Diabetes in Pregnancy

DIABETES IN PREGNANCY

COURSE DESCRIPTION

Diabetes during pregnancy can provide a special challenge to the patient and her healthcare providers. The effects of poorly controlled blood glucose levels can result in life-threatening effects for both the mother and the fetus.

The outcome of this course is for the learner to describe the types of diabetes, the metabolic changes that occur during diabetic pregnancies, and treatment options (including diet, exercise, and medication).

COURSE OBJECTIVES

Upon completion of this course, you will be able to do the following:

1. Define diabetes. 2. Identify the major health impacts of diabetes. 3. Explain the role of hormones and other body chemicals on insulin production. 4. Briefly describe the pathophysiology of diabetes. 5. Identify the five main types of diabetes and describe their major characteristics. 6. Describe the metabolic changes that occur in a normal pregnancy. 7. Identify maternal complications from diabetes. 8. Identify fetal and neonatal effects of diabetes. 9. Describe the major characteristics of pregestational diabetes. 10. Identify White’s main classifications of diabetes in pregnancy. 11. Identify key components of screening and treatment for the patient with GDM. 12. Describe general management techniques for the pregnant woman with diabetes, including diet, exercise, and medication therapies. 13. Identify tests used to assess placental function and fetal well-being. 14. Describe major management issues for the pregnant woman during the intrapartum, labor and delivery, and postpartum periods. 15. Describe new therapies for the pregnant woman with diabetes, including oral hypoglycemic agents, insulin pump therapy, and islet cell transplantation.

INTRODUCTION

Most of the food we eat is converted by our bodies into glucose—fuel for our cells. If that glucose cannot be utilized, as in untreated or uncontrolled diabetes, the cells “starve.” Glucose and fats remain in the bloodstream and, over time, cause damage to vital organs such as the heart, eyes, and kidneys (Centers for Disease Control and Prevention [CDC], 2017).

In pregnancy, diabetes can result in serious complications to the mother and/or the fetus and neonate.

• Diabetes in pregnancy complicates 2% to 10% of all pregnancies, but these statistics are probably understated.

• Although maternal and fetal complications can be life threatening, early and proper intervention can be powerful (Buchanan, 2016).

Gestational diabetes mellitus (GDM) can often be controlled through eating a proper diet and exercising regularly, although insulin injections may be necessary. GDM usually goes away after pregnancy but not always, and many women who have GDM develop Type 2 diabetes later in life (CDC, 2017).

WHAT IS DIABETES?

Pillitteri (2013) defines diabetes mellitus as an endocrine disorder in which the pancreas cannot produce adequate insulin to regulate body glucose.

According to the CDC (2017), diabetes is a group of diseases marked by high levels of blood glucose resulting from defects in insulin production, insulin action, or both.

The Scope of the Problem

Diabetes mellitus is a growing public health problem both nationally and internationally (CDC, 2017; International Diabetes Federation, 2017; World Health Organization [WHO], 2017).

• Approximately 8.3% of the population of the United States and the world have diagnosed or undiagnosed diabetes. This is probably an underreported number since almost half of the people with diabetes do not know they have it.

• As of 2045, there are expected to be more than 629 million people worldwide living with diabetes.

• Diabetes causes 4 million deaths every year and is the 7th leading cause of death in the United States (CDC, 2017), and by 2030 it is expected to be the 7th leading cause of death worldwide.

All types of diabetes are now being found in younger and younger individuals. One type, type 2 diabetes, is especially linked to obesity and physical inactivity. Yet most Americans lead sedentary lives with little or no physical exertion. Roughly 27% of adults do not engage in any physical activity while another 28% do not regularly exercise (CDC, 2017; Flood & Constance, 2002).

The health impact of diabetes is tremendous. Studies have found the following (American Diabetes Association, 2018; CDC, 2017; WHO, 2017):

• The death rate among middle-aged people with diabetes is twice that of middle-aged people without diabetes.

• Adults with diabetes have heart disease death rates two to four times higher than adults without diabetes. Heart disease is the leading cause of diabetes- related deaths.

• The risk of stroke is two to four times higher in individuals with diabetes.

• Diabetes is the leading cause of new cases of blindness in adults 20 to 74 years of age. Each year, more than 12,000 to 24,000 people become blind because of diabetic eye disease.

• Diabetes is the leading cause of end-stage renal disease, accounting for 44% of new cases annually.

• About 60% to 70% of people with diabetes have mild to severe forms of nervous system damage (including impaired sensation or pain in their hands or feet, slowed digestion, and carpal tunnel syndrome).

• The majority of lower-limb amputations throughout the world occur in individuals with diabetes.

• Diabetics are more likely than those without the disease to suffer from many other illnesses and infections such as flu and pneumonia.

• Women with diabetes are two to three times more likely to experience a newborn death than those women without diabetes.

Diabetes costs the U. S. healthcare system more than $245 billion annually related to disability, loss of work, and premature mortality. The full extent of the disease is hard to measure, since death records often do not reflect the role of diabetes in the cause of death (CDC, 2017).

Etiology and Pathophysiology of Diabetes

Mattson and Smith (2015) define diabetes as a chronic, systemic endocrine disorder of insulin production or of the body’s response to insulin, which is a water-soluble, anabolic hormone secreted by the beta cells of the islets of Langerhans in the pancreas.

Insulin is a protein whose primary function is to promote the metabolism of carbohydrates, proteins, lipids, and nucleic acids (Pillitteri, 2013). Insulin acts as a “key” to unlock the cell membrane, allowing glucose, amino acids, and electrolytes into the cells of cardiac, skeletal, and adipose tissues. Brain cells, erythrocytes, leukocytes, intestinal mucosa, and the epithelium of the kidney need glucose to survive but they can survive in an insulin-deficient environment (Pillitteri, 2013).

The exact etiology of diabetes is not known but the current belief is that an autoimmune destruction of the islet cells occurs in individuals who are predisposed to the disease (Pillitteri, 2013).

The actual amount of insulin secreted by the pancreas is regulated by serum (blood) glucose levels. When serum glucose levels are greater than 100 mg/dL, beta cells increase their production of insulin. When serum glucose levels are lowered, the production of insulin decreases (Pillitteri, 2013).

In diabetes, the pancreas cannot produce adequate insulin to regulate body glucose.

While the pancreas is primarily responsible for the production of insulin, the following additional hormones are also necessary for its secretion (Pillitteri, 2013):

• Gastrin—a gastrointestinal hormone that increases when the stomach is full, stimulating the pancreas to produce more insulin • Glucagon • Cortisol • Progesterone • Estrogen

Epinephrine and norepinephrine inhibit the secretion of insulin (Pillitteri, 2013).

