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Definition
Gestational diabetes (GDM) is defined as glucose intolerance of variable degree with onset or first recognition during the present pregnancy. It can be screened by drawing a 1-hour glucose level following a 50-g glucose load, but is definitively diagnosed only by an abnormal 3-hour OGTT following a 100-g glucose load.
Importance
The growth and maturation of the fetus are closely associated with the delivery of maternal nutrients, particularly glucose. This is most crucial in the third trimester and is directly related to the duration and degree of maternal glucose elevation. Thus, the negative impact is as highly diverse as the variety of carbohydrate intolerance that women bring to pregnancy.
For the mother with GDM there is a higher risk of hypertension, preeclampsia, urinary tract infections, cesarean section, and future diabetes. Many of the problems associated with overt diabetic pregnancies can be seen in infants of gestational diabetic pregnancies, such as macrosomia, neural tube defects, neonatal hypoglycemia, hypocalcemia, hypomagnsemia, hyperbilirubinemia, birth trauma, prematurity syndromes, and subsequent childhood and adolescent obesity.
Prevalence
The prevalence of GDM varies worldwide and among different racial and ethnic groups within a country. The variability is partly because of the different criteria and screening regimens (i.e., not all pregnant women are screened). Studies using a 100-g 3-hour OGTT and either the criteria of the National Diabetes Data Group (NDDG) or of Carpenter and Coustan have found prevalence rates of 1.4% to 12.3% in the United States, respectively.
Pathophysiology
Gestational diabetes is pathophysiologically similar to type II diabetes. Approximately 90% of the persons identified have a deficiency of insulin receptors (prior to pregnancy) or a marked increase in weight that has been placed on the abdominal region. The other 10% have deficient insulin production and will proceed to develop mature-onset insulin-dependent diabetes.
HPL blocks insulin receptors and increases in direct linear relation to the length of pregnancy. Insulin release is enhanced in an attempt to maintain glucose homeostasis. The patient experiences increased hunger due to the excess insulin release as a result of elevated glucose levels. This insulin release further decreases insulin receptors due to elevated hormonal levels.
Diagnostic Criteria and Screening Procedures
The traditional method of screening for GDM is to assess risk factors: age, pre-pregnancy weight, family history of diabetes in a first-degree relative, previous large baby, and previous perinatal loss. Unfortunately, screening based solely on risk factors will only identify approximately 50% of women with GDM.
Glucosuria is a common finding in pregnancy due to increased glomerular filtration and is therefore unreliable as a diagnostic finding.
The ADA (American Diabetes Association) recommend that all pregnant women, who have not been identified with glucose intolerance earlier in pregnancy, be screened with a 50-g 1-hour GCT between 24 and 28 weeks of pregnancy. Such test can be performed at anytime of the day and with disregard to previous meal ingestion.
A value equal to or above 140 mg/dL should be used as the threshold level and indicates the need for a 100-g 3-hour OGTT. For the OGTT, the patient is fasting and receives 100-g of glucose after a fasting glucose level is obtained. A blood sample is taken every hour for 3 hours. The patient is advised to sit quietly during the test to minimize the impact of exercise on glucose levels.
The glucose values used to detect gestational diabetes were first determined by O'Sullivan (1964) in a retrospective study designed to detect risk of developing type II diabetes in the future. The values were set using venous whole blood and required 2 values reaching or exceeding the value to be positive. Subsequent information has led to alteration in O'Sullivan's criteria. For example: when methods for blood glucose determination changed from the use of whole blood to venous plasma samples, the criteria for GDM were also changed once whole blood glucose values are lower than plasma levels due to glucose uptake by hemoglobin (NDDG, 1979).
Since the adoption of the NDDG criteria, more specific glucose oxidase or hexokinase tests for glucose determination have replaced older methods, and new threshold values have been calculated by Carpenter and Coustan. Sacks and co-workers also have shown that correction of the O'Sullivan's cutoffs may be necessary and suggested new cutoff values in 1989.
Oral Glucose Tolerance Test (100 g)
Values For The Diagnosis of Gestational Diabetes (mg/dL)
O' Sullivan NDDG (1979) Carpenter & Coustan (1982) Sacks et al (1989) Fasting 90 105 95 96 1 hour 165 190 180 172 2 hour 145 165 155 152 3 hour 125 145 140 131
If one abnormal value is seen during the 100-g 3-hour OGTT it is recommended that the test be repeated approximately 1 month later. There is growing evidence that 1 abnormal value is sufficient to make an impact on the health of the fetus and is now the criterion used by most clinicians to initiate treatment. In a study of 106 women with one abnormal value on the OGTT, 34% were diagnosed with GDM when the test was repeated 1 month later, emphasizing the importance of repeat testing when only one abnormal value is found.
OBS (Obstetrics/Obstetricians): If GDM and fetal macrosomia begin to develop in the first trimester, then a diagnostic test to identify women at risk for GDM and to predict infants at risk for macrosomia should be accurate in the first trimester.
Medical Management
The reason for lowering the glucose level to a normoglycemic one is to prevent diabetic complications. The goal of medical management of women with GDM, therefore, is to prevent perinatal morbidity and mortality by normalizing the level of glycemia and other metabolites (i.e., lipids and amino acids) to the levels of non-diabetic pregnant individuals.
