Gestational diabetes

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 * Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [mailto:psingh@perfuse.org];

Overview
Gestational diabetes (GDM) is a form of diabetes which affects pregnant women who have never had diabetes before. There is no known specific cause, but it's believed that the hormones produced during pregnancy reduce a woman's receptivity to insulin resulting in high blood sugar.

Diabetes mellitus and pregnancy

Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2%–5% of all pregnancies and may improve or disappear after delivery. Gestational diabetes is fully treatable but requires careful medical supervision throughout the pregnancy. About 20%–50% of affected women develop type 2 diabetes later in life.

Even though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital cardiac and central nervous system anomalies, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant production and cause respiratory distress syndrome. Hyperbilirubinemia may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental profusion due to vascular impairment. Induction may be indicated with decreased placental function. A cesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.

Types
There are 2 types of gestational diabetes (diabetes which began during pregnancy): Additionally, it is useful to classify different forms of diabetes during pregnancy which existed prior to pregnancy:
 * Type A1: diet modification is sufficient to control glucose levels
 * Type A2: insulin or other medications are required
 * Type B: onset at age 20 or older or with duration of less than 10 years
 * Type C: onset at age 10-19 or duration of 1-19 years
 * Type D: onset before age 10 or duration greater than 20 years
 * Type F: diabetic nephropathy
 * Type R: diabetic retinopathy
 * Type H: diabetes with ischemic heart disease
 * Type T: diabetes requiring kidney transplant

Pathophysiology
Pregnancy is a state of relative insulin insensitivity. During the early part of pregnancy there is increase in insulin secretion and beta cell hyperplasia. This leads to an increase in insulin sensitivity with low fasting blood sugar levels, increased glucose uptake by peripheral tissue and glycogen storage as well as decreased hepatic gluconeogenesis. This process is crucial for the build-up of maternal adipose tissue, to be used in the later part of pregnancy. During the late phase, there is an increase in hormones such as cortisol, prolactin, progesterone and human placental lactogen which leads to a state of relative insulin resistance, possibly via a post receptor defect in the cells. This is a critical step which ensures adequate delivery of nutrients to the fetus. The pancreas respond to this increased resistance by doubling the release of insulin.

It has been found that women diagnosed with gestational diabetes already have insulin resistance at baseline with a higher level of plasma insulin levels. This state gets further aggravated by the metabolic changes associated with pregnancy. The pancreas however, is unable to cope with this additional stress of elevated level of insulin resistance. This results in an inadequate release of insulin and elevated blood sugar levels.

Risk factors
Risk factors for gestational diabetes include:
 * a family history of type 2 diabetes
 * maternal age - a woman's risk factor increases the older she is
 * ethnic background (those with higher risk factors include African-Americans, North American native peoples and Hispanics)
 * obesity
 * gestational diabetes in a previous pregnancy
 * a previous pregnancy which resulted in a child with a birth weight of 9 pounds or more
 * if you have been diagnosed with prediabetes, impaired glucose tolerance, or impared fasting glucose
 * smoking doubles the risk of gestational diabetes

Presentation
Frequently women with gestational diabetes exhibit no symptoms. However, possible symptoms include increased thirst, increased urination, fatigue, nausea and vomiting, bladder and yeast infection, and blurred vision.

Testing and treatment
Generally a test for gestational diabetes is carried out between the 24th and 28th week of pregnancy. If your doctor believes you could be at risk for gestational diabetes (see Risk Factors) he or she could prescribe a glucose test earlier in the pregnancy.

Often, gestational diabetes can be managed through a combination of diet and exercise. If that is not possible, it is treated with insulin(usually 15% need Insulin), in a similar manner to diabetes mellitus.

Diagnosis
A health care team will check the affected person's blood glucose level. Depending on the mother's risk and her test results, she may have one or more of the following tests.