When the amount of insulin in the body is insufficient, glucose cannot be used by the cells. • The cells continue to demand glucose, and the liver responds by converting glycogen to glucose to increase the serum glucose levels.

• However, that glucose cannot be utilized because of the lack of adequate insulin.

• Blood glucose levels continue to rise as the cells continue to “request” glucose and the liver continues to try to meet that need.

• When serum glucose levels reach 150 mg/100 dL (normal serum glucose levels are 80 to 120 mg/dL), the kidneys attempt to lower the serum glucose levels by excreting glucose in the urine (glycosuria).

• Because of the osmotic action of glucose, the kidneys are unable to absorb the normal amount of fluid and large quantities of fluid are lost in the urine (polyuria) (Pillitteri, 2013).

As this process continues, dehydration occurs and the blood serum becomes concentrated.

• Blood volume may decrease, blood flow decreases, and the body cells become oxygen starved.

• Anaerobic metabolism results as large stores of lactic acid pour out of the muscles and into the bloodstream.

• The body begins to utilize fat stores as an energy source, a metabolic process that results in the release of ketone bodies into the bloodstream.

• Because they are acidic, lactic acid and ketone bodies lower the blood pH and the individual develops metabolic acidosis (Pillitteri, 2013).

Next, the body utilizes its protein stores in an attempt to obtain any available energy source for its cells.

• Protein destruction (catabolism) reduces the amount of protein available to the cells, the cells can be destroyed, and sodium and potassium are excreted from the body.

• In the long term, these processes cause vascular narrowing and cardiovascular damage, kidney and retinal dysfunction, and increased blood pressure (Pillitteri, 2013).

• Despite this dramatic process, diabetes is often asymptomatic in its early stages (Mattson & Smith, 2015).

However, when symptoms appear, they may include some or none of the following (CDC, 2017):

• Frequent urination • Excessive thirst • Unexplained weight loss • Extreme hunger

• Sudden vision changes • Tingling or numbness in their hands or feet • Fatigue much of the time • Very dry skin • Sores that are slow to heal • Increased number of infections

QUESTIONS FOR REFLECTION

Why do you think diabetes has become such a tremendous health concern in the last decade?

What do you think can be done to reduce the effect of diabetes on the healthcare system in the United States?

TYPES OF DIABETES

Diabetes is classified according to the age of onset, the type of management necessary (diet versus insulin), the duration of the disease, and the presence of any vascular complications (Mattson & Smith, 2015).

There are five main types of diabetes. A brief description of each is presented below. An extensive discussion of gestational diabetes follows (CDC, 2017; Mattson & Smith, 2015; WHO, 2017):

1. Type 1 diabetes, previously called insulin- dependent diabetes mellitus (IDDM) or juvenile- onset diabetes

2. Type 2 diabetes, previously called noninsulin- dependent diabetes mellitus (NIDDM) or adult- onset diabetes

3. Impaired glucose tolerance (IGT)

4. Impaired fasting glucose (IFG)

5. Gestational diabetes mellitus (GDM)

The first three types can develop at any time in life, irrespective of pregnancy. They are referred to as pregestational diabetes. The fifth type, gestational diabetes mellitus, occurs after the onset of pregnancy. Of diabetes seen during pregnancy, 10% is pregestational and the remaining 90% is gestational diabetes (El-Sayed & Lyell, 2001).

Type 1 Diabetes

Type 1 diabetes (previously called insulin-dependent diabetes mellitus [IDDM] or juvenile-onset diabetes) usually starts before age 30 but can occur at any age. The onset of symptoms is usually abrupt and requires prompt medical treatment with insulin. Type 1 diabetes develops when the body’s immune system destroys pancreatic beta cells (the only cells in the body that make the hormone insulin). People with type 1 diabetes must have insulin delivered via injection or pump in order to survive.

Approximately 5% to 10% of all individuals with diabetes have type 1 diabetes. Risk factors are not well defined for this type of diabetes but are thought to be autoimmune, genetic, and environmental factors. There is no known way to prevent type 1 diabetes and no known cause (American Diabetes Association, 2015a; CDC, 2017; Mattson & Smith, 2015; WHO, 2017).

Type 2 Diabetes

Type 2 diabetes (previously called noninsulin-dependent diabetes mellitus [NIDDM] or adult-onset diabetes) usually develops after age 40 but is also occurring at a much younger age. The disease has many of the same symptoms as type 1 diabetes but an individual may also be symptom-free for many years, with a slow onset and gradual progression of symptoms. Often, the complications of the disease are the first sign of its presence. The incidence of type 2 diabetes increases with age and it accounts for approximately 90% to 95% of all individuals diagnosed with diabetes (CDC, 2017; Mattson & Smith, 2015; WHO, 2017).

Risk factors for this type of diabetes include the following (U.S. Department of Health and Human Services [USDHHS], 2016; WHO, 2017): • older age • obesity • a family history of diabetes • a prior history of gestational diabetes • impaired glucose tolerance • physical inactivity • race/ethnicity • hypertension • cigarette smoking

African Americans, Hispanic/Latino Americans, American Indians, and some Asian Americans, Native Hawaiians, and Pacific Islanders are especially susceptible to type 2 diabetes. They are more than twice as likely as their non-Hispanic white counterparts to have diabetes and twice as likely to die from diabetes than non-Hispanic whites. Data are limited for this population (USDHHS, 2016).

It is usually managed with diet and exercise, although oral hypoglycemic medications or insulin may be required if hyperglycemia persists despite nutritional and exercise

Impaired Glucose Tolerance (IGT) or Prediabetes

This category of diabetes, often called prediabetes, accounts for approximately 1% to 2% of all diagnosed cases of diabetes. Approximately 10% to 15% of adults in the United States have IGT when tested by oral glucose challenge (Rao, Disraeli, & McGregor, 2004).

IGT is defined as a 2-hour glucose level of 140 to 199 mg per dL on the 75-g oral glucose tolerance test; this is above normal levels but below the level that is diagnostic for diabetes (Rao, Disraeli, & McGregor, 2004).

Impaired glucose tolerance is characterized by hyperglycemia at a lower level than the level diagnostic for diabetes. The symptoms of diabetes are not present. However, the condition does carry some risk. For example, infants born to women with IGT are at an increased risk for macrosomia (Mattson & Smith, 2015).

