ABSTRACT: Gestational diabetes occurs as a result of insulin resistance during pregnancy. Adequate blood glucose control is important in helping prevent complications in the mother, such as preeclampsia, and in the fetus, such as macrosomia and stillbirth. Nonpharmacologic measures, including diet and exercise, are often sufficient for many women to maintain appropriate glycemic control. However, some women may require additional pharmacologic therapy including insulin, metformin, or glyburide. Additionally, women with gestational diabetes should be screened postpartum because they are at increased risk for developing overt diabetes after pregnancy.
US Pharm. 2017:42(10):47-50.
Gestational diabetes mellitus is defined as diabetes that is first diagnosed in the second or third trimester of pregnancy and is not considered overt type 1 or type 2 diabetes.1 For this reason, it is important that all pregnant women who have risk factors for diabetes be tested in the first trimester to rule out the presence of overt or preexisting diabetes.1
The exact prevalence of gestational diabetes depends on the population and the criteria used for diagnosis, but roughly 4% to 6% of all pregnancies are impacted by gestational diabetes.2,3 In recent years, there has been an increasing incidence of gestational diabetes that mirrors the trend of increasing obesity in the United States.4
It is proposed that gestational diabetes is related to a change in the way a woman’s body responds to insulin in pregnancy. Insulin is the hormone that allows glucose to move from the bloodstream to the body’s cells so that the glucose can be used for energy. In order to increase nutrients—including glucose—available to the fetus during pregnancy, the body naturally becomes more resistant to insulin. The body compensates for the resistance by increasing insulin levels; however, in some women, this is insufficient to maintain blood sugar control.5
Uncontrolled blood sugar can potentially impact the mother and/or fetus. Gestational diabetes can increase the risk of complications such as stillbirth, preeclampsia (onset of high blood pressure and proteinuria after 20 weeks’ gestation), and macrosomia (delivery of a larger-than-average baby). These complications may increase the rate of cesarean section in women with gestational diabetes; the procedure is performed to avoid birthing complications such as shoulder dystocia/birth trauma.3 The newborn infant may also be at risk for hypoglycemia or hyperbilirubinemia.2,3 The risk of complications may be decreased with proper control of blood sugar.
In addition to the health impact, gestational diabetes also has an economic impact, resulting in longer hospital stays and higher hospital costs.6 While most cases of gestational diabetes resolve after delivery, women with gestational diabetes are estimated to have a sevenfold increased risk of developing overt diabetes at some point postpregnancy, compared with women without gestational diabetes.7 Therefore, these women should be screened initially for overt diabetes 4 to 12 weeks after giving birth and at least every 3 years thereafter.1,7
Risk factors for the development of gestational diabetes include gestational diabetes in a previous pregnancy, body-mass index greater than or equal to 25.0 kg/m2, family history of diabetes, age greater than 35 years (or in some cases >25 years), ethnicity (Asian, Native American, Pacific Islander, black, Hispanic), giving birth to a large baby previously (>8.8 lb), and stillbirth in a previous pregnancy.2,3,5,8
SCREENING AND DIAGNOSIS
The American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) recommend that all pregnant women without overt type 1 or type 2 diabetes be screened for gestational diabetes between 24 and 28 weeks gestation.1,7 This can be accomplished in two different ways, through either a one-step or two-step process.