 * Fasting blood glucose or random blood glucose test
 * Screening glucose challenge test
 * Oral glucose tolerance test (OGTT)

Screening glucose challenge test
There are several tests intended to identify gestational diabetes in pregnant women. The first, called the Screening glucose challenge test, is a preliminary screening test performed between 26-28 weeks. If a woman tests positive during this screening test, the second test, called the Glucose Tolerance Test, may be performed. This test will diagnose whether diabetes exists or not by indicating whether or not the body is using glucose (a type of sugar) effectively. The Glucose Challenge Screening is now considered to be a standard test performed during the second trimester of pregnancy.

The glucose values used to detect gestational diabetes were first determined by O'Sullivan and Mahan (1964) in a retrospective study designed to detect risk of developing type II diabetes in the future. The values were set using whole blood and required two 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).

The diagnostic criteria from the National Diabetes Data Group (NDDG) have been used most often, but some centers rely on the Carpenter and Coustan criteria, which set the cutoff for normal at lower values. Compared with the NDDG criteria, the Carpenter and Coustan criteria lead to a diagnosis of gestational diabetes in 54 percent more pregnant women, with an increased cost and no compelling evidence of improved perinatal outcomes.

Oral glucose tolerance test
Women who are considered at risk for gestational diabetes are given a screening test called a 50 gram glucose challenge between the 24th and 28th weeks of pregnancy (those with two or more risk factors may be tested earlier). The glucose challenge is performed by giving 50 grams of a glucose drink and then drawing a blood sample one hour later and measuring the level of blood glucose present. Women with a blood sugar level greater than 140 mg/dl may have gestational diabetes, and require a follow up test called a 3-hour oral glucose tolerance test (OGTT).

The test should be done in the morning after an overnight fast of between 8 and 14 h and after at least 3 days of unrestricted diet (>=150 g carbohydrate per day) and unlimited physical activity. The subject should remain seated and should not smoke throughout the test. The American Diabetes Association sets the following guidelines for results from the OGTT (oral glucose tolerance test)



Fasting blood glucose or random blood glucose test
A fasting plasma glucose level >126 mg/dl (7.0 mmol/l) or a casual plasma glucose >200 mg/dl (11.1 mmol/l) meets the threshold for the diagnosis of diabetes, if confirmed on a subsequent day, and precludes the need for any glucose challenge. In the absence of this degree of hyperglycemia, evaluation for GDM in women with average or high-risk characteristics should follow one of two approaches:


 * One-step approach
 * Two-step approach

The following are the values which the American Diabetes Association considers to be abnormal during the Glucose Tolerance Test:


 * Fasting Blood Glucose Level≥95 mg/dl (5.33 mmol/L)
 * 1 Hour Blood Glucose Level≥180 mg/dl (10 mmol/L)
 * 2 Hour Blood Glucose Level≥155 mg/dl (8.6 mmol/L)
 * 3 Hour Blood Glucose Level≥140 mg/dl (7.8 mmol/L)

Associated conditions
Poorly controlled gestational diabetes can lead to the growth of a macrosomic or large baby. This in turn increases the risk of instrumental deliveries (eg forceps, vacuum and caesarean section). Babies born to mothers with diabetes are also more likely to have hypoglycemia and other chemical imbalances which need to be monitored and possibly corrected after birth. These babies may need specialized care in the post partum period. Additionally, poor control of diabetes can lead to a variety of birth defects involving the heart, kidneys, eyes, and central nervous system, as well as increased risk of miscarriage. However birth defects are more common in babies whose mother had diabetes in the first trimester, in which case the mother likely had undiagnosed Type 1 or Type 2 diabetes, rather than gestational diabetes. Gestational diabetes typically does not occur until after the period of organogenesis, thus birth defects are unlikely.

In the future the mother is at increased risk of developing type 2 diabetes.

Treatment
Specific treatment will be determined by the physician(s) based on:


 * age, overall health, and medical history
 * extent of the disease
 * tolerance for specific medications, procedures, or therapies
 * expectations for the course of the disease
 * opinion or preference

Treatment for gestational diabetes focuses on keeping blood glucose levels in the normal range. Treatment may include:


 * special diet
 * exercise
 * daily blood glucose monitoring
 * insulin injections
 * there is evidence that certain oral glycemic agents such as glyburide are safe in pregnancy, or at least, are significantly less dangerous to the developing fetus than poorly controlled diabetes. However, few studies have been performed as of this time.