People with prediabetes have a 150% greater risk of cardiovascular disease compared to people with normal blood glucose levels (American Diabetes Association, 2015a; Rao, Disraeli, & McGregor, 2004).

Diabetes can result from other conditions such as specific genetic syndromes, pancreatic disease, hormonal disease, drug or chemical exposure, insulin receptor abnormalities, surgery, drugs, malnutrition, infections, and other illnesses.

Impaired Fasting Glucose

Impaired fasting glucose and impaired glucose tolerance form an intermediate stage in the natural progression of diabetes mellitus. Approximately 10% to 15% of adults in the United States are believed to have this condition. It includes individuals who have fasting plasma glucose values of 110 to 125 mg/dL (Rao, Disraeli, & McGregor, 2004).

At this time, scientists are trying to understand how to determine which of these individuals will develop diabetes later in life and how such a progression can be prevented.

Gestational Diabetes Mellitus (GDM)

Approximately 4% to 8% of all women who do not begin their pregnancies with diabetes become diabetic during its course (Setji, Brown, & Feinglos, 2005).

At about the 24th week of pregnancy, the placenta begins producing large quantities of hormones that cause insulin resistance. This results in a condition called gestational diabetes mellitus, or GDM (Mattson & Smith, 2015; Pillitteri, 2013).

Approximately 90% to 95% of pregnant women with diabetes have GDM (Langer, 2016). While no one knows its exact cause, GDM is thought to result from a combination of excessive insulin resistance common during pregnancy and inadequate insulin response to carbohydrates (CDC, 2017; Pillitteri, 2013).

Risk factors for GDM include the following: • obesity • family history of diabetes • race/ethnicity (especially among African Americans, Hispanic/Latino Americans, and American Indians)

The symptoms of GDM are mild and often fade once the pregnancy has ended, but 50% to 60% of women with GDM risk developing type 2 diabetes later in life (Pillitteri, 2013).

QUESTIONS FOR REFLECTION

What are the types of diabetes?

How do they differ in their onsets, symptoms, and potential health effects?

DIABETES DURING PREGNANCY

Now that a general overview of diabetes has been presented, the remainder of this course will focus on how diabetes impacts pregnancy.

Metabolic Changes Caused by Pregnancy

During a normal pregnancy, changes in carbohydrate, protein, and fat metabolism are profound, influenced by the developing fetus and the production of placental hormones.

In the first half of pregnancy, a woman’s body enters an anabolic phase characterized by the following events (Mattson & Smith, 2015; Simpson & Creehan, 2013):

• Increased estrogen and progesterone secretion

• Increased growth of pancreatic beta cells

• Increased secretion of insulin

• Increased uptake and storage of glycogen and fat in the liver and body tissues

During the second half of pregnancy, the woman enters a catabolic phase characterized by the following events (Mattson & Smith, 2015; Setji, Brown, & Feinglos, 2005; Simpson & Creehan, 2013):

• Increased production of human placental lactogen (HPL), also called human chorionic somatomammotropin • Elevated levels of estrogen, progesterone, blood triglycerides, free fatty acids, and serum cortisol • Decreased glycogenesis • Increased lipolysis, gluconeogenesis, and ketone production • Increased maternal lipolysis resulting in a starvation-like state for the mother

The fetus utilizes glucose and amino acids (which are readily transported across the placenta from the maternal circulation) for growth. The fetal demand for glucose in the late third trimester is met by the increase in maternal hepatic glucose production (Simpson & Creehan, 2013; Troiano, Harvey, & Chez, 2013).

Maternal insulin, however, is not readily transported across the placenta.

Pregnancy has been characterized as a “diabetogenic state” because maternal glucose levels are lowered, resulting in maternal hypoglycemia and a lower fasting blood glucose level. During the first trimester, maternal fasting blood glucose levels are 10% to 20% lower than before pregnancy, but fetal glucose demands are also lower (Dunne, 1999; Mattson & Smith, 2015; Pillitteri, 2013; Simpson & Creehan, 2013).

In a normal pregnancy, insulin resistance or a slight degradation of insulin prevents the woman’s blood glucose from falling to very low levels, despite the increased insulin that is produced (Pillitteri, 2013).

Blood Glucose Values During Pregnancy Ideal (Mattson & Goal (Mattson & Goal (ACOG, Smith, 2015, p. 475) Smith, 2015, p. 475) 2005) (if there is no diabetes or carbohydrate intolerance during pregnancy) Fasting blood sugar 55–60 mg/dL < 90 mg/dL < 105 mg/dL 1-hour postprandial 120–140 mg/dL < 140 mg/dL <155 mg/dL Mean blood glucose 84 mg/dL < 100 mg/dL <135 mg/dL Glycosylated 2–5% < 7% ≤ 6% hemoglobin (Hgb A1c)

Diabetic Concerns during Pregnancy

Gestational diabetes mellitus is caused by abnormalities in at least three aspects of fuel metabolism (Keely & Barbour, 2016):

1. Insulin resistance 2. Impaired insulin secretion 3. Increased hepatic glucose production

Prior to the synthetic production of insulin in 1921, many women with diabetes either (Hadden, 2016; Pillitteri, 2013)

• failed to reach childbearing age, • were infertile, • possibly had more congenital malformations and preeclampsia, or • had spontaneous abortions early in the pregnancy.

Since this disorder is now controllable, concerns with diabetes during pregnancy focus on four major areas (Pillitteri, 2013):

1. How to maintain good glucose control during pregnancy in the woman with diabetes

2. How to protect the fetus in utero from the adverse effects of diabetes

3. How to care for the infant during the first 24 hours after birth during the time when the infant’s insulin-glucose regulatory mechanism stabilizes

4. How to develop an effective reproductive planning strategy

Maternal Complications of Diabetes

Even when a diabetic woman has successfully controlled her glucose and insulin metabolism before the pregnancy, she is likely to experience less control during the pregnancy since all women undergo numerous changes in their glucose and insulin regulation as the pregnancy progresses. © ALLEGRA Learning Solutions, LLC All Rights Reserved

The reasons for this include the following (Pillitteri, 2013):

• Increased glomerular filtration causing slight glycosuria

• Increased resistance to insulin (due to the interactions of multiple hormones)

• The presence of placental insulinase (which may cause increased breakdown or degradation of insulin)

For a woman’s health to remain optimal, the following maternal complications of diabetes must be prevented (Gunton et al., 2000; Mattson & Smith, 2015; Pillitteri, 2013; Setji, Brown, & Feinglos, 2005; Troiano, Harvey, & Chez, 2013):

