Fetal outcomes: Comparison of
oral agents with diet controlled
and insulin controlled gestational
diabetes
Amanda Hatton, MD
Investigators
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Amanda Hatton, MD
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Selman Welt, MD
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Samuel Prien, PhD
Background
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Gestational diabetes affects from 1-14% of
pregnant mothers1
Levels of diabetogenic placental steroids and
peptide hormones (estrogen, progesterone,
chorionic sommatomammotrophin) rise linearly
throughout the second and third trimester
resulting in progressively increasing tissue
resistance to insulin2
Maternal insulin resistance requires a significant
increase in pancreatic insulin production to more
than twice non-pregnant levels
Failure to adequately compensate for increased
demand of insulin production leads to maternal
hyperglycemia followed by fetal hyperglycemia
Fetal health implications
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Fetal hyperglycemia leads to fetal
hyperinsulinemia which has detrimental
consequences to fetal growth and well-being2
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Promotes storage of excess nutrients leading to
macrosomia
Drives catabolism of oversupply of fuel, using energy
and depleting fetal oxygen stores
Episodic fetal hypoxia leads to increased adrenal
catecholamines causing hypertension, cardiac
remodeling, and hypertrophy
Hypoxia also causes stimulation of erythropoietin
which in turn increases hematocrit level and causes
poor circulation and postnatal hyperbilirubinemia
At birth fetal hyperinsulinemia in absence of maternal
glucose supply leads to hypoglycemia
Treatment of GDM
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Glycemic monitoring, dietary regulation and
medical therapy are used to control diabetes and
prevent postnatal sequelae
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Insulin discovered in 1922, successful management of
diabetic pregnancies became possible and the
frequency of antepartum fetal death decreased by
one half2
Glycemic control must be instituted early and
aggressively if excellent newborn outcome is to be
achieved
Oral agents such as acarbose and glyburide are
aimed at augmenting insulin supply, decreasing
insulin resistance, and limiting postprandial
hypoglycemia
These agents have been shown to be an effective and
safe alternative, since they do not significantly cross
the placenta in vitro3
Objectives
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To compare fetal outcomes in mothers with
gestational diabetes treated with:
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Diet - ADA diet, weight dependent, 3 meals and 3
snacks
Oral agents
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Acarbose - alpha-glucosidase inhibitor, reversibly inhibits
enzymes in the small intestine, delaying cleavage of
oligosaccharides and disaccharides to monosaccharides
Glyburide - sulfonylurea compound, stimulates insulin release
from the pancreatic beta cells, reduces glucose output from
the liver and also increases insulin sensitivity at peripheral
target sites
Insulin – weight based split mix dose of NPH and
Novolog, insulin pump therapy, or long acting insulin
with supplementation
This study was submitted to the IRB and was
found to be exempt from formal IRB review
Experimental Design
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Retrospective chart review
Identify mothers seen at Texas Tech Health Science
Center (Lubbock) with gestational diabetes who were
treated and delivered between January, 2005 and
January, 2008
Includes pregestational diabetics and those diagnosed by
random blood sugar >200mg/dL or at least two
abnormal values on a 3 hour 100g glucose challenge
All patients were provided with diabetic education,
including nutrition guidance at the onset of their prenatal
care in the case of preexisting diabetes or soon after
diagnosis
General Treatment Guidelines
Diet
Fasting or preprandial >100 mg/dL, 20%
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Glyburide 5-10mg daily
Postprandials >120 mg/dL, 20%
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Acarbose 25-100mg TID with meals
Still uncontrolled
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Insulin
*control = fasting/preprandials
<90 mg/dL, 80%, postprandial <120 mg/dL, 80%
Materials and Methods
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Review mother’s and infant’s charts to compare
outcomes of different treatment modalities
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Class of gestational diabetes
Treatment and changes in treatment
Level of control
Complications of pregnancy
Mode of delivery
Fetal weight
Delivery complications
Fetal complications (hypoglycemia,
hyperbilirubinemia, respiratory distress)
Patients diagnosed ≥ 36 weeks gestation will be
excluded
Statistical Analysis
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Continuous data will be evaluated with an
analysis of variance (ANOVA)
Discrete data will be evaluated with a ChiSquare or Mann-Whitney U test
Results
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We expect to find similar fetal outcomes in
diabetic mothers with blood glucose levels
that are well controlled by diet, oral
agents or insulin
Thus far we have noted that there are no
noticeable differences in outcomes
pending a greater number of chart
reviews and statistical analysis
References
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1. American College of Obstetrics and
Gynecologists—Practice Bulletin Number 30
Gestational Diabetes, Washington, September
2001.
2. Moore TR, Creasy RK, Resnik R: Diabetes in
Pregnancy. Maternal-Fetal Medicine 53, pp.
964-985. W.B. Saunders Company, 1999.
3. Klieger C, Pollex E, Koren G. (2008) Treating
the mother—protecting the unborn: The safety
of hypoglycemic drugs of pregnancy. J Mat
Fetal Neonatal Med 21(3), pp. 191-196.