The purpose of this activity is to enable the learner to understand pregestational and gestational diabetes pathophysiology, diagnosis and management.
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Syllabus
Introduction
Pathophysiology
“Diabetes mellitus is a metabolic disorder characterized by progressive loss or dysfunction of pancreatic insulin-producing β-cells” (Remedi & Emfinger, 2016, para 1). The pancreas helps the body to use glucose for energy and regulate blood glucose (BG) levels (National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK], 2017b). There are three main types of diabetes mellitus: type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM). In T1DM, insulin is deficient in the body due to autoimmune destruction of the β-cells (Remedi & Emfinger, 2016). In T2DM, there is a” high insulin demand due to peripheral insulin resistance with compensatory β-cell expansion and hyperinsulinemia” (Remedi & Emfinger, 2016, para 2). In normal pregnancies, there is pancreatic β-cell hyperplasia, resulting in higher fasting and postprandial (after a meal) insulin levels. During pregnancy, higher levels of placental hormones secreted can interfere with how the body uses insulin, causing insulin resistance. The β-cell function is insufficient to overcome insulin resistance in patients with GDM (Garrison, 2015). GDM can also occur when the body is unable to produce the additional insulin needed during pregnancy.
In the literature, T1DM and T2DM are referred to as pregestational diabetes (PGD). PGD affects about 1-2% of pregnancies in the United States (Centers for Disease Control and Prevention [CDC], 2018). “Black and Hispanic women have higher rates of PGD during pregnancy” (CDC, 2018). About 10% of pregnancies every year in the United States are affected by GDM (American Diabetes Association [ADA], 2019b). “Asian and Hispanic women have higher rates of GDM” (CDC, 2019c, para 3). About 50% of women with GDM develop T2DM within ten years after delivery (International Diabetes Federation [IDF], 2019). “According to the IDF, the epidemiology of diabetes during pregnancy is unknown in many countries in the world” (Wahabi, Fayed, Esmaeil, Mamdouh, & Kotb, 2017, p. 1).
Risk Factors
Risk factors for developing GDM include:
- Previous pregnancy with GDM.
- Previous birth to a baby weighing more than 9 pounds.
- Overweight.
- Family history of T2DM.
- Polycystic ovary syndrome diagnosis.
- Races such as African American, Hispanic/Latino American, American Indian, Alaska Native, Native Hawaiian, or Pacific Islander (CDC, 2019c).
Issue
Diabetes during pregnancy can cause health issues for both the mother and the developing fetus (Sugrue & Zera, 2018). The risk of structural birth defects is increased in women with PGD, with most congenital defects occurring in the cardiovascular, central nervous, and musculoskeletal systems (Gabbay-Benziv, Reece, Wang, & Yang, 2015). Many women diagnosed with GDM experience pregnancy-related complications such as preeclampsia, macrosomia, and dystocia of labor (IDF, 2019). “Macrosomia is typically defined as fetal growth past 4,000 to 4,500 g regardless of gestational age, but there is no universally accepted definition" (American College of Obstetricians and Gynecologists [ACOG], 2016, para 1). "Dystocia of labor is abnormally slow progress of labor or difficult labor" (Olsen, 2017, para 2).
“Women with diabetes have high blood pressure more often than women without diabetes” (CDC, 2019b, para 6). Hyperglycemia damages blood vessels and nerves controlling the heart (NIDDK, 2017a). “Women who have high blood pressure or preeclampsia during pregnancy also are at greater risk of heart disease and stroke later in life” (ACOG, 2017, para 16).
In GDM, higher amounts of glucose are passed to the newborn via the placenta, and as a result, the extra glucose is stored as body fat, causing macrosomia (ACOG, 2017). Having an infant with macrosomia could lead to further complications for the mother, such as cesarean section, shoulder dystocia, postpartum hemorrhage, or severe vaginal lacerations (ACOG, 2017). GDM can cause complications for the child, such as respiratory distress syndrome, jaundice, hypoglycemia, and obesity or diabetes later in life (March of Dimes, 2019a)
Pregestational Diabetes Management of Care
Preconception counseling is important in women with T1DM as the hemoglobin A1C at conception can significantly affect pregnancy outcomes (Feldman & Brown, 2016). At high levels, glucose is teratogenic (Farahi & Zolotor, 2013). “Preconception care should include educating women about the impact of diabetes on pregnancy outcomes and the impact of pregnancy on diabetes, optimizing glycemic control, screening for vascular complications of diabetes, evaluating medication use, and encouraging effective family planning” (Farahi & Zolotor, 2013, p. 502; ACOG 2018b).
