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Gestational Diabetes

Thomas Higgins MD
10/25/98

Etiology: Pregnancy is a diabetogenic state manifested by increased insulin demands. This stems from the increased secretion of diabetogenic hormones during pregnancy including estrogen, prolactin, human chorionic somatomammotropin (human placental lactogen, hPL or hCS), cortisol, and progesterone. Appropriate metabolic adaptations occur in normal pregnant women which ensure that the fetus has an ample supply of fuel and nutrients at all times.

The fasted state in pregnancy is one of "accelerated starvation" in which alternative fuels are made available to the mother while glucose is reserved for the fetus. After an overnight fast, for example, the maternal venous plasma glucose drops to 63 to 75 mg/dL while plasma ketone and free fatty acid levels rise. The average plasma glucose concentration falls by about 20 percent during a normal pregnancy; a venous level of 95 mg/dL at any time except immediately post prandial is therefore elevated in pregnancy.

Gestational diabetes mellitus (GDM) occurs when a woman's pancreatic function is not sufficient to overcome the insulin resistance created by the anti-insulin hormones and the dietary intake necessary to provide for the growing mother and fetus. The diagnosis and management of GDM are important because of the association with increases in the incidence of fetal macrosomia with poor control and because of the associated increase in future development of overt diabetes mellitus in these patients. The late diabetes which develops in patients with a history of GDM is typically NIDDM. However, about 10 percent of patients with GDM have circulating islet cell antibodies and may have a "latent" form of type 1 diabetes. The risk of developing type 1 disease in these patients is not known.

An important point to be made is that "gestational diabetes" refers to diabetes which develops during pregnancy and that the diabetes was not present prior to pregnancy. This is in contrast to the woman who has either type 1 or type 2 diabetes prior to pregnancy. When diabetes is present prior to pregnancy, there can be an increase in the risk of development of congenital abnormalities in the fetus. When these abnormalities occur, they are related to poor diabetes control during the first 12 weeks of pregnancy when all of the major organ systems are developing in the fetus. The risk of these fetal abnormalities can be reduced by maintaining good diabetes control during early pregnancy. An increased risk of congenital abnormalities does not occur in women with gestational diabetes since the diabetes does not occur until later in pregnancy.

Prevalence And Epidemiology: The prevalence of GDM varies both worldwide and among racial and ethnic groups. Prevalence rates are higher in African Americans, Latino women, Native Americans and Asians. The prevalence also varies with the testing methods and diagnostic criteria. Thus, different studies have shown a relatively wide range in the prevalence rate of GDM in the United States from 1.4 to 12.3 percent. The overall national prevalence in the United States for pregnant women is 2.1 percent.

There are several clues that a pregnant woman may be high risk for GDM:

  • A family history of diabetes, especially in first degree relatives.
  • Pre-pregnancy obesity.
  • A previous large baby.
  • The mother was a large infant at birth (greater than 9 pounds).
  • A previous unexplained perinatal loss or birth of a malformed child.

These factors only identify approximately 50 percent of women diagnosed with GDM. As a result, screening for gestational diabetes is recommended in all pregnant women.

Screening And Diagnostic Criteria: Screening for GDM is optimally performed at 24 to 28 weeks of gestation. However, screening can be performed at any time if there is a high degree of suspicion that a first trimester pregnant woman has undiagnosed diabetes.

The algorithm for screening recommended by the American Diabetes Association can be summarized as follows:

  • Initially a 50 gram oral glucose challenge is given and a one hour plasma glucose level is obtained.
  • A value of 140 mg/dL is considered abnormal.

If the screen is abnormal, it is followed by a 100 gram, three hour oral glucose tolerance test.

The 100 gram OGTT as described by the criteria of O'Sullivan and Mahan in 1964 remains the diagnostic standard for GDM but the values have changed. According to the Fourth International Workshop (published in June, 1997), GDM is present if two or more of the following plasma glucose levels are exceeded:

  • Fasting plasma glucose concentration >95 mg/dL
  • One hour glucose concentration >180 mg/dL
  • Two hour glucose concentration >155 mg/dL
  • Three hour glucose concentration >140 mg/dL

The old values used for cutoffs were 105, 190, 165, and 145 mg/dL, respectively.

A diagnosis of GDM cannot be established without a confirmatory abnormal glucose tolerance test. I do not believe, however, that full GTT testing is always necessary and that treatment should be offered when other findings identify a women to be at risk. As an example, a plasma glucose that is >140 mg/dL after the 50 gram glucose challenge is associated with a 25 to 30 percent risk of a macrosomic infant if no treatment is offered. It has also been shown that a fasting plasma glucose concentration greater than 105 mg/dL at 24 to 28 weeks of gestation, along with a glycosylated hemoglobin level above normal, are highly sensitive and specific to predict subsequent macrosomic infants in the general obstetrical population.

Glycosylated hemoglobin by itself is not sufficiently sensitive to predict those women at risk of delivering a macrosomic infant.

Therapy: An effective treatment regimen consists of dietary management, self blood glucose monitoring, and the administration of insulin if the glucose targets are not met with diet alone.

Diet: Nutritional management is at the core of a good outcome for both the mother and child in GDM. An effective diet results in normoglycemia, prevention of ketosis, adequate weight gain, and good fetal health. A trial of dietary therapy should be instituted in any woman who meets the blood glucose criteria for GDM or who is at risk for developing GDM.

