Nashville Diabetes Dentist

Gestational diabetes (or gestational diabetes mellitus, GDM) is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy.

Gestational diabetes generally has few symptoms and it is most commonly diagnosed by screening during pregnancy. Diagnostic tests detect inappropriately high levels of glucose in blood samples. Gestational diabetes affects 3-10% of pregnancies, depending on the population studied.[1] No specific cause has been identified, but it is believed that the hormones produced during pregnancy increase a woman’s resistance to insulin, resulting in impaired glucose tolerance.

Babies born to mothers with gestational diabetes are at increased risk of problems typically such as being large for gestastional age (which may lead to delivery complications), low blood sugar, and jaundice. Gestational diabetes is a treatable condition and women who have adequate control of glucose levels can effectively decrease these risks.

Women with gestational diabetes are at increased risk of developing type 2 diabetes mellitus (or, very rarely, latent autoimmune diabetes or Type 1) after pregnancy, while their offspring are prone to developing childhood obesity, with type 2 diabetes later in life. Most patients are treated only with diet modification and moderate exercise but some take anti-diabetic drugs, including insulin.

Classification

Gestational diabetes is formally defined as “any degree of glucose intolerance with onset or first recognition during pregnancy”.This definition acknowledges the possibility that patients may have previously undiagnosed diabetes mellitus, or may have developed diabetes coincidentally with pregnancy. Whether symptoms subside after pregnancy is also irrelevant to the diagnosis.

The White classification, named after Priscilla White who pioneered in research on the effect of diabetes types on perinatal outcome, is widely used to assess maternal and fetal risk. It distinguishes between gestational diabetes (type A) and diabetes that existed prior to pregnancy (pregestational diabetes). These two groups are further subdivided according to their associated risks and management.

There are 2 subtypes of gestational diabetes (diabetes which began during pregnancy):

• Type A1: abnormal oral glucose tolerance test (OGTT) but normal blood glucose levels during fasting and 2 hours after meals; diet modification is sufficient to control glucose levels
• Type A2: abnormal OGTT compounded by abnormal glucose levels during fasting and/or after meals; additional therapy with insulin or other medications is required

The second group of diabetes which existed prior to pregnancy is also split up into several subtypes.

Causes

Classical risk factors for developing gestational diabetes are the following:

• a previous diagnosis of gestational diabetes or prediabetes, impaired glucose tolerance, or impaired fasting glycaemia
• a family history revealing a first degree relative with type 2 diabetes
• maternal age – a woman’s risk factor increases as she gets older (especially for women over 35 years of age)
• ethnic background (those with higher risk factors include African-Americans, Afro-Caribbeans, Native Americans, Hispanics, Pacific Islanders, and people originating from the Indian subcontinent)
• being overweight, obese or severely obese increases the risk by a factor 2.1, 3.6 and 8.6, respectively.
• a previous pregnancy which resulted in a child with a high birth weight (>90th centile, or >4000 g (8 lbs 12.8 oz))
• previous poor obstetric history

In addition to this, statistics show a double risk of GDM in smokers. Polycystic ovarian syndrome is also a risk factor, although relevant evidence remains controversial. Some studies have looked at more controversial potential risk factors, such as short stature.

About 40-60% of women with GDM have no demonstrable risk factor; for this reason many advocate to screen all women. Typically women with gestational diabetes exhibit no symptoms (another reason for universal screening), but some women may demonstrate increased thirst, increased urination, fatigue, nausea and vomiting, bladder infection, yeast infections and blurred vision.

Pathophysiology

Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1) on the cell membrane which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).

The precise mechanisms underlying gestational diabetes remain unknown. The hallmark of GDM is increased insulin resistance. Pregnancy hormones and other factors are thought to interfere with the action of insulin as it binds to the insulin receptor. The interference probably occurs at the level of the cell signaling pathway behind the insulin receptor.. Since insulin promotes the entry of glucose into most cells, insulin resistance prevents glucose from entering the cells properly. As a result, glucose remains in the bloodstream, where glucose levels rise. More insulin is needed to overcome this resistance; about 1.5-2.5 times more insulin is produced than in a normal pregnancy.

Insulin resistance is a normal phenomenon emerging in the second trimester of pregnancy, which progresses thereafter to levels seen in non-pregnant patients with type 2 diabetes. It is thought to secure glucose supply to the growing fetus. Women with GDM have an insulin resistance they cannot compensate with increased production in the β-cells of the pancreas. Placental hormones, and to a lesser extent increased fat deposits during pregnancy, seem to mediate insulin resistance during pregnancy. Cortisol and progesterone are the main culprits, but human placental lactogen, prolactin and estradiol contribute too.

It is unclear why some patients are unable to balance insulin needs and develop GDM, however a number of explanations have been given, similar to those in type 2 diabetes: autoimmunity, single gene mutations, obesity, and other mechanisms.