Complications During Pregnancy
Six to eight percent of pregnant women with PGD also have chronic hypertension, which is defined as hypertension prior to 20 weeks’ gestation (Sugrue & Zera, 2018). According to Kattah and Garovi (2013), the cause of the chronic hypertension is most likely due to a disruption of the angio-tension system as there is reduced renal vascular compliance and glomerular sclerosis caused by diabetes. Hypertension during pregnancy can lead to intrauterine growth restriction, fetal demise, superimposed preeclampsia, and preterm delivery. The goal of antihypertensive treatment in pregestational diabetes is to avoid blood pressures of systolic >160 mm Hg and diastolic >105 mm Hg. Safe antihypertensives include beta-blockers (e.g., labetalol [Trandate]), calcium-channel blockers (e.g., nifedipine [Procardia]), and alpha-2 agonists (e.g., methyldopa [Aldomet]) (Sugrue & Zera, 2018).
Research has shown that "pregnancy has been associated with exacerbation of diabetes-related complications, particularly retinopathy and nephropathy. Poorly controlled pregestational diabetes mellitus leads to serious end-organ damage that may eventually become life-threatening" (ACOG, 2018b, e231). Retinopathy can progress during pregnancy (ACOG, 2018b). Factors associated with progression include “the duration of diabetes, presence of hypertension, and adequacy of glycemic control” (Sugrue & Zera, 2018, p. 318). Women with PGD should be encouraged to obtain a baseline eye examination during the 1st trimester and should be closely monitored throughout the pregnancy (ACOG, 2018b). 2% to 5% of pregnancies in women with PGD also have nephropathy, which is microalbuminuria greater than 300 mg/24 hours with or without impaired renal function. End-stage renal disease is a concern with severe proteinuria in pregnancy (>3 g per 24 hours) or creatinine levels in excess of 1.5 mg/dL Aggressive management with antihypertensives can lead to better outcomes (Sugrue & Zera, 2018). A pregnant woman with diabetes is nearly ten times more likely to develop acute kidney injury (AKI) than a pregnant woman without diabetes (1.1% versus 0.1%) and those numbers have increased in recent years. This is important, because women with pregnant-related AKI have an in-hospital mortality rate of 2.6%, versus just 0.01% for pregnant women without AKI (Shah, Meganathan, Leonard, Christianson, & Thakar, 2019).
The risk of preeclampsia is increased in women with pregestational diabetes (ACOG, 2017). It is unknown if there is a pathophysiological link between preeclampsia and PGD. “Impaired vascular reactivity in pregnant women with T1DM makes them more susceptible to develop preeclampsia” (Kulshrestha & Agarwal, 2016, para 3). Due to the association of preeclampsia in women with PGD, the U.S. Preventive Services Task Force recommends the use of low-dose aspirin (81 mg/day) prophylactically after 12 weeks of gestation for those who are at high risk for preeclampsia (ADA, 2019a).
“Diabetic ketoacidosis (DKA) is l
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ife-threatening and affects 5-10% of women with T1DM” (Sugrue & Zera, 2018, p. 213). “DKA occurs at lower glucose levels because pregnancy is a ketosis-prone state” (Feldman & Brown, 2016, p. 76). Symptoms of DKA include polydipsia, polyuria, nausea, vomiting, malaise, headache with severe dehydration, hyperventilation, and altered mental status (Kulshrestha & Agarwal, 2016). Women with PGD should be taught how to check ketones in urine when feeling ill or during times of hyperglycemia.
“Elevated blood glucose levels at conception and during the early first trimester is associated with increased rates of congenital malformations” (Feldman & Brown, 2016, para 2). Research has shown that during the 1st trimester, “spontaneous abortion and congenital malformation, of the central nervous system, cardiac, gastrointestinal, and genitourinary tract, are significantly more incident with A1c >7%, and the risk is proportional to A1c” (Sugrue & Zera, 2018, p. 319). The incidence of congenital malformations was not different between T1DM and T2DM (Sugrue & Zera, 2018).