The one-step process involves a 75-g oral glucose tolerance test (OGTT), which requires that the patient fast for at least 8 hours overnight prior to administration of the glucose drink. Blood glucose concentrations are checked at 0, 1, and 2 hours. A diagnosis of gestational diabetes is confirmed when at least one of the values meets or exceeds the accepted threshold (fasting: 92 mg/dL; 1 hour: 180 mg/dL; 2 hours: 153 mg/dL).1,7
The two-step process involves an initial non-fasting 50-g oral glucose challenge test/glucose load test, in which a blood glucose concentration is drawn after 1 hour. If a patient’s blood glucose concentration meets or exceeds the accepted threshold, testing moves to the second step. The accepted blood glucose threshold varies depending on the provider, but the generally accepted thresholds are 130 mg/dL, 135 mg/dL, or 140 mg/dL. The second step involves a 100-g OGTT, which also requires that the patient fast for at least 8 hours overnight prior to administration of the glucose drink. Blood glucose concentrations are checked at 0, 1, 2, and 3 hours. A diagnosis of gestational diabetes is confirmed when at least two of the values meet or exceed the accepted threshold. There are two sets of accepted thresholds, the Carpenter-Coustan criteria and the National Diabetes Data Group criteria, as outlined in Table 1.1,7,9
TREATMENT
The overall goal of identifying and managing gestational diabetes is to prevent maternal and fetal complications. Multiple studies have demonstrated that proper management results in a reduction in complications such as preeclampsia and macrosomia.7 Proper management of gestational diabetes may involve nonpharmacologic measures with or without the addition of pharmacologic options as appropriate.
Nonpharmacologic Management
Approximately three-quarters of women diagnosed with gestational diabetes are able to manage their blood sugar with lifestyle modifications alone.1 Lifestyle modifications may include dietary measures and regular physical activity. It is recommended that a woman with gestational diabetes receive individualized nutritional counseling from a registered dietician when possible. This can help ensure that she achieves blood glucose goals, gains weight appropriately, and prevents ketosis.7 As a general guideline, the ACOG emphasizes carbohydrate intake as the main focal point for nutritional interventions. Carbohydrates should be limited to 33% to 40% of calories, with the remaining calories distributed between fat (~40%) and protein (~20%). Complex carbohydrates are preferred over simple carbohydrates to limit the impact on postprandial blood glucose concentrations.7 Although data from trials specific to gestational diabetes are limited, 30 minutes of moderate physical activity most days of the week is generally recommended; this is similar to the recommendation for patients with overt diabetes.3
Pharmacologic Treatment
Some women who have gestational diabetes may require pharmacologic interventions in addition to lifestyle modifications to achieve adequate glycemic control. Pharmacologic options for gestational diabetes are similar to those used for pregnant patients with overt diabetes and include insulin, metformin, or sulfonylureas.
As in overt diabetes, there are established blood glucose concentration goals for the proper management of gestational diabetes. The ACOG and the ADA are similar in their monitoring recommendations for either a 1-hour postprandial blood glucose ≤140 mg/dL or a 2-hour postprandial blood glucose ≤120 mg/dL.1,7 The ACOG states that evidence is more limited regarding the impact of fasting blood glucose concentrations, and it does not make a formal recommendation.7 While it is no longer emphasized, the ADA sets a fasting blood glucose goal of ≤95 mg/dL.1
Insulin: Insulin is considered the first-line option for women requiring pharmacologic intervention for gestational diabetes. It is emphasized in the ADA 2017 Standards of Care as the preferred option because it does not cross the placenta and is therefore associated with potentially fewer adverse effects than the other options.1 Depending on which glucose readings are elevated, basal and/or prandial (mealtime) insulin may be appropriate. The usual starting dose for insulin is 0.7 to 1.0 Units/kg/day given in divided doses.3,7 Rapid-acting insulins, such as aspart and lispro, may be more helpful at meals than short-acting regular insulin in reducing postprandial glucose concentrations.7 Adverse effects of insulin in patients with gestational diabetes are similar to those in patients with overt diabetes and may include hypoglycemia and weight gain.10 Recommended monitoring for patients on insulin includes frequent self-monitoring of blood glucose (SMBG) before and after meals (up to 8 times per day), as well as monitoring A1C throughout pregnancy.11 Patients should be made aware of signs of low blood sugar, such as dizziness and lightheadedness, and counseled on how to properly address them.
