16 July 2009

Fetal outcomes: Comparison of gestational diabetes



Fetal outcomes: Comparison of oral agents with diet controlled and insulin controlled gestational diabetes
By:Amanda Hatton, MD
Investigators
* Amanda Hatton, MD
* Selman Welt, MD
* Samuel Prien, PhD

Background
* 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
* Fetal hyperglycemia leads to fetal hyperinsulinemia which has detrimental consequences to fetal growth and well-being2
* 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
* Glycemic monitoring, dietary regulation and medical therapy are used to control diabetes and prevent postnatal sequelae
* 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
* To compare fetal outcomes in mothers with gestational diabetes treated with:
* Diet - ADA diet, weight dependent, 3 meals and 3 snacks
* Oral agents
* 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
* 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
Materials and Methods
* Review mother’s and infant’s charts to compare outcomes of different treatment modalities
* 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
* Continuous data will be evaluated with an analysis of variance (ANOVA)
* Discrete data will be evaluated with a Chi-Square or Mann-Whitney U test
Results
* 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

Fetal outcomes: Comparison of gestational diabetes.ppt

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Ultrasonographic features of endometrium



Ultrasonographic features of endometrium in pre- and postmenopausal women
By:C. Tracy Suit, MD
Cornelia de Riese, MD
Samuel Prien, PhD
Kelsey Kelso, BS

Background

* The endometrium is a dynamic tissue
o Menstrual cycle
o Postmenopausal
o Exogenous hormones

Transvaginal US
* Non-invasive
* Relatively inexpensive
* Good safety profile
* Readily available

Normal endometrium
* Menstrual phase
* Proliferative phase
* Secretory phase
* In the follicular phase, the endometrium becomes relatively hypodense
* As the cycle progresses the endometrium becomes more hyperechoic
* Ovulatory period = trilaminar endometrium
* Usually disappears 48 hours after ovulation
* Postmenopausal women
* A small amount of fluid may be considered normal

Premenopausal—Differential Diagnosis
* Often due to normal proliferation under hormonal influences
* Can include:
o Polyps
o Polypoid growths
o Hyperplasia or cancer
o Submucosal fibroids
Postmenopausal
* Important distinction: symptoms
* Exogenous hormones
Postmenopausal—differential diagnosis
* Polyps
* Hyperplasia or cancer
* Fibroids
Associated sonographic findings
* Polyps: cystic spaces
* Hyperplasia: regular/homogeneous echotexture
* Cancer: irregular margins, indistinct borders between the endometrium and myometrium, heterogeneous echotexture, complex fluid

Study objective
* To evaluate the predictive value of endometrial thickness and descriptive sonographic appearance on pathology in pre- and postmenopausal women
Methods
* 1903 gynecologic ultrasounds of the endometrium were performed between January, 2004 and January 2009
* Stratification: Of these, 367 had pathology performed within 3 months of the ultrasound
* The patients were then divided into either pre- or post menopausal after review of the chart
* Each US was critically evaluated for:
o Endometrial thickness
o Descriptors of the endometrium
Exclusion criteria
* No corresponding pathology (EMB, curettage, or hysterectomy) within 3 months of the US
* No measurement of the endometrial thickness or distortion by fibroids so that the endometrium could not be meaningfully evaluated
* Patient less than 18 years old
Methods
* Pathology was classified into groups:
o Benign: proliferative or secretory, atrophic, or chronic endometritis
o Precancerous or cancerous: simple hyperplasia with or without atypia, complex hyperplasia with or without atypia, endometrial cancer
Statistics
* Endometrial descriptors were compared with pathology using a Chi-Square analysis
* Endometrial thickness and age were compared using a Student’s t-test
Results
Result: Postmenopausal group
Results: Premenopausal group
Conclusions
* Confirmed that endometrial thickness is increased in pathological conditions such as hyperplasia and cancer
* But hyperplasia was diagnosed often within the “normal” ranges, especially in the premenopausal women
* In the postmenopausal group, complex hyperplasia and cancer were diagnosed with an endometrial thickness of 3 and 5 mm, respectively
* In premenopausal women, the average endometrial thickness in women with pathology was still in the normal range for secretory endometrium
* In addition, no simple hyperplasia was diagnosed in the postmenopausal group—when pathology was found, it was much more likely to have become frank cancer
* Heterogeneity and irregularity in echo pattern were significantly more likely to be associated with hyperplasia or cancer in the premenopausal group. It may have not reached significance in the postmenopausal women due to the smaller sample size.
* One weakness of the study is the low rate of pathology
* DO THE EMB in symptomatic women
OUTLOOK

* What can the sonohysterogram add?
* We need to correlate findings to ethnicity, metabolic and exogenous as well as endogenous hormonal influences to further define high risk scenarios.

Ultrasonographic features of endometrium in pre- and postmenopausal women.ppt

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General Internal Medicine Lectures



General Internal Medicine Lectures in ppt format from
Texas Tech University Health Sciences Centre School of Medicine

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