Abnormal fetal growth can occur, both macrosomia and intrauterine growth restriction (IUGR). Macrosomia may occur as the maternal hyperglycemia stimulates fetal hyperinsulinemia. Intrauterine growth restriction is defined as the fetal weight below the 10the percentile for gestational age. IUGR occurs because of placental dysfunction due to maternal vasculopathy (Gutaj & Wender-Ozegowska, 2016).
Research has shown that stillbirth rates in PGD are 4-5-fold the rates seen in the non-diabetic population (p<0.00). Higher A1c levels throughout the pregnancy are a risk factor for stillbirth (Mackin et al., 2019).
Blood Glucose Monitoring
Blood glucose monitoring (BGM) during pregnancy is recommended to achieve metabolic control and improve pregnancy outcomes (ADA, 2018). However, there is no specific approach on how to monitor BG levels. "A common approach is to check capillary glucose levels using a glucose meter in the fasting state, 1 or 2 hours after each meal, and before bed" (ACOG, 2018b, e231). A recent randomized control trial suggests continuous BGM may be beneficial to women with T1DM (Sugrue & Zera, 2018). The ADA (2019c) suggests the following targets for women with preexisting diabetes who become pregnant with individualization as needed:
- Before a meal (preprandial) and bedtime/overnight: 60-99 mg/dl
- Postprandial: 100-129 mg/dl
- A1C: less than 6% (ADA, 2019c).
Hypoglycemia is more frequent in pregnancy than at other times, particularly in women with T1DM (ACOG, 2018b).
Pharmacological Medications
For women with T1DM, pregnancy will affect the amount of insulin required.
“In the first trimester, there is often a decrease in total daily insulin requirements, and women, particularly those with T1DM, may experience increased hypoglycemia” (ADA, 2018, p.S140). After the 1st trimester of the pregnancy, the need for insulin will increase, especially during the last three months of pregnancy. The need for more insulin is caused by placental hormones for the fetus’ growth, but these placental hormones block the action of the mother's insulin (ADA, 2019c). Either multiple daily injections or a continuous subcutaneous insulin infusion can be used (Sugrue& Zera, 2018). Basal insulin delivered as intermediate-acting (hegedron [NPH] or lente [Humulin L]) or long-acting insulin (such as glargine [Lantus] or detemir [Levemir]) suppresses hepatic gluconeogenesis in the fasting state and is necessary for women with T1DM (Sugrue & Zera, 2019). The long-term risks of glargine (Lantus) in pregnancy are not known, as the US Food and Drug Administration (FDA) previously designated it as category C. Detemir (Levemir) was previously FDA category B in pregnancy (Feldman & Brown, 2016, p. 76). Bolus dosing of short-acting insulin, such as Lispro (Humalog) and Aspart (Novolog), is usually required with meals to mimic postprandial insulin secretion (Sugrue & Zera, 2018).
For women with T2DM on oral diabetic agents, the mother will typically need to switch to insulin as the safety of oral agents during pregnancy has not yet been established. The insulin resistance that occurs during pregnancy also decreases the effectiveness of oral diabetic agents (ADA, 2019c).
Fetal Assessment
Ultrasounds may be used to identify congenital anomalies early in pregnancy and to monitor fetal growth in the third trimester (ACOG, 2018b). In the second trimester, a fetal echocardiogram to rule out cardiovascular defects may also be appropriate if the A1c was elevated in the first trimester (Moore, 2018). Monitoring fetal well-being starting at 32 weeks with fetal movements, nonstress tests, contraction stress tests, and/or biophysical profiles, performed once or twice a week may be helpful to monitor women with PGD (ACOG, 2018b).