Dietary Therapy
Nutritional counseling is the mainstay of therapy for the gestational diabetic woman. The optimal dietary prescription would be one that provides the calories and nutrients necessary for maternal and fetal health, results in normoglycemia, prevents ketosis, and results in appropriate weight gain.
One of the difficulties with dietary prescription for women with GDM is the difference between lean and obese women. Obese women with GDM may benefit from a low calorie diet and weight reduction to reverse the metabolic disturbances, but proper nutrition is needed to assure fetal growth and development.
Jovanovic and Peterson found the following diet to result in euglycemia: 30 kcal/kg/24h present pregnant weight for normal-weight women, 24 kcal/kg/24h for overweight women (120%-150% ideal body weight), 12 to 15 kcal/kg/24h for morbidly obese women (>150% ideal body weight), and 40 kcal/kg/24h for underweight women (<80% ideal body weight). They recommend that the diet be composed of 40% to 50% carbohydrate, 20% to 25% protein, and 30% to 40% fat (polyunsaturated).
The patient checks her glucose 4 times daily (eg., fasting,and 1-hour postprandial breakfast, lunch, dinner). The desired values are a fasting of <90 mg/dL and a 1-hour <130 mg/dL. The average glucose levels should be ~90. After she has obtained a good understanding of her diet and the glucose values are in the desired range, she can decrease the frequency of testing to 3 days per week chosen randomly.
Insulin Therapy
If diet is not successful in maintaining relative euglycemia, then insulin therapy is recommended. To identify the women who will require insulin, circulating glucose levels should be monitored at frequent intervals. The ADA and ACOG (American College of Obstetricians and Gynecologists) recommend glucose measurements be taken both fasting and after meals to 1 to 2-week intervals. Insulin therapy should be initiated if the fasting glucose levels exceed 105 mg/dL and/or if the 2-hour postprandial levels exceed 120 mg/dL on two or more occasions within a 2-week interval.
Several centers, however, use the 1-hour time point because it reflects the peak glycemic response to a meal. Two studies have found that the 1-hour postprandial glucose level was a better predictor of infant birth weight than the fasting level. For this reason, when the fasting blood glucose level is 90 mg/dL or more, or the 1-hour postprandial glucose is 120 mg/dL or more on two or more glucose measurements within 1 or 2 weeks, then insulin therapy is initiated. Several regimens are possible for insulin therapy. Jovanovic and Peterson suggest the regimen seen in the tables below.
Initial Calculation of Insulin
7:30 am 4:30 pm 10:00 pm Type NPH Regular
Total
8/18 I
4/18 I
2/3 I
3/18 I
1/6 I3/18 I
1/6 I
I= Insulin Dosage*
I= 0,7U/Kg, Total 24h requirement for wk 6-18
I= 0,8U/Kg, Total 24h requirement for wk 6-18
I= 0,9U/Kg, Total 24h requirement for wk 6-18
I= 1,0U/Kg, Total 24h requirement for wk 6-18
* Sliding Scale For Irregular Insulin Dosage:
7:00 am blood glucose 4:30 pm blood glucose < 60 = 3/18 I
60-100 = 4/18 I
100-140 = 5/18 I
> 140 = 6/18 I< 60 = 2/18I
60-100 = 3/18 I
100-140 = 4/18 I
> 140 = 5/18 I
Adapted from Jovanovic L, Peterson CM: Optimal insulin delivery for
pregnant diabetic patient. Diabetes care 5 (suppl 1) : 24, 1982.
Insulin Tritation
Time Insulin is administered Insulin Type Time of blood glucose sample to monitor peak action Titration procedure 10:00 pm NPH 7:00 am If fasting glucose is > 100 mg/dL add 2 U to 10 pm NPH
If fasting glucose is < 60 mg/dL, decrease 10 pm NPH by 2 U7:30 am Regular 10:00 am If fasting postprandial glucose is > 140 mg/dL, add 2U of regular insulin to 7:30 am dose the following day 7:30 am NPH 4:00 pm If 4:00 pm glucose is 100 mg/dL, add 2U to 7:30 am NPH dose
If 4:00 pm glucose is < 60 mg/dL decrease 7:30 am NPH by 2U4:30 pm Regular 6:00 pm If 6:00 glucose is > 140 mg/dL, add 2U to regular insulin
From Jovanovic L, Peterson CM: Optimal insulin delivery for pregnant diabetic patient. Diabetes care 5 (suppl 1) : 24, 1982.
Exercise Therapy
Cardiovascular conditioning or aerobic exercise has both acute and long-term effects on insulin sensitivity, insulin secretion, and glucose metabolism. Because exercise is associated with a decrease in blood glucose concentration both acutely and after a training program and exercise training with weight control or reduction is associated with lower fasting and postprandial insulin concentrations and apparent increases in insulin sensitivity, regular exercise may be useful in the treatment or prevention of GDM.
There are many other potential benefits of exercise training and increased cardio-respiratory fitness, such as improvement in cardiovascular risk factors and the prevention or reduction of cardiovascular complications in people with diabetes.