Because glucose travels across the placenta (through diffusion facilitated by GLUT3 carriers), the fetus is exposed to higher glucose levels. This leads to increased fetal levels of insulin (insulin itself cannot cross the placenta). The growth-stimulating effects of insulin can lead to excessive growth and a large body (macrosomia). After birth, the high glucose environment disappears, leaving these newborns with ongoing high insulin production and susceptibility to low blood glucose levels (hypoglycemia).

Screening

A number of screening and diagnostic tests have been used to look for high levels of glucose in plasma or serum in defined circumstances. One method is a stepwise approach where a suspicious result on a screening test is followed by diagnostic test. Alternatively, a more involved diagnostic test can be used directly at the first antenatal visit in high-risk patients (for example in those with polycystic ovarian syndrome or acanthosis nigricans).

Non-challenge blood glucose tests involve measuring glucose levels in blood samples without challenging the subject with glucose solutions. A blood glucose levels is determined when fasting, 2 hours after a meal, or simply at any random time. In contrast challenge tests involve drinking a glucose solution and measuring glucose concentration therafter in the blood; in diabetes they tend to remain high. The glucose solution have a very sweet taste that some women find unpleasant; sometimes therefore artificial flavours are added. Some women may experience nausea during the test, and more so with higher glucose levels.

Pathways

There are different opinions about optimal screening and diagnostic measures, in part due to differences in population risks, cost-effectiveness considerations, and lack of an evidence base to support large national screening programs. The most elaborate regime entails a random blood glucose test during a booking visit, a screening glucose challenge test around 24–28 weeks’ gestation, followed by an OGTT if the tests are outside normal limits. If there is a high suspicion, women may be tested earlier.

In the United States, most obstetricians prefer universal screening with a screening glucose tolerance test. In the United Kingdom, obstetric units often rely on risk factors and a random blood glucose test. The American Diabetes Association and the Society of Obstetricians and Gynaecologists of Canada recommend routine screening unless the patient is low risk (this means the woman must be younger than 25 years and have a body mass index less than 27, with no personal, ethnic or family risk factors) The Canadian Diabetes Association and the American College of Obstetricians and Gynecologists recommend universal screening. The U.S. Preventive Services Task Force found that there is insufficient evidence to recommend for or against routine screening.

Non-challenge blood glucose tests

When a plasma glucose level is found to be higher than 126 mg/dl (7.0 mmol/l) after fasting, or over 200 mg/dl (11.1 mmol/l) on any occasion, and if this is confirmed on a subsequent day, the diagnosis of GDM is made, and no further testing is required. These tests are typically performed at the first antenatal visit. They are patient-friendly and inexpensive, but have a lower test performance compared to the other tests, with moderate sensitivity, low specificity and high false positive rates.

Screening glucose challenge test

The screening glucose challenge test (sometimes called the O’Sullivan test) is performed between 24–28 weeks, and can be seen as a simplified version of the oral glucose tolerance test (OGTT). It involves drinking a solution containing 50 grams of glucose, and measuring blood levels 1 hour later.

If the cut-off point is set at 140 mg/dl (7.8 mmol/l), 80% of women with GDM will be detected. If this threshold for further testing is lowered to 130 mg/dl, 90% of GDM cases will be detected, but there will also be more women who will be subjected to a consequent OGTT unnecessarily.

Oral glucose tolerance test (OGTT)

The OGTT should be done in the morning after an overnight fast of between 8 and 14 hours. During the three previous days the subject must have an unrestricted diet (containing at least 150 g carbohydrate per day) and unlimited physical activity. The subject should remain seated during the test and should not smoke throughout the test.

The test involves drinking a solution containing a certain amount of glucose, and drawing blood to measure glucose levels at the start and on set time intervals thereafter.

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.

The following are the values which the American Diabetes Association considers to be abnormal during the 100 g of glucose OGTT:

• 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)

An alternative test uses a 75 g glucose load and measures the blood glucose levels before and after 1 and 2 hours, using the same reference values. This test will identify less women who are at risk, and there is only a weak concordance (agreement rate) between this test and a 3 hour 100 g test. There are some hospitals that do a 50 mg test, results will vary.

The glucose values used to detect gestational diabetes were first determined by O’Sullivan and Mahan (1964) in a retrospective cohort study (using a 100 grams of glucose OGTT) designed to detect risk of developing type 2 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 led to alterations in O’Sullivan’s criteria. When methods for blood glucose determination changed from the use of whole blood to venous plasma samples, the criteria for GDM were also changed.

Urinary glucose testing

Women with GDM may have high glucose levels in their urine (glucosuria). Although dipstick testing is widely practiced, it performs poorly, and discontinuing routine dipstick testing has not been shown to cause underdiagnosis where universal screening is performed. Increased glomerular filtration rates during pregnancy contribute to some 50% of women having glucose in their urine on dipstick tests at some point during their pregnancy. The sensitivity of glucosuria for GDM in the first 2 trimesters is only around 10% and the positive predictive value is around 20%.

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