Intrapartum
"The ACOG and the Society for Maternal-Fetal Medicine have long discouraged nonindicated delivery before 39 weeks of gestation. However, there are a number of maternal, fetal, and placental complications in which either a late-preterm or early-term delivery is warranted. The timing of delivery in such cases must balance the maternal and newborn risks of late-preterm and early-term delivery with the risks associated with the further continuation of pregnancy" (ACOG, 2019, p. e152). Women with controlled PGD should deliver between 39 0/7 weeks and 39 6/7 weeks, whereas women with poorly controlled PGD should deliver between 36 0/7 weeks and 38 6/7 weeks (ACOG, 2019).
There is a risk of neonatal hypoglycemia if maternal hyperglycemia is present during labor. Evidence is limited on the best approach for intrapartum glycemic control; however,
intravenous insulin is often needed to maintain glucose at a goal of 70 to 110 mg/dL (Sugrue & Zera, 2018). Blood glucose checks may be monitored hourly (ACOG, 2018b).
Postpartum
“After delivery, insulin requirements decrease rapidly” (ACOG, 2018b, e238). Insulin requirements return to prepregnancy levels over the subsequent 1 to 2 weeks postpartum (Sugrue & Zera, 2018). Women should be encouraged to breastfeed, but the mother would need to be monitored for episodes of hypoglycemia (ACOG, 2018b). Research has shown breastfeeding may reduce insulin needs and have long-term benefits (Sugrue & Zera, 2018). “Breastfeeding increases insulin sensitivity and improves glucose metabolism in the mother” (Wein, 2015, para 1). Unfortunately, breastfeeding rates in women with T1DM may be lower than in the general population, likely due to both maternal and infant complications (Feldman & Brown, 2016, p. 76).
Contraception should be discussed with women who have PGD to prevent unplanned pregnancies. “Preferred postpartum contraceptive options in breastfeeding mothers include long-acting reversible contraceptives (copper or progestin intrauterine devices, etonogestrel implants) and progestogen-only pills” (Sugrue & Zera, 2018, p. 324).
Gestational Diabetes Management of Care
Current ADA guidelines recommend selective screening of high-risk women for GDM, whereas ACOG guidelines advise universal screening (Rani & Begum, 2016). “The US Preventive Services Task Force recommends screening for GDM after 24 weeks of pregnancy for asymptomatic women with no previous diagnosis of PGD” (Moore, 2017, para 6). Women with high-risk factors may be tested prior (U.S. Preventive Services Task Force, 2016). In the United States, the two-step screening system is used: the glucose challenge test (GCT) as a baseline and the oral glucose tolerance test (OGTT) for any abnormal GCT results.
In the 2-step approach, the 50-g glucose screening is performed gestation in a nonfasting state (U.S. Preventive Services Task Force, 2016). A blood draw is done one hour after drinking a 50-g glucose drink. If the plasma glucose at one hour is ≥ 140mg/dl (7.8mmol/L), then the mother will proceed to the 100g OGTT (Rani & Begum, 2016). Some guidelines suggest a cut-off of 130 mg/dl for the GCT, which is more sensitive but inherently less specific, leading to more false-positive but less false negatives (Garrison, 2015).
The OGTT is done after fasting for 8 hours. A fasting BG level is drawn, and then the mother drinks the 100-g glucose liquid. Blood is drawn every hour for two to three hours afterward (NIDDK, 2017c). According to the two primary sets of criteria (Carpenter and Coustan/National Diabetes Data Group), GDM is diagnosed when at least two plasma glucose readings are at least:
At three hours: 140/145 mg/dl (7.8/8.0 mmol/L) (Garrison, 2015; Rani & Begum, 2016).
In Europe, the one-step approach is most commonly used (see Table 1 below). A patient who is fasting ingests 75 g of glucose, and GDM is diagnosed if BG levels at one and two hours later reach certain target levels (Busko, 2014). There are varied diagnostic and screening tools used throughout the world. Table 1 below discusses the most commonly used guidelines for the diagnosis of GDM from the World Health Organization, ACOG, Canadian Diabetes Association, and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) with values listed in mmol/L.
Blood Glucose Monitoring
BG monitoring is usually required for mothers with GDM. The ADA and the ACOG suggest the following target BG levels for women who develop GDM. Individualized glycemic goals may vary slightly.
- Preprandial: 95 mg/dl or less
- One hour postprandial: 140 mg/dl or less
- Two hours postprandial: 120 mg/dl or less (ADA, 2019d; ACOG, 2019).