Glucose Monitoring: Women with GDM should monitor their blood glucose levels with the use of home blood glucose monitoring and fingerstick glucose should be measured at each visit. The degree of fasting glycemia in diagnosed GDM may not predict the need for insulin therapy. Thus, at least two glucose determinations should be twice weekly in women with diet-controlled GDM: fasting and 2 hours after breakfast. Two criteria should be met to assure that the degree of glycemic control is adequate to prevent macrosomia:

  • The fasting glucose level should be less than 105 mg/dL.
  • The glucose level 2 hours after breakfast should be less than 120 mg/dL.

Glycosylated Hemoglobin: Glycosylated hemoglobin levels are not sufficiently sensitive to aid in screening for gestational diabetes. They are, however, helpful in assessing glycemic control in a patient with GDM. The average plasma glucose is about 20 percent lower in pregnancy, leading to a similar reduction in the glycosylated hemoglobin ( and hemoglobin A1c) levels. Glycosylated hemoglobin levels should be measured every 3 months to provide the patient with positive feedback and to ascertain that self blood glucose monitoring accurately reflects maternal glycemic control.

Insulin Therapy: Approximately 15 percent of women with GDM require insulin therapy. Insulin should be initiated when the fasting glucose levels are greater than 105 mg/dL or the post prandial glucose level are greater than 120 mg/dL on two or more occasions within a two week interval despite attempted dietary control.

Glucose targets of preprandial levels below 90 mg/dL and 2 hour postprandial levels of 120 mg/dL have been shown to minimize the incidence of macrosomia.

The dose and type of insulin used to initiate therapy is dependent upon the specific abnormality of blood glucose noted during monitoring.

The insulin dose is then based upon the self blood glucose monitoring. It is important to appreciate that insulin resistance increases during the second and third trimesters, requiring an increase in insulin dose. A decrease in insulin requirements is often noted in the weeks just before delivery.

Exercise: Most GDM represents NIDDM that has been unmasked by pregnancy. One would therefore expect that treatment modalities such as exercise that diminish peripheral resistance to insulin would be beneficial in GDM. However, some concerns have been raised regarding the safety of exercise in pregnancy. Normal pregnancy is associated with a marked increase in cardiac output and blood volume. It is therefore possible that the additional stresses of exercise on a maternal cardiovascular system that is already approaching near maximum output could divert oxygen, fuel, and nutrients away from the fetus. Episodes of fetal bradycardia have been associated with maternal exercise.

Exercises using the upper body and avoiding mechanical stress on the trunk appear to be most appropriate, allowing the workload to be increased safely without distress to the fetus. In one study, for example, arm exercises against resistance were shown to be a safe and effective adjunct to diet in GDM. I recommend moderate walking with hand weights and arm exercises.

Peripartum Concerns: The great majority of women with GDM proceed to term and have a spontaneous vaginal delivery. Maternal hyperglycemia should be avoided during labor to prevent fetal hyperinsulinemia and subsequent neonatal hypoglycemia. The maternal plasma glucose concentration should be maintained between 70 and 90 mg/dL during labor. Insulin should not be required during labor in patients who were able to be controlled by diet alone. I find that an insulin drip during labor for the patient who requires insulin is very effective and that the insulin can be discontinued after delivery.

Postpartum Concerns And Future Risk: Nearly all women with GDM return to normoglycemia after delivery. However, they remain at risk for future GDM, impaired glucose tolerance, and the future development of overt diabetes.

  • One-third to two-thirds of patients will have GDM in a subsequent pregnancy. In one report, the women who had a recurrence tended to be older, more parous, and had an increase in weight between the pregnancies.
  • As many as 20 percent of women with GDM have impaired glucose tolerance in the early postpartum period. Gestational requirement for insulin, maternal obesity, elevated fasting glucose during pregnancy and early postpartum, and early gestational age at the time of diagnosis of GDM are risk factors for impaired glucose tolerance and overt diabetes at a later date.
  • A five year incidence of 47 to 50 percent for NIDDM has been found in two studies of women with GDM. The future risk of NIDDM is affected by body weight, representing a 50 to 75 percent risk in obese women versus less than 25 percent in women who achieve ideal body weight after delivery.

Recommendations: I recommend the following approach to immediate and prolonged follow-up:

  • Immediately after delivery, blood glucose should be monitored to ensure that the mother's levels have returned to normal. The fasting glucose levels should be below 115 mg/dL and the 2 hour postprandial value should be less than 140 mg/dL.
  • A woman with atypical GDM who may have been diagnosed with GDM early in gestation, is normal in weight, does not have a family history of NIDDM or required insulin during the pregnancy should be counseled to watched for the development of symptoms suggestive of Type 1 diabetes.
  • Obese women with a history of GDM should be counseled to lose weight and engage in moderate exercise.
  • All women with a history of GDM should be counseled regarding their risk for developing GDM in subsequent pregnancies and possible NIDDM (or IDDM) in the future. Weight loss and exercise are clearly beneficial and long-term follow-up is essential. A fasting and post prandial glucose should be done on a yearly basis. Values above 115 mg/dl fasting and 140 mg/dl non fasting are cause for concern and fasting values above 125 mg/dl on 2 occasions or above 200 mg/dl at any time are diagnostic of diabetes in non pregnant individuals.