• Hyperemesis gravidarum • Increased risk of hypoglycemia (especially in the first trimester) • Increased risk of ketonuria (especially in the second trimester) • Increased risk of infection (including urinary tract infections, monilial [yeast] infection, chorioamnionitis, postpartum endometritis) • Progression of vascular disease • Polyhydramnios • Preeclampsia or pregnancy-induced hypertension • Increased maternal mortality (from ischemic heart disease, ketoacidosis, hypoglycemia, and labor disturbances) • Retinopathy (with an incidence of 20% to 27% in women with type 1 diabetes) • Nephropathy (strongly associated with poor pregnancy outcome) • Large-for-gestational-age (greater than 10 lbs) or macrosomic infant • Increased risk for shoulder dystocia • Increased risk of cesarean delivery • Postpartum hemorrhage and subsequent anemia (secondary to birth trauma, uterine atony, fetal macrosomia, polyhydramnios, infection)

The risks associated with diabetes in pregnancy (nephropathy, hypertension, and heart disease) are far more related to metabolism regulation than to genetic characteristics of the disease. In addition, Pederson’s signs are associated with a poor pregnancy outcome.

Pederson’s signs include the following (Mattson & Smith, 2015):

1. Diabetic ketoacidosis affects 1% of diabetic pregnancies and is associated with hyperemesis gravidarum, tocolytic therapy, infections, corticosteroid use, and insulin pump failure.

2. Preeclampsia (pregnancy-induced hypertension) complicates 10% to 15% of type 1 diabetic pregnancies compared with 5% of nondiabetic pregnancies.

3. Maternal infections (especially pyelonephritis) are often related to poor metabolic control; 80% of type 1 diabetic pregnancies have at least one episode of infection compared to 26% of nondiabetic pregnancies.

4. Maternal neglect is usually associated with poor glucose control and multiple maternal and fetal complications.

Diabetic Ketoacidosis

Diabetic ketoacidosis is a potentially life-threatening complication of uncontrolled diabetes. It is more common in pregnant women with pregestational diabetes than in women with gestational diabetes (Simpson & Creehan, 2013). Its incidence has been reduced in part because of the ability of women to better control their diabetes.

The clinical symptoms of diabetic ketoacidosis include the following (Simpson & Creehan, 2013):

• Vomiting • Kussmaul respirations • Fruity breath odor • Anorexia • Abdominal pain • Dehydration (as much as 10 liters) • Polyuria • Polydipsia • Weakness • Malaise • Headache • Hyperventilation • Plasma glucose levels > 300 mg/dL • Arterial pH < 7.3 • Plasma bicarbonate level < 15 mEq/L • Elevated hematocrit • Elevated urea nitrogen • Elevated leukocytes

Treatment involves aggressive management of the dehydration, hyperglycemia, and electrolyte imbalance. Intravenous access should be obtained immediately to increase

© ALLEGRA Learning Solutions, LLC All Rights Reserved intravascular volume, improve tissue perfusion, improve insulin delivery, and lower blood glucose. Insulin should be administered and a Foley catheter inserted to closely monitor the urine output. A pulse oximeter may be used to monitor oxygen levels and a continuous electrocardiograph (ECG) might be obtained to detect any changes associated with hypokalemia. The fetus must be monitored continuously (Simpson & Creehan, 2013).

QUESTIONS FOR REFLECTION

What are Pederson’s signs?

Why are they important in the clinical care of the gestational diabetic patient?

Effects of Diabetes on the Fetus and Neonate

In about 25% of diabetic women, the fetus experiences hyperglycemia secondary to maternal hyperglycemia, and hydramnios may occur. This condition is due to increased fetal urine production as a result of elevated maternal serum glucose levels. Hydramnios places the woman at risk for preterm labor or amniocentesis and possible infection (Pillitteri, 2013).

In addition, the fetus is at risk for the following (CDC, 2017; Dunne, 1999; Gunton et al., 2000; Langer, 2016; Pillitteri, 2013; Setji, Brown, & Feinglos, 2005; Troiano, Harvey, & Chez, 2013):

• Asphyxia and acidosis

• Spontaneous abortion

• Increased risk of congenital malformations and anomalies of the cardiac, skeletal, neurological, genitourinary, and gastrointestinal systems (especially during the first 6 to 8 weeks of gestation, when organogenesis occurs)

• Macrosomia (fetal weight > 4,000 grams), which occurs in approximately 26% of infants and is related to fetal hyperinsulinemia (the excess insulin produced by the fetus to counteract maternal hyperglycemia stimulates growth)

• Intrauterine growth retardation (IUGR) related to maternal vascular disease and decreased placental perfusion (occurs in approximately 20% of diabetic pregnancies)

• Birth trauma related to macrosomia (such as shoulder dystocia)

• Stillbirth (especially after 36 weeks’ gestation) related to poor glucose control, fetal macrosomia, maternal vascular disease, ketoacidosis, and pregnancy- induced hypertension

• Prematurity related to preterm birth associated with maternal complications

• Respiratory distress syndrome (caused by fetal hyperinsulinemia from maternal hyperglycemia and resulting in a decrease in lung surfactant production)

• Hypoglycemia (especially in the first 24 hours of life, with an incidence of 25% to 40%)

• Hypocalcemia (due to diffusion of calcium from intracellular to extracellular fluid during periods of acidosis)

• Hypomagnesemia (due to greater renal loss of magnesium associated with polyuria resulting from hyperglycemia)

• Hyperbilirubinemia (due to polycythemia and birth trauma)

• Polycythemia (due to chronic intrauterine hypoxia)

• Potential problems related to behavioral and intellectual development of the child due to neurological and cognitive dysfunction

Complications are worse in those women who do not plan their pregnancies, especially if they have type 1 diabetes. Unplanned pregnancies occur in approximately 67% of women with diabetes (American Diabetes Association [ADA], 2002a; Troiano, Harvey, & Chez, 2013). Pregnancy planning is more prevalent in those women with type 2 diabetes, as well as those women who are older, do not smoke, have had diabetes for only a short time, and who are non-Caucasian (Gunton et al., 2000; Howorka et al., 2001).

PREGESTATIONAL DIABETES

Pregestational diabetes is a chronic autoimmune disorder resulting from the malfunction of the beta cells of the pancreas. A woman’s predisposition to this disorder is genetically determined (Mattson & Smith, 2015). It can present as any of the first three types of diabetes previously described (type 1, type 2, and IGT) and affects more than 10,000 women each year.

Reproductive Planning

Reproductive considerations are a relatively recent concern for the woman with diabetes. No contraceptive methods are specifically contraindicated in women with diabetes (ADA, 2002a).

