6HS 1/6 _
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Eg : 0.7u * 51 kg = 36 u
Fraction of total insulin doseTime NPH regularprebreakfast 5/18=10 2/9=8prelunch _ 1/6=6Predinner _ 1/6=6HS 1/6=6 _
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INSULIN
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 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
FBS / PM BG : 60 – 90 mg/dl 1hr pp : < 120 mg/dl 3AM : 60 – 100 mg/dl
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Acute hypoglycemia Acute hypoglycemia remote from meal
or snack time treated by 10 to 20 g of carbohydrate
immediately 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
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 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
insulin pumps are expensive and
Do not clearly provide a benefit in the setting of GDM
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Type of insulin 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
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 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
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 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 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
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
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
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
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
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
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 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
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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Glyburide Insulin
Achieved N BG 82% 88%LGA infants 12% 13%Macrosomia 7 4C Section 23 24Hypoglycemia 9 6Preeclampsia 6 6Anomalies 2 2
Oral Hypoglycemic agents
Langer NEJM 2000
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Glyburide
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
no randomized trials evaluating the use of metformin in women with GDM
Several observational series have reported
generally good outcomes with use of metformin in pregestational diabetics
Currently, there is a large trial in Australia that will be completed in 2007
Until then, metformin should not be used
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Acarbose 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 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)