Gestational diabetes overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]

Overview

Gestational diabetes (GDM) is a form of diabetes which affects pregnant women in second or third trimester 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.

Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs approximately 7.5 of all pregnancies in the United States and may improve or disappear after delivery. 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.

Historical Perspective

• Diabetes mellitus is an ancient term first found in Egyptian Eberes papyrus around 1500 BC. Hyperglycemia in pregnancy, first described by Bennewitz, a German physician in 1824. In 1950 GDM term was accepted.
• John B. O’Sullivan, Wilkerson and Remein in 1957 proposed offering a 3-hour oral glucose tolerance test (OGTT) for patients presenting risk factors for diabetes such as family history of diabetes, gestational glycosuria and overdeveloped infants at birth.

Classification

Gestational diabetes refers to hyperglycemia during second or third trimester of pregnancy. Diagnosis of diabetes in the second or third trimester of pregnancy that is not clearly either type 1 or type 2 diabetes.

Pathophysiology

Insulin insensitivity

Insulin sensitivity reduces slightly during first and second trimesters but it decreases 40-60% during third trimester. Other changes in molecular level that may lead to insulin resistant include: reduced ability of insulin to phosphorylate the insulin receptor, decreased expression of insulin receptor substrate 1 (IRS-1) and increased levels of a specific kinase.

Factors affecting insulin insensitivity include: estrogens and progesterone, human chorionic somatomammotropin (hCS) or placental lactogen (HPL), prolactin, placental growth hormone variant (hGH-V), corticotropin-releasing factor (CRF) and corticotropin, leptin, tumor necrosis factor α (TNF-α), adiponectin, resistin, ghrelin and interleukin-6.

Maternal metabolic changes

Basal and postprandial levels of glucose, FFAs, triglycerides, and amino acids are higher in GDM than of normal pregnancy.

Maternal hyperglycemia leads to fetal hyperinsulinism, which is responsible for macrosomia and neonatal morbidity. Development of macrosomia (defined as birth weight >4000 g or above the 90th percentile for gestational age) is a frequent complication of pregnancies complicated by DM and GDM.
Increased adiposity is the primary component of the macrosomia. Infants of diabetic mothers may have up to twice the body-fat content of infants of normal mothers.

Differentiating Gestational diabetes other Diseases

GDM must be differentiated from other causes of hyperglycemia during pregnancy for example diabetes type 1 or type 2.

Epidemiology and Demographics

Prevalence of gestational diabetes mellitus varies widely. It may range from 1% to 14% of all pregnancies.

The prevalence of GDM showed a 12% increase per year over the period from 1994 to 2002 in one study. It's increasing rate over time, possibly is due to increases in mean maternal age and weight.

In another study, Over the 7-year period, the age and race/ethnicity adjusted prevalence of GDM was from 7.5 per 100 in 1999 to 7.4 per 100 in 2005. In one study ethnical prevalence of GDM was higher in Asian/Pacific Islanders (relative risk=1.97), Hispanic (RR=1.69) and African-American(RR=1.26) than for caucasian women after adjustment for year and maternal age.

Risk Factors

Risk factors for gestational diabetes include:

• A family history of diabetes especially in first degree relatives
• Maternal age >25 yrs
• Certain ethnic groups (such as Native American, Hispanic-American, African-American, South or East Asian, Pacific Islander)
• Body mass index greater than 25 kg/m²
• Gestational diabetes or impaired glucose tolerance test in previous pregnancies
• Previous delivery of a baby >9 kg
• Personal history of impaired glucose tolerance or impared fasting glucose (pre-diabetes)
• Glycosuria at the first prenatal visit
• Certain medical conditions (such as metabolic syndrome, polycystic ovary syndrome (PCOS), current use of glucocorticoids, hypertension)
• Previous history of unexplained miscarriage or stillbirth
• Smoking doubles the risk of gestational diabetes
• Multiple gestation
• Genetic predisposition (.e.g. glucokinase mutation)

Screening

Screening can be performed during the first prenatal visit especially, if mother has risk factors for GDM. If the result is negative or test was not done during prenatal care, 24-28 weeks is the best time for screening mothers.