Diet and Exercise
All women diagnosed with GDM require nutritional counseling for the appropriate amount of weight gain during pregnancy as well as dietary control. Women with a normal BMI [20-25], can consume about 30kcal/kg/d while those who are obese [BMI >25-34] should restrict their diet to 25 kcal/kg/d and those that have a BMI >34 should consume 20kcal/kg/d or less. These patients should restrict fat intake and substitute simple or refined sugars in their diet to more complex carbohydrates. Moderate amount of non-weight bearing exercise is an important adjunct to dietary advice. It is recommended that pregnant women exercise for about 20-30 minutes everyday or at least most days of the week. It is a critical point in time for changing the lifestyles of these women since they are at a high risk for development of type 2 diabetes.

Insulin therapy
Insulin therapy in patients with GDM is based on pre-pregnancy BMI. Women who are lean before conception, the insulin dose requirement is 0.8U/Kg and for the obese women it is 0.9-1U/kg. There is insufficient evidence available regarding the safety of the insulin analogues, Aspart and Lispro hence regular human insulin is the treatment of choice and can be combined with intermediate or basal insulin such as NPH/ lente/ ultralente. There isn’t enough data regarding the safety of the long acting insulin glargine in pregnancy.

Oral Hypoglycemics
The use of oral medications is considered when diet and exercise do not adequately control blood sugars. Some studies have recently evaluated the safety and efficacy of Glyburide          [sulphonylurea] after the first trimester for treatment of GDM. The older sulphonylureas were not recommended for use in pregnancy because they crossed the placenta. Glyburide only minimally crosses the placenta. It has been shown that it is as effective as insulin, more cost effective than insulin and safe for use in pregnancy. Both American Diabetic Association [ADA] and American college of Obstetricians and Gynecologists [ACOG] await more research related to the effect of glyburide on maternal and perinatal outcomes before approving its use. There is inadequate data in regards to the safety and efficacy of other oral antidiabetic medications such as Metformin, thiazolidinediones and Acarbose.

Complications
Unlike pre-gestational diabetes, gestational diabetes generally does not cause birth defects. Birth defects usually originate sometime during the first trimester (before the 13th week) of pregnancy.

Infants of mothers with gestational diabetes are vulnerable to several chemical imbalances, such as low serum calcium and low serum magnesium levels, but in general, there are two major problems of gestational diabetes: macrosomia and hypoglycemia.

For Mother
 * Hypertension
 * Preeclampsia
 * Increased risk for developing type 2 diabetes

For Baby
 * Macrosomia (macrosomia can also increase the likelihood of a caesarean-section delivery)
 * Hypoglycemia
 * Jaundice
 * Low calcium and magnesium
 * Respiratory distress syndrome (RDS)
 * Increased risk for childhood and adult obesity
 * Increased risk of type 2 diabetes later in life

Postnatal Care
Approximately 50% women will develop type 2 diabetes within 5 years of development of gestational diabetes. The greatest risk factor for early-onset type 2 diabetes after pregnancy was early gestational age at the time of diagnosis and elevated fasting glucose. The greatest long term risk factor was maternal obesity. Hence these women should be screened by a 75 gm 2 hour oral glucose tolerance test. The children of women diagnosed with GDM are at increased risk of obesity and abnormal glucose metabolism during childhood, adolescence and adulthood. One of the mechanisms thought to be contributing to the long term complications in these babies is ‘early onset hyperinsulinimia’. Hence these children need close follow up.

Prognosis
Gestational diabetes generally resolves once the baby is born. However, women diagnosed with gestational diabetes have an increased risk of developing diabetes mellitus in the future. Women requiring insulin to manage gestational diabetes have a 50% risk of developing diabetes within the next five years.