Gestational Diabetes Mellitus: Risks, Complications, and Therapeutic Outcomes

Glucose is the principal nutrient that a mother supplies to her fetus through the placenta. This occurs by way of concentration-dependent mechanisms. What are the implications when those mechanisms go awry? Any degree of glucose intolerance with onset or first recognition during pregnancy is considered gestational diabetes mellitus (GDM). Whether diet alone or insulin is used for treatment and whether or not the condition persists after pregnancy, the definition still applies.

Prevalence

Approximately 135,000 cases of gestational diabetes mellitus are diagnosed annually, arising from ~4% of all pregnancies. The rate may be much higher in certain populations (e.g., Asians, Native Americans, Mexican-Americans, Pacific Islanders, Indians). Depending on the diagnostic tests and the population studied, prevalence may range from 1%–14% of all pregnancies.

Risks to Patient and Offspring

Women with GDM are at increased risk of developing diabetes, usually type 2, after pregnancy. An increased risk of type 1 diabetes is associated with markers of islet cell-directed autoimmunity. Factors, including obesity, that promote insulin resistance appear to contribute to the risk of type 2 diabetes. Because the prevalence of obesity is currently rising in developed countries (making pregravid overweight one of the most common high-risk obstetric situations), it is not surprising that even moderate overweight is a risk factor for gestational diabetes mellitus and hypertensive disorders of pregnancy. A recent study sought to determine the association between pregnancy-induced hypertension (PIH) and carbohydrate intolerance in pregnancy. After adjusting for maternal age, body mass index (BMI), parity, and ethnic origin, results showed a significant residual risk of PIH among individuals with gestational diabetes mellitus. The effects of GDM also may affect the patient’s offspring, resulting in an increased risk of obesity, glucose intolerance, and diabetes in late adolescence and young adulthood. Another recent study compared the pregnancy complications, obstetric outcomes, and perinatal outcomes between women with early-onset and late-onset gestational diabetes mellitus. Researchers concluded that women with an early diagnosis of gestational diabetes mellitus represent a high-risk subgroup. The likelihood of hypertension, higher glycemic values and the need for insulin, neonatal hypoglycemia, and perinatal deaths were greater in the women diagnosed with GDM during early pregnancy. Smoking in pregnancy also has been shown to direct parameters of glucose homeostasis toward gestational diabetes mellitus. During the last 4–8 weeks of gestation, an increased risk of fetal death may be associated with fasting hyperglycemia(>105 mg/dL). An increased frequency of the need for cesarean delivery has been documented and may result from changes in obstetric management and/or fetal growth disorders.

Risk Assessment

At the first prenatal visit, patients should undergo a risk assessment. Glucose testing should be done on those women with a high risk of gestational diabetes mellitus (a family history of diabetes, marked obesity, glycosuria, and personal history of GDM). Even if initial testing is negative for gestational diabetes mellitus, high-risk individuals should be retested between 24 and 28 weeks of gestation, the timeframe at which women of average risk are initially tested. A low-risk patient requires no glucose testing; however, she must meet all low-risk characteristics (TABLE 1) outlined in the Clinical Practice Recommendations 2000 of the American Diabetes Association (ADA). Due to infant macrosomia and a lifelong risk of developing diabetes associated with uncontrolled GDM, some researchers and clinicians recommend that all pregnant women be screened for carbohydrate intolerance.

Testing

When a fasting plasma glucose level >126 mg/dL or a casual plasma glucose level >200 mg/dL is confirmed on a subsequent day, the need for glucose challenge is unnecessary because these values meet the threshold for the diagnosis of diabetes. If this is not the case, one of two approaches should be followed to evaluate for gestational diabetes mellitus in women with average- or high-risk characteristics. The one-step approach may be cost-effective in high-risk patients/populations and consists of an oral glucose tolerance test (OGTT) without prior plasma or serum glucose screening. The two-step approach first measures the plasma or serum glucose concentration 1 h after a 50-g oral glucose load (glucose challenge test [GCT]). Then, on that subset of women exceeding the glucose threshold on the GCT, a diagnostic OGTT is performed. If a glucose threshold cutoff of >140 mg/dL is employed, approximately 80% of women with GDM may be identified. The yield increases to 90% by using a cutoff of >130 mg/dL. The diagnosis of GDM is based on an OGTT with either approach (a 100-g OGTT being better validated than a 75-g OGTT). A preparatory diet, thought to reduce false-positive diagnosis of GDM, does not significantly alter results of an OGTT and unnecessarily delays the diagnosis of gestational diabetes mellitus.

Monitoring

It appears that daily self-monitoring of blood glucose (SMBG) is superior to plasma glucose monitoring at periodic office visits. For those on insulin therapy, postprandial monitoring is superior to preprandial monitoring. Urine ketone monitoring may be helpful in determining sufficient caloric or carbohydrate intake, but urine glucose monitoring is not useful in gestational diabetes mellitus. Blood pressure and urine protein monitoring are useful in detecting hypertensive disorders. Techniques used to assess fetal demise depend on cumulative risk from GDM and other conditions, but are particularly appropriate when fasting glucose levels exceed 105 mg/dL or the pregnancy continues past term.

Management

When possible, individualized medical nutrition therapy (MNT) by a registered dietitian is recommended to all women with gestational diabetes mellitus. Balancing adequate calories and nutrients with maternal blood glucose goals is the key. For obese women (BMI >30), an intake of ~1,800 kcal/day can reduce hyperglycemia and plasma triglycerides with no increase in ketonuria. Concentrated sweets and excessive prenatal weight gain (>9 kg) should be avoided. Oral glucose-lowering agents are not recommended during pregnancy. The only pharmacological therapy known to reduce fetal morbidities when added to MNT is insulin. Human insulin is recommended to minimize antibody formation. At this time, the use of insulin analogs in GDM has not been adequately tested. Candidates for insulin therapy are identified based on maternal glucose levels (with or without an assessment of fetal growth characteristics) when MNT alone cannot maintain fasting whole blood glucose levels < or = 95 mg/dL or 2-h postprandial levels < or =120 mg/dL. A HbA1c concentration of <8% reflects good control in pregnancy. Exercise is beneficial and has been shown to lower maternal glucose concentrations. Gestation >42 weeks should be avoided, and ADA guidelines recommend delivery during the 38th week to decrease risk of fetal macrosomia. All patients and their families should be instructed in the subcutaneous administration of glucagon in case of severe hypoglycemia (plasma glucose <40 mg/dL, confusion, unconsciousness).

Postpartum Issues

Breast-feeding should be encouraged in women with GDM but may be associated with hypoglycemia in women with type 1. Patients with type 2 diabetes should be maintained on insulin (vs. oral hypoglycemics) while breast-feeding.

Uncontrolled gestational diabetes mellitus is associated with infant macrosomia and a lifelong risk of developing diabetes for both mother and offspring.

Conclusion

Gestational diabetes mellitus, when uncontrolled, is associated with infant macrosomia and a lifelong risk of developing diabetes for both mother and offspring. Obese women should be referred to a dietitian as part of preconception counseling (when possible) and followed dietetically and medically during gestation. The maintenance of normal body weight through MNT and exercise, avoidance of medications that increase insulin resistance (glucocorticoids, nicotinic acid), and reassessment of glycemia are important for long-term management. Offspring of women with gestational diabetes mellitus should be followed closely for the development of obesity and/or abnormalities of glucose tolerance. To reduce the risk of negative outcomes for patient and offspring, prompt diagnosis and aggressive management of GDM is critical. The pharmacist’s knowledge, monitoring capabilities, and counseling skills may be integrated at every stage of this illness to produce beneficial outcomes.