50 gram Glucose Test

• Regardless of fasting status of mother, 50 gram glucose is loaded and 1 hour later, plasma glucose level should be measured. Measures greater than 130 mg/dL are considered positive. Considering 130 mg/dl threshold has 88% to 99% sensitivity and 66% to 77% specificity.
• Next step is to confirm the diagnosis by performing a 100 gram 3 hour Glucose Test.

Natural History and Prognosis

• Most of women with GDM return to their pre pregnancy glycemic status after delivery.
• Women diagnosed with gestational diabetes have an increased risk of developing overt diabetes mellitus in the future. Women requiring insulin to manage gestational diabetes have a 50% risk of developing diabetes within the next five years.
• 1/3-2/3 women will re-experience GDM in subsequent pregnancies.
• Risk factors for recurrence include older age, multiparity, higher maternal weight in the index pregnancy and weight gain between pregnancies.

Complications

• Maternal complications of GDM can be categorized to obstetrical and long term glycemic status related complications.

Pre-eclampsia, polyhydramnios and difficult labor due to over weight baby are obstetrical complications. Risk of developing prediabetes or even overt diabetes is noticeable in GDM patients.

• Poor glycemic control and increased insulin level may result in increased metabolic demands in fetus which secondarily leads to fetal and neonatal complications. Large for gestational age, prematurity, respiratoray distress syndrome, hyperbilirubinemia, polycythemia and congenital anomalies are the most common complications for GDM mother's neonates.

Diagnosis

Diagnostic criteria

There are two method for diagnosis GDM.

One-step 75-g Oral glucose tolerance test and Two-step approach with a 50-g (nonfasting) screen followed by a 100-g OGTT for those who screen positive.

Both of them have good diagnostic yields and can improve diagnosis as early as possible.

History and Symptoms

• Usually there are no symptoms, or the symptoms are mild and not life threatening to the pregnant woman.

• Symptoms may include:

• Blurred vision
• Fatigue
• Frequent infections, including those of the bladder, vagina, and skin
• Increased thirst
• Increased urination
• Nausea and vomiting
• Weight loss in spite of increased appetite
• Excessive thirst

Physical Examination

There is no specific physical examination finding for gestational diabetes. Signs of insulin resistance (i.e. acanthosis nigricans) may be seen in physical examination.

Laboratory Findings

Generally a test for gestational diabetes is carried out between the 24th and 28th week of pregnancy.

If patient is at risk for gestational diabetes (see risk factors) he or she could prescribe a glucose test earlier in the pregnancy.

Treatment

After diagnosis, treatment starts with medical nutrition therapy, physical activity, and weight management depending on pregestational weight.
Target glucose control in gestational diabetes are:

• Fasting <95 mg/dL (5.3 mmol/L)

• One-hour postprandial <140 mg/dL (7.8 mmol/L)

• Two-hour postprandial <120 mg/dL (6.7 mmol/L)

Dietary Therapy

• Many randomized controlled trials suggest that the risk of GDM may be reduced by diet, exercise, and lifestyle counseling.
• 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.

Insulin Therapy

All insulins are pregnancy category B except for glargine, glulisine and degludec which are labeled category C. Insulin therapy in patients with GDM is based on pre-pregnancy BMI.

• In the first trimester, the insulin requirement is approximately 0.7 units per kilogram times the pregnant weight of the woman.
• By the second trimester, the insulin requirement is 0.8 units per kilogram.
• By term, the insulin requirement is 0.9 times 1.0 unit per kilogram pregnant weight per day.

Oral Hypoglycemics

Sulfonylureas

Recent studies showed that sulfonylureas, such as glyburide, may be inferior to insulin and metformin due to increased risk of neonatal hypoglycemia and macrosomia with this class.

Metformin

It is associated with a lower risk of hypoglycemia and potential lower weight gain, may be preferable to insulin for maternal health if it suffices to control hyperglycemia however, metformin may slightly increase the risk of prematurity.

Primary Prevention

Weight control, dietary control and life style modification are the main stay of preventing GDM.

Secondary Prevention

After delivery, mothers who diagnosed with GDM, should have close follow up to prevent overt diabetes in future. Testing with 75 g OGTT 6 to 12 weeks after delivery and then every 1-3 years is recommended for early diagnosis.