“No data suggest the superiority of one-hour versus two-hour postprandial monitoring, so either is acceptable” (Garrison, 2015, p. 461).
Diet and Exercise
Most pregnant women with GDM can be managed with a healthy diet and regular exercise, however, some women do need to take insulin (CDC, 2019a). “Women with GDM should receive individualized nutrition counseling from a registered dietitian” (Garrison, 2015, p. 461). Pregnant women with GDM should avoid single large meals and foods with a large percentage of simple carbohydrates (Moore, 2018). The nutritionist should provide adequate calorie intake to promote fetal/neonatal and maternal health, achieve glycemic goals, and promote appropriate gestational weight gain (Garrison, 2015). “There is no definitive research that identifies a specific optimal calorie intake for women with GDM or suggests that their calorie needs are different from those of pregnant women without GDM” (ADA, 2018, para 16).
ACOG recommends regular moderate exercise inpatients diagnosed with GDM. Most experts recommended at least 30 minutes of moderate-intensity physical activity five days or more a week, or a total of 150 minutes weekly (ACOG, 2017; CDC, 2019b). Women with GDM who participate in aerobic or resistance training can improve glycemic control (Colberg, Castorino, & Jovanovič, 2013).
Pharmacological Medications
In GDM, early intervention with medications is important to achieving a good outcome if diet and exercise fail to provide adequate glycemic control. The standard and preferred treatment for GDM is insulin, largely due to its efficacy and safety (ACOG, 2018a). Insulin is not transferred through the placenta or into breast milk and, therefore, remains the optimal treatment during pregnancy and lactation (Kalra, Gupta, Singla, & Kalra, 2015). “Currently, rapid-acting insulin analogs are preferred over regular insulin in pregnancy as they are associated with less risk of hypoglycemia and may also provide better postpartum BG control” (Alfadhli, 2015, para 18).
Treatment with the oral agents glyburide (Diabeta) and metformin (Glucophage) has been gaining in popularity (Moore, 2018). However, oral agents cross the placenta, and long-term safety data is not available, so these should not be considered first-line (American Association of Diabetic Educators, 2018; ADA, 2019d). The FDA has not approved oral diabetic agents for the treatment of diabetes in pregnancy (Kalra et al., 2015). Metformin (Glucophage) is a reasonable alternative for women who decline insulin therapy, cannot afford insulin, or if health care providers believe the woman would be unable to administer insulin safely (ACOG, 2018a). It was associated with a higher rate of prematurity when compared to insulin but may lead to less neonatal hypoglycemia and reduced weight gain in mothers (ADA, 2019d). Glyburide (Diabeta) should not be recommended as the first choice of pharmacological treatment as studies do not indicate equivalent outcomes to insulin (ACOG, 2018a). It was also associated with increased neonatal hypoglycemia and macrosomia (ADA, 2019d). Health care providers should provide counseling on the lack of long-term safety of glyburide (Diabeta) and metformin (Glucophage) (Garrison, 2015).
Fetal Assessment
There is no consensus on the optimal approach for antenatal testing in GDM pregnancies. “Antenatal testing is commonly performed in women who require medication for GDM, although data supporting this practice are limited to older observational studies” (Garrison, 2015, p. 463). “ACOG recommends that clinicians perform antenatal testing per local practice patterns and may include twice weekly nonstress tests or weekly biophysical profiles beginning at 32 to 34 weeks of gestation” (as cited in Garrison, 2015, p. 463). ACOG recommends health care providers assess fetal growth in women with GDM late in the third trimester, stating that ultrasonography or clinical examination is appropriate (Garrison, 2015).
Intrapartum
Delivery before 39 weeks is not recommended for women with controlled gestational diabetes (ACOG, 2019). ACOG has made the following recommendations for the suggested timing of delivery for women with GDM (See Table 2).
During labor and delivery, maintaining euglycemia can minimize risks of neonatal hypoglycemia and lactic acidosis. Insulin during labor and delivery is not usually required for women with diet-controlled GDM. There is no consensus on intrapartum management of BG among women receiving insulin. Still, BG levels should be monitored every one to two hours during active labor, and 5% dextrose or insulin may need to be infused to maintain BG levels between 70 and 110 mg/ dL (3.9 and 6.1 mmol/ L) (Garrison, 2015).