• However, birth control pills carry the risk of increased blood glucose levels, since the progesterone interferes with insulin activity and the estrogen may increase lipid and cholesterol levels and increase the risk of blood coagulation.

• Intrauterine devices carry a higher-than-normal risk of pelvic inflammatory disease, since diabetic women have more difficulty fighting infections (Pillitteri, 2013).

Risk of contraceptive failure brings with it the risk of serious maternal and fetal complications. Therefore, in the diabetic woman, contraceptives with a high degree of effectiveness, such as Depo- Provera, Norplant, or subcutaneous implanted progesterone, are viable options (ADA, 2002a; Pillitteri, 2013).

Preconception Assessment

As previously discussed, unplanned pregnancies occur in approximately 67% of women with diabetes. Since major congenital malformations remain the leading cause of mortality and morbidity in infants of mothers with type 1 or type 2 diabetes, and elevated spontaneous abortion rates are also associated with © ALLEGRA Learning Solutions, LLC All Rights Reserved maternal hyperglycemia, diabetes care and education must begin before conception (ADA, 2002a; Buchanan, 2016). The most important objective during preconception is normoglycemia (Dunne, 1999). Education is the key to helping patients achieve normal serum glucose levels.

When the pregestational diabetic woman is considering pregnancy, the healthcare provider must evaluate several aspects of the woman’s lifestyle, including the following (ADA, 2002a; Buchanan, 2016; Mattson & Smith, 2015; Pillitteri, 2013):

• Classification of diabetes in pregnancy (see White’s classifications, below)

• Blood glucose levels

• Glycosylated hemoglobin (Hgb A1c) levels, a measure of the average blood glucose levels during the previous 60 to 90 days

• Frequency of self-monitoring blood glucose (SMBG)

• Presence and history of infections

• Presence and extent of cardiovascular, renal, and retinal damage (especially if the woman has had diabetes for more than 5 years)

• Appropriateness and adequacy of diet:

• Total caloric intake should be approximately 30 to 35 kcal/kg of ideal body weight

• Dietary composition should be approximately 40% to 55% carbohydrates, 20% to 25% protein, and 25% to 30% fat with less than 10% saturated fat

• Current insulin regimen

• Current exercise pattern

• Current family planning methods

• Current understanding of self-care responsibilities

• Current support system

Pregnant women with diabetes are categorized according to the White system.

Modified White’s Classification of Diabetes in Pregnancy Class Age of Duration Vascular Disease Treatment Onset Gestational Diabetes (GDM) A Any Any None Diet alone (Glucose Tolerance Test [GTT] only slightly abnormal) A1 During < 10 years None Diet alone pregnancy A2 During None Insulin pregnancy Pregestational Diabetes B Age 20 or <10 years None Insulin older C Ages 10–19 10–19 years None or minimal Insulin years D Before 10 >20 years Benign Insulin years of age (hypertension, retinopathy) E Calcified vessels of Insulin legs on x-ray (not done because of teratogenic effects of x-ray) F Any Any Nephropathy Insulin R Any Any Proliferative Insulin retinopathy H Any Any Cardiac disease Insulin T Any Any Kidney transplants Insulin (Adapted from Keely & Barbour, 2016; Mattson & Smith, 2015; Pillitteri, 2013)

To achieve her goal of a healthy pregnancy and newborn, the diabetic woman must become an active, participating member of her healthcare team. During her initial healthcare visit, a complete physical examination and laboratory evaluation should take place.

Elements to be assessed should include the following (American Diabetes Association, 2002b):

• Vital signs (especially blood pressure) • Dilated retinal exam by ophthalmologist or eye specialist with knowledge about diabetic eye disease • Cardiovascular examination • Neurological exam • Hgb A1c test • Serum creatinine

• Urinary excretion of total protein and/or albumin (levels over 190 mg/24 hours are at increased risk for pregnancy-induced hypertension; levels greater than 400 mg/24 hours increase the fetus’ risk for intrauterine growth retardation). • Although there is no treatment for these results, women should be counseled about their risks. • Individuals on angiotensin-converting enzyme (ACE) inhibitors should wait until their drug therapy is completed before undergoing this assessment. • Serum thyroid stimulating hormone and/or free thyroxine levels (especially in women with type 1 diabetes since they have a 5% to 10% incidence of hyper- or hypothyroidism) • Other tests as indicated by the results of the physical exam or laboratory evaluation

For the preconception management and education of a woman with diabetes, the healthcare professional should also do the following (ADA, 2002a):

1. Provide counseling about the risk and prevention of congenital anomalies, fetal and maternal complications of pregnancy, and the obstetrical risks associated with the disease.

2. Provide counseling about effective contraception until the woman’s blood glucose is well controlled.

3. Appropriately select antihyperglycemia therapy. Insulin is the best option for type 1 and type 2 patients, since the safety of oral antidiabetic agents is not guaranteed during pregnancy.

4. Set self-monitored blood glucose goals. These should include before- and after-meal blood glucose goals and Hgb A1c goals.

Blood Glucose Goals Before Meals 2 Hours after Meals Capillary whole-blood glucose 70–100 mg/dL < 140 mg/dL Capillary plasma glucose 80–110 mg/dL < 155 mg/dL

The glycosylated hemoglobin (Hgb A1c) value should be tested at regular intervals and will vary slightly between laboratories. The goal is to keep the Hgb A1c below 7%. The following table reflects how the Hgb A1c is related to the blood glucose level (ADA, 1996):

11 270 12 300 13 330

Prenatal Assessment

During the prenatal period, the pregnant woman should be assessed for all of the abovementioned items as well as the following (Mattson & Smith, 2015):

• Number of episodes of maternal hypoglycemia or hyperglycemia

• Presence of ketonuria

• Urinalysis and urine culture if symptoms are present

• Fetal status via ultrasound, maternal serum alpha-fetoprotein (AFP), biophysical profile (BPP), nonstress testing (NST), contraction stress testing (CST), fetal movement, amniocentesis for lung maturity, and Doppler studies of umbilical vein and arteries

In addition, the pregestational mother should be evaluated for her ability to adapt to her current illness. The healthcare provider must assess the adequacy and ability of her support system, the presence and adequacy of her coping skills, her financial status, her occupation and employment status, her family’s response to the pregnancy, whether this is a planned or unplanned pregnancy, her feelings about the pregnancy and its high-risk status, and the availability of appropriately trained medical and healthcare facilities and personnel to care for her and her baby (Mattson & Smith, 2015).