Metformin: Although it is not FDA approved for gestational-diabetes treatment, metformin is an alternative option to help control blood glucose.3,7 Unlike insulin, metformin does cross the placenta; however, available data suggest it carries a low risk in pregnancy.12 Metformin is associated with less weight gain than insulin, which may be beneficial in some pregnant women. Depending on the degree of blood glucose elevations, metformin alone may not be sufficient to achieve adequate glycemic control and may ultimately require the addition of insulin therapy.1 Metformin is typically started at 500 mg daily with food and titrated slowly, to limit gastrointestinal side effects, to a maximum of 2,500 mg daily in divided doses.3,12 Patients should have their renal function (estimated glomerular filtration rate) checked prior to initiating metformin. The main monitoring parameter for patients on metformin is SMBG, but A1C may also be checked.
Sulfonylureas: Glyburide, also not FDA-approved for the treatment of gestational diabetes, may be used to help manage blood glucose.3,7 The concern with glyburide is that it crosses the placenta and may cause greater hypoglycemia and macrosomia in neonates compared with insulin and metformin.1,13 Generally, dosing for gestational diabetes is comparable to dosing for overt diabetes, but some pregnant women require higher doses—up to 30 mg per day. As with metformin, some patients started on glyburide require the addition of insulin to adequately control blood glucose concentrations.7 Renal function should be checked prior to initiating glyburide. As with insulin, patients should be made aware of the risk of hypoglycemia as well as ways to address it.
PHARMACIST’S ROLE
Pharmacists can serve patients with gestational diabetes in a variety of ways. Since self-care is a vital component of gestational-diabetes management, pharmacists can play a significant role by providing patients with education related to gestational diabetes. Patients should be counseled on appropriate SMBG, including teaching proper finger-stick technique and explaining blood sugar goals. Pharmacists can also provide nutritional and exercise counseling to help manage blood sugar. If patients require pharmacologic treatment, pharmacists can counsel them on appropriate administration of medications used in gestational diabetes.
CONCLUSION
Gestational diabetes is a condition that can impact both the mother and the fetus, which is why adequate glycemic control is important in helping prevent complications. Nonpharmacologic measures such as diet and exercise are often sufficient for many women to maintain appropriate blood glucose concentrations. However, some women may require additional pharmacologic therapy, in which case insulin is typically the first-line choice, followed by metformin or glyburide. To ensure that patients with gestational diabetes are achieving adequate glycemic control, self-monitoring of blood glucose concentrations 1 or 2 hours postprandially is most often recommended. Additionally, these women should be screened postpartum, as they are at increased risk for developing overt diabetes.
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5. American College of Obstetricians and Gynecologists. Frequently asked questions: gestational diabetes. September 2013. www.acog.org/Patients/FAQs/Gestational-Diabetes\. Accessed May 25, 2017.
6. Wier LM, Whitt E, Burgess J, Elixhauser A. Statistical brief #102: hospitalizations related to diabetes in pregnancy, 2008. Healthcare Costs and Utilization Project. December 2010. www.hcup-us.ahrq.gov/reports/statbriefs/sb102.jsp. Accessed May 25, 2017.
7. American College of Obstetricians and Gynecologists. Practice bulletin #137: clinical management guidelines for obstetrician-gynecologists. Obstet Gynecol. 2013;122(2 Part 1):406-416.
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9. U.S. Preventive Services Task Force. Final recommendation statement: gestational diabetes mellitus, screening. December 2016.
www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/gestational-diabetes-mellitus-screening. Accessed May 25, 2017.
10. Aspart insulin. Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc. Updated May 9, 2017. https://online.lexi.com. Accessed May 25, 2017.
11. American Association of Clinical Endocrinologists. Management of pregnancy complicated by diabetes. http://outpatient.aace.com/diabetes-in-pregnancy/pregnancydm-s3-management. Accessed August 29, 2017.
12. Metformin. Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc. Updated May 19, 2017. https://online.lexi.com. Accessed May 25, 2017.
13. Gyburide. Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc. Updated May 12, 2017. https://online.lexi.com. Accessed May 25, 2017.
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