Health care providers should prepare to manage shoulder dystocia at the time of delivery. Shoulder dystocia can occur when one or more of the baby’s shoulders gets stuck in the mother’s pelvis during labor and birth (March of Dimes, 2019b).
Postpartum
GDM usually resolves in the postpartum period, but women are at increased risk for developing T2DM (U.S. Preventive Services Task Force. (2016). It is recommended that women with GDM be screened at 4 to 12 weeks postpartum, and every three years thereafter, for abnormal glucose metabolism (ACOG, 2017; ADA 2019c). “15% to 60% of women with GDM develop T2DM within 5 to 15 years postpartum” (U.S. Preventive Services Task Force, 2016, Discussion section, para 2). Women with GDM commonly revert to normal glucose tolerance after pregnancy. Women should also be encouraged to breastfeed, as there are both short-term and long-term benefits. Research has shown that breastfeeding is associated with improvements in glucose and lipid metabolism along with a reduced risk of T2DM in women with a history of GDM (Much, Beyerlein, Roßbauer, Hummel, & Ziegler, 2014). “Research has estimated that women who exclusively breastfed or mostly breastfed were about half as likely to develop T2DM as those who didn’t breastfeed” (as cited in Wein, 2015, para 4).
Implications for Evidence-Based Nursing Care
Nurses can help reduce negative outcomes by assessing the mother for barriers to managing PGD and GDM, therefore achieving good glycemic control. The most common barriers are knowledge gap, patient nonadherence, and financial constraints (Bell, 2015). Proper education about the disease pathophysiology, ways to manage PGD and GDM, and possible adverse effects to the mother and fetus are needed to close the knowledge gap. The mother may be nonadherent to the treatment for multiple reasons. Is the mother able to calculate the insulin dose? Can the mother count carbohydrates correctly? Errors in carbohydrate counting and incorrect insulin doses can lead to hypoglycemia (Bell, 2015). The nurse may need to guide the mother on how to obtain health care coverage. Low-income women are usually eligible for health insurance from local, state, or federal health programs during pregnancy (Bell, 2015).
Future Research
Diabetes during pregnancy is a global health issue because of the high prevalence and potential impact on the health of mothers and their children (Koning, Hoogenberg, Lutgers, Berg, & Wolffenbuttel, 2016; Wahabi et al., 2017). “Studying any drug for safety and efficacy in pregnancy is always difficult due to ethical concerns” (Kalra et al., 2015, para 2). More research is needed to understand the long-term safety of the use of oral agents during pregnancy. There is not much data on the exposure of a fetus to the mother’s use of oral diabetic agents during pregnancy as well as during breastfeeding. Long-term safety is in question.
There also needs to be a consensus reached for optimal screening as it is controversial in the United States. In research by Metzger, Lowe, Dyer, et al., women with elevated glucose levels on the 75-g test have an increased risk of adverse pregnancy outcomes (as cited in Garrison, 2015). Still, no clinical trials have demonstrated that treatment of GDM in these women who have tested with the 75-g test improves pregnancy outcomes (Garrison, 2015).
No high-quality data exist for the optimal diet for women diagnosed with GDM (Garrison, 2015). Current recommendations are to limit carbohydrate intake to 33%-40% of intake (Garrison, 2015). Studies show promising results on glycemic control and the reduced risk of later developing T2DM, but there is a need for further investigation of the benefits and disadvantages of dietary carbohydrate restriction in GDM both during pregnancy and afterward (Koning et al., 2016).
Physical activity is safe during pregnancy. Further research is needed to determine the optimal type, duration, and intensity of exercise during pregnancy, particularly for women with GDM (Wang et al., 2016).
“The Diabetic Pregnancy Study Group (DPSG) of the European Association for the Study of Diabetes aims to further research and promote education to improve the management of pregnant women with diabetes and their offspring. Every ten years, DPSG conducts an audit meeting to review the achievements of the previous decade and to set the directions for research and clinical practice improvements for the next decade”. Figure 1 discusses the challenges for the next decade.
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