GESTATIONAL DIABETES MELLITUS (GDM)

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance first recognized during pregnancy. The definition applies whether insulin or diet modification is used for treatment and whether or not the condition persists after pregnancy. Affecting approximately 4% to 8% of all pregnancies in the United States and millions of women worldwide, it can result in serious maternal and fetal complications (ADA, 2002b; Padayachee & Coombes, 2015).

Risk Factors for GDM

Risk factors associated with the development of GDM in any pregnancy include the following (American College of Obstetrics and Gynecology [ACOG], 2005; ACOG, 2013; Keely & Barbour, 2016; Mattson & Smith, 2015; Pillitteri, 2013):

• Maternal obesity (weight greater than 20% above the ideal) • Age over 25 years • Hypertension • Multiparity • Ethnic background—African American, Chinese, Hispanic, Saudi Arabian, Native American (particularly Navajo) • Early diagnosis of GDM during a previous pregnancy • The need for insulin during a previous pregnancy • History of large babies (greater than 9 pounds or 4,000 grams) • History of unexplained intrauterine fetal demise (IUFD) or neonatal death • History of congenital anomalies in previous pregnancy • History of polyhydramnios in previous pregnancy • Polycystic ovarian disease (PCOS) • Family history of diabetes (one close relative, such as a parent or sibling, or two distant ones)

Risk factors in a current pregnancy associated with GDM include the following (Mattson & Smith, 2015):

• Development of polyhydramnios • Increased fundal height relative to dating of pregnancy • Persistent glycosuria on at least two successive prenatal visits • Proteinuria • Increased urinary frequency after the first trimester • Recurrent candida infections • Reported feelings or behaviors of excessive thirst or hunger

Estimates show GDM recurring in a substantial number of subsequent pregnancies after a pregnancy with GDM. Thus, it is important for healthcare providers to counsel women with GDM about their risk of recurrence and the importance of appropriate prenatal screening and care. This allows for earlier detection of the disease and improved management and outcomes.

GDM Screening

While GDM has been recognized for decades, controversy surrounds its clinical significance and how it should be detected. This is because the selective screening of women based on their obstetrical history or clinical symptoms has not been effective in determining which women will develop GDM. In addition, 50% of women with GDM have no risk factors (Mattson & Smith, 2015).

The American Diabetes Association (ADA) recommends universal screening on all pregnant women. The American College of Obstetricians and Gynecologists (ACOG) recommends screening all pregnant women aged 30 years and older and any woman younger than 30 years who has any identified risk factors.

According to ACOG, a woman is considered at a low risk for developing GDM (and thus may not need laboratory screening) if she meets all of the following characteristics (ACOG, 2013; ADA, 2002b):

• Age less than 25 years • Not a member of an ethnic group with high GDM prevalence (Hispanic, African, Native American, South or East Asian or Pacific Islands ancestry) • Body mass index  25 • No known diabetes in first-degree relatives • No history of abnormal glucose tolerance • No history of poor obstetric outcome

Women at average risk for GDM should be screened initially at 24 to 28 weeks’ gestation (ADA, 2002b; CDC, 2017).

If a woman has been identified with glucose intolerance prior to 24 weeks of gestation, she should undergo a glucose screening test (GST) using a 50-gram, 1-hour test (described later in this section).

The following criteria confirm a diagnosis of diabetes (ADA, 2002b; CDC, 2017; Simpson & Creehan, 2013). Either criterion must be confirmed on a subsequent day:

• A fasting plasma glucose level > 126 mg/dL (7.0 mmol/l), or • A casual plasma glucose > 200 mg/dL (11.1 mmol/l).

If the woman has a serum glucose greater than that listed above, or if she has average- or high-risk characteristics, she can be screened for GDM using one of two approaches.

1. The one-step approach involves a diagnostic oral glucose tolerance test (OGTT), which is performed without a prior plasma or serum glucose screening.

• This cost-effective approach is often used in high-risk patients, such as some Native American groups (ADA, 2002b; Pillitteri, 2013; Setji, Brown, & Feinglos, 2005). © ALLEGRA Learning Solutions, LLC All Rights Reserved

2. The two-step approach involves an initial screening test called a glucose challenge (screening) test, or GST.

• It measures the plasma or serum glucose concentration 1 hour after the ingestion of 50 grams of oral glucose.

• Those women who exceed the recommended glucose threshold proceed to complete a diagnostic OGTT.

• When a glucose threshold value > 140 mg/dL is used, 80% of the women with GDM are identified.

• When a glucose threshold value >130 mg/dL is used, 90% to 100% of women with GDM are identified (ADA, 2002b; Setji, Brown, & Feinglos, 2005; Troiano, Harvey, & Chez, 2013).

The diagnostic OGTT involves the administration of either 75 grams or 100 grams of oral glucose. The 75-gram glucose load and the threshold values listed below have not been as well validated for detecting at-risk infants or mothers as the 100-gram OGTT. If the 75-gram, 2-hour glucose tolerance test is used, the following values are seen as diagnostic of GDM (ADA, 2002b; Simpson & Creehan, 2013):

Milligrams per deciliter (Millimols per liter) (Mg/dL) Mmol/l Fasting 95 5.3 1-hour 180 10.0 2-hour 155 8.6

If the 100-gram test is used, a definite diagnosis of GDM requires that two or more of the venous plasma (or serum) glucose concentrations meet or exceed the following values (ADA, 2002b; Simpson & Creehan, 2013):

Milligrams per deciliter (Millimols per liter) (Mg/dL) Mmol/l Fasting 95 5.3 1-hour 180 10.0 2-hour 155 8.6 3-hour 140 7.8

According to the ADA (2002b), “The test should be done in the morning after an overnight fast of between 8 and 14 hours and after at least three days of unrestricted diet and unlimited physical activity. The woman should remain seated and should not smoke throughout the test” (p. S950).

The woman is retested at 32 weeks if only one value is elevated or if she has any risk factors for GDM.

GENERAL MANAGEMENT FOR DIABETES IN PREGNANCY

Therapeutic strategies for women with GDM include the following (ADA, 2002b):

• Daily self-monitoring of blood glucose levels

• Increased surveillance of pregnancies at risk for fetal demise (especially when the pregnancy is past term)

• Urine ketone monitoring

• Assessment of fetal growth by ultrasonography (especially in the third trimester)

Women with GDM can control their glucose levels with diet and exercise and, in some cases, with insulin.

Nutrition Therapy

Proper nutrition plays a key role in any pregnancy but it is especially important for the woman who is pregnant and diabetic. Diet management is the cornerstone of diabetes management (Keely & Barbour, 2016; Setji, Brown, & Feinglos, 2005; Troiano, Harvey, & Chez, 2013).