Recognizing the importance of physical activity, the Third International Workshop-Conference on Gestational Diabetes has recommended exercise as a treatment modality for GDM in women who do not have a medical or obstetric contraindication for an exercise program.
Obstetric Management
Antepartum Care
Surveillance for fetal well-being should begin between 28 and 32 weeks. Methods of fetal surveillance may include fetal kick counts, the non-stress test (NST), the contraction stress test (CST), and the biophysical profile. Signs of fetal compromise include the following: decreased fetal movement, a non-reactive NST, a positive CST and a poor biophysical profile.
The frequency and timing of fetal surveillance depend on the severity of the disease and the degree of glycemic control. Frequent (every 4 to 6 weeks) ultrasound examinations to assess fetal growth should be performed.
In the case of abnormal fetal testing, the practitioner should assess gestational age and, if the fetus is found to be mature, should proceed to delivery. If the fetus is intermediate in maturity, amniotic fluid assessment for pulmonary maturity may assist in the decision regarding whether delivery should be effected. If the fetus is immature, further testing such as contraction stress tests or hospitalization with continuous fetal heart rate monitoring is advised.
Preterm labor is increased in patients with diabetes and they should be treated with magnesium sulfate as the initial tocolytic agent because the beta mimetics markedly influence glucose control. Corticosteroids increase maternal glucose levels, and this therapy may consist of continuous insulin infusion in certain cases.
Intrapartum and Postpartum Management
Induction of labor is recommended at 38 weeks in patients with poor glucose control and macrosomia. Insulin-requiring diabetics should be induced at 40 weeks' gestation if spontaneous labor has not occurred.
Induction of labor may be attempted if the fetus is not excessively large and if the cervix is capable of being induced (i.e., if the cervix is soft, appreciably effaced, and somewhat dilated).
The possibility of shoulder dystocia in the macrosomic infant of a mother with diabetes must be considered; cesarean section may be indicated to avoid the trauma of a delivering of a large infant (>4000g). Euglycemia should be maintained during labor.
Prognosis
Women diagnosed with gestational diabetes have an increased risk of developing diabetes mellitus in the future. If they require insulin for their pregnancy, there is a 50% risk of diabetes within 5 years. If dietary control has been sufficient, a 60% risk of developing diabetes mellitus within 10-15 years still persists.
For this reason, all gestationally diabetic patients should have a 75-g 3-hr glucose tolerance to evaluate for preexisting diabetes. If the 1-hr value is high, it represents decreased insulin capacity, whereas an elevated 3-hr value reflects decreased insulin receptors. In the former, limiting simple sugars in the diet should become a lifetime goal. In the latter, weight loss with increased abdominal musculature should significantly reduce the increased risk of diabetes.
Bibliography
1-American College of Obstetricians and Gynecologists: Management of diabetes mellitus in pregnancy. ACOG Tech Bull 92:1, 1986.
2-American Diabetes Association: Position Statement: Gestational diabetes. Diabetes Care 16 ( suppl 2 ):5, 1993.
3-Bevier WC,Jovanovic-Peterson L, Peterson CM: Pancreatic Disorders of Pregnancy: Diagnosis, Management and Outcome of Gestational Diabetes. Endocrinology and Metabolism Clinics of North America 24:1, 1995, pp103-138.
4-Carpenter MW, Coustan DR: Criteria for screening tests for gestational diabetes. Am.J Obstet Gynecol 144:768, 1982.
5-Combs CA, Gavin LA, Gunderson E, et al: Relationship of fetal macrosomia to maternal postprandial glucose control during pregnancy. Diabetes Care 15:1251, 1982.
6-Coustan DR, Nelson C, Carpenter MW, et al: Maternal age and screening for gestational diabetes: A population-based study. Obstet Gynecol 73:557,1989.
7-Jovanovic-Peterson L: Medical Management of Pregnancy Complicated by Diabetes by Diabetes. Alexandria, VA, American Diabetes Association, 1993, pp78-80.
8- Jovanovic-Peterson L, Peterson CM, Reed G et al: Postprandial blood glucose levels predict birth weight.: The Diabetes in Early Pregnancy Study.Am.J Obstet Gynecol 164:103,1991.
9- Metzger BE, Organizing committee: Summary and recommendations of the Third International WorkShop-Conference on Gestational Diabetes Mellitus. Diabetes 40 (suppl 2 ):197,1991.
10-Nanda K: Medical Complications of Pregnancy. Obstetrics and Gynecology, Beck,WW; 4th ed,1996.
11-Neiger R , Coustan DR: The role of repeat glucose tolerance tests in the diagnosis of gestational diabetes. Am J Obstet Gynecol 165:787,1991.
12-O'Sullivan JB, Mahan CM, Charles D, Dandrow RV: Screening criteria for high-risk gestational diabetic patients. Am J Obstet
drow RV: Screening criteria for high-risk gestational diabetic patients. Am J Obstet Gynecol 116:895,1973.
Information obtained from MedStudents.com: Obstetrics and Gynecology
MoonDragon's Pregnancy Information: Gestational Diabetes Index
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