For many women, eating a well-balanced diet is enough to keep their blood sugar within a normal range and provide the appropriate nutrients for their baby, but some women will need to inject insulin as part of the management of this disease. All pregnant women with diabetes will need to closely monitor their blood glucose levels and follow a meal plan to ensure that both they and their growing baby receive adequate nutrients for health (Keely & Barbour, 2016).

Helping the pregnant woman with diabetes reach her nutritional goals can best be achieved through the coordinated efforts of a team of healthcare practitioners such as a

There is no one GDM diet at the present time. There is no evidence for or against moderate caloric restriction in obese women with GDM. If nutritional therapy for obese women with GDM includes calorie restriction, ACOG recommends that the diet be restricted by no more than 33% of her total caloric intake (Setji, Brown, & Feinglos, 2005).

The ADA states that a 35% to 40% restriction of calories has been shown to decrease maternal glucose levels and improve maternal and fetal outcomes (ADA, 2002b).

Caloric intake recommendations are often based on prepregnancy body weight. The following guidelines are suggested for those women with diabetes during pregnancy but every woman must collaborate with her healthcare provider to determine the proper intake given her clinical condition (Troiano, Harvey, & Chez, 2013):

• 35 to 40 kcal/kg per day for women who are within 80% of their ideal body weight

• 30 kcal/kg per day for women who are within 80% to 120% of their ideal body weight

• 24 kcal/kg per day for women who are within 120% to 150% of their ideal body weight

• 12 to 15 kcal/kg per day for women who are greater than 150% of their ideal body weight

According to current dietary guidelines, dietary protein should not exceed 10% to 25% of total daily calories, and the remaining 75% to 90% of calories should be distributed between carbohydrates and fats. Alcohol consumption should be undertaken in moderation since it can result in hypoglycemia or hyperglycemia. Micronutrient supplementation (vitamins and minerals) is not considered necessary if the woman’s diet is adequate. Interestingly, higher intakes of animal protein (especially red meat) are associated with a greater risk of diabetes in pregnancy while diets high in vegetable protein are associated with a lower risk of gestational diabetes (Bao et al., 2013).

Since nutritional needs change during pregnancy, the best way to determine what is appropriate for the mother and her fetus is to follow the recommendations of her healthcare team. At a minimum, dietary recommendations should be evaluated prior to conception, as well as during each trimester. Weight gain or loss should be monitored carefully and the diet and insulin therapy adjusted as needed.

A weight gain of 25 to 32 pounds is considered appropriate for pregnancy. For those women who are overweight at the time of their pregnancy, weight gain should probably not exceed 15 pounds.

Exercise

Since diabetes and obesity have been called the “epidemic of the 90s,” and the issue of obesity and diabetes has continued into the 21st century, the need for Americans to “get moving” has never been greater. While many people have great difficulty starting (and maintaining) an exercise program, regular physical activity is one of the cornerstones of diabetic management, especially for those women with pregestational diabetes and GDM (Artal, Catanzaro, Gavard, Mostello, & Friganza, 2007; Keely & Barbour, 2016; Flood & Constance, 2002; Padayachee & Coombes, 2015; Setji, Brown, & Feinglos, 2005). However, other studies have shown that, in healthy pregnant women with normal body mass indexes, exercise during the second half of pregnancy does not prevent gestational diabetes or improve insulin resistance (Stafne et al., 2012).

A contracting skeletal muscle increases its glucose uptake by 35 times. Following exercise, glucose tolerance is increased for various amounts of time depending on insulin availability and the amount of contractile activity. Muscles help regulate the capacity for the contraction-stimulated glucose transport (Padayachee & Coombes, 2015).

Regular exercise improves blood glucose levels, decreasing the need for insulin or oral diabetic medication (Flood & Constance, 2002; Setji, Brown, & Feinglos, 2005). It can also lead to weight reduction, mood improvements, and increased social interaction.

Prescribing an exercise regimen for pregnant women requires an appropriate level of knowledge about the unique aspects of the pregnant woman’s physical capacity, anatomy, and physical changes that accompany pregnancy (Keely & Barbour, 2016). For example, pregnant women who have diabetes are at a higher risk for injuries during exercise, often because many of them have muscle atrophy from sedentary lifestyles (Artal et al., 2007; Padayachee & Coombes, 2015;).

Therefore, prior to recommending an exercise routine for the pregnant woman with diabetes, the healthcare professional should complete a thorough assessment of the individual for macrovascular, microvascular, cardiovascular, and neuropathic complications. Such an assessment can help ensure a safe regimen and optimal maternal and fetal outcomes, and might include the following (Flood & Constance, 2002):

• A graded exercise stress test • Blood pressure screening • Serum lipid profile analysis

• Resting and exertional heart rate • Evaluation for intermittent claudication during physical activity • Assessment of the presence of leg pain during rest or sleep • The presence of paresthesias or altered sensations • A history of smoking • Skin assessment, paying special attention to the areas between the toes and metatarsal heads (since neuropathy can decrease sensation and the ability of the person to detect injuries) • Use of the Semmes-Weinstein monofilament test to assess protective sensation on the foot • An annual dilated eye exam

Once the results of these tests are evaluated, individuals can be appropriately advised about their exercise program.

• A goal of 30 minutes a day for most days of the week is desirable.

• However, those who are just beginning an exercise program should strive to divide that activity into two 15-minute or three 10-minute sessions daily.

• If the individual has been completely inactive for an extended period of time, shorter exercise sessions may be necessary when a regimen is first started (Flood & Constance, 2002).

Exercise should be performed at an intensity that allows the individual to breathe and talk at the same time. Exercise intensity can be gauged by determining the desired heart rate and checking the pulse to see if, during exercise, the heart rate falls within this range.

The standard formula for estimating the desired heart range is to subtract the individual’s age from 220. This is the maximum number of times your heart should beat per minute during exercise (Mayo, 2018)

This formula is not appropriate for everyone. Those individuals on beta blockers or those with pacemakers, arrhythmias, or autonomic neuropathies should consult their physicians before using this formula (Flood & Constance, 2002).

Recommended exercises for the pregnant diabetic include brisk walking, biking, swimming, and prenatal stretching exercises. Jogging, tennis, racquetball, volleyball, and water skiing are generally not recommended during pregnancy due to the jarring motions that occur during these activities (Setji, Brown, & Feinglos, 2005).

Individuals with diabetes who undergo an exercise regimen must also be careful to (Flood & Constance, 2002)

• avoid hypoglycemia, • avoid hyperglycemia (more common in type 1 diabetics),

• avoid high-intensity exercise (which may actually elevate glucose levels), and • keep their feet healthy (since minor injuries can result in amputation).

Medication Therapy

Insulin therapy is considered when diet and exercise therapy are not effective in reducing glucose to desirable levels (Setji, Brown, & Feinglos, 2005). Insulin therapy optimizes glycemic control and enhances the woman’s quality of life.

The decision to utilize insulin therapy can be made based on maternal glucose levels with or without the assessment of fetal growth characteristics. According to the ADA (2002b), insulin therapy is recommended when medical nutrition therapy (MNT) fails to maintain maternal glucose levels at the following levels:

Fasting whole blood glucose ≤ 95 mg/dl ≤ 5.3 mmol/l Fasting plasma glucose ≤ 105 mg/dl ≤ 5.8 mmol/l 1-hour postprandial whole blood glucose ≤ 140 mg/dl ≤ 7.8 mmol/l 1-hour postprandial plasma glucose ≤ 155 mg/dl ≤ 8.6 mmol/l 2-hour postprandial whole blood glucose ≤ 120 mg/dl ≤ 6.7 mmol/l 2-hour postprandial plasma glucose ≤ 130 mg/dl ≤ 7.2 mmol/l

Both the woman with diabetes and the woman with gestational diabetes may need insulin. Since oral hypoglycemic agents (OHAs) are not regularly utilized for the pregnant diabetic patient (they cross the placenta and are potentially teratogenic), human insulin is often the drug of choice during pregnancy and during the reproductive years to ensure that anti-insulin antibodies do not cross the placenta and contribute to fetal macrosomia. The dosage and type of insulin are based on the individual woman’s clinical situation. They are also based on the woman’s level of self-management skills. It is important to match the medication therapy to the physiology of the woman’s disease.

Self-monitored blood glucose levels should serve as the guide for the dose and the timing of insulin administration. Most pregnant women can adequately control their blood glucose levels with one to two injections per day of a mixed dose of intermediate- acting insulin (NPH or lente) and a short-acting insulin (regular) (Simpson & Creehan, 2013).

Extensive education about the self-administration of medication must accompany the successful initiation of insulin therapy. This education can usually begin on an outpatient basis. Components of a successful education program include the following (Simpson & Creehan, 2013):

• Information about the types of insulin, their duration of action, their peak of action

• The importance of timing meals and snacks to avoid hypoglycemia

• Information on how to check insulin bottles for expiration dates and what to look for if the medication is expired or inappropriate for use (clumping, frosting, precipitate, or color/clarity changes)

• Information on medication storage (should be in a refrigerator and open bottles should be used within 30 days) and administration (to avoid the production of bubbles within the bottle, the medication should be rolled between the hands and never shaken)

In addition, patients should be thoroughly instructed on how to select injection sites, administer the medication, and dispose of medication and needles:

• Absorption is most rapid and most consistent from medication injected into the abdomen, followed by the arms, thighs, and buttocks; however, arms and legs should not be used on the day they are going to be exercised.

• Proper hand washing should be emphasized.

• Proper skin preparation should be emphasized, including the use of alcohol on the site prior to injection to cleanse the site.

• A pen device can be used for individuals who are fearful of needles.

• A 100-unit syringe is recommended since it is easier to read than the 50-unit or 30-unit syringe.

• Aspiration at the site is not necessary.

• The site should not be massaged after the medication is injected.

• The medication and needles should be disposed of properly.

Once the education session is complete, the healthcare professional should follow up with the woman 2 days after the initial session to determine if the she correctly understood the information and has been successfully administering the medication. After that, the woman can be followed up every 2 weeks or so to determine if the doses need to be adjusted, if any reactions have occurred, or if she has any further questions or concerns (Simpson & Creehan, 2013).

QUESTIONS FOR REFLECTION

What are the various methods of managing gestational diabetes?

What role does the healthcare provider play in these methods in the overall care of the patient with gestational diabetes?

ADDITIONAL MANAGEMENT ISSUES

Additional interventions that can influence the outcome of the disease and the pregnancy are numerous and focus on issues related to

1. metabolism of carbohydrates, proteins, fats, and electrolytes; 2. anxiety related to the disease and the outcome of the neonate; 3. risk of maternal and fetal injury; and 4. changes in the family systems because of the demands of the disease and the care required to effectively manage it (Mattson & Smith, 2015).

The effective management of carbohydrate, protein, fat, and electrolyte metabolism requires close supervision prior to the pregnancy and during the pregnancy.

• Blood glucose levels should be monitored and recorded at least four times each day (before and after each meal and at bedtime).

• In addition to the disease process, abnormal glucose levels may be caused by the user performing the technique improperly, anemia (which may falsely elevate the glucose levels), or erythema (which may falsely lower the results) (Mattson & Smith, 2015).

As her glucose levels change during the pregnancy, a woman’s insulin needs may also change. She may need to switch to a different form of insulin, increase the number of injections needed on a daily basis, or she may require pump therapy (Mattson & Smith, 2015).

In addition, the woman needs to test her urine on a regular basis to determine the presence of ketones. This is usually done on her first morning urine specimen, but it is also recommended when her glucose control undergoes any changes, when her blood glucose levels are above 200 mg/dL, or during any illness. Persistent ketonuria is one sign that she may need to eat an additional snack or make appropriate changes in her insulin regimen (Mattson & Smith, 2015). © ALLEGRA Learning Solutions, LLC All Rights Reserved

Patients with diabetes during pregnancy should be assessed to determine their level of understanding about hypoglycemia and its signs and symptoms. Symptoms of mild hypoglycemia include the following (Mattson & Smith, 2015):

• Tremors • Tachycardia • Diaphoresis • Paresthesia • Excessive hunger • Pallor • Shakiness

Moderate hypoglycemia will present with the following symptoms (Mattson & Smith, 2015):

• Headache • Mood change • Irritability • Inability to concentrate • Drowsiness • Confusion • Impaired judgment • Slurred speech • Staggering gait • Double or blurred vision

Severe hypoglycemia is characterized by disorientation, unconsciousness, and/or seizures (Mattson & Smith, 2015).

Women with diabetes during pregnancy or those who tend to get hypoglycemic should be instructed to have a source of fast-acting carbohydrate with them at all times. Examples of this form of carbohydrate are six to eight Lifesavers, 4 ounces (120 ml) of fruit juice, or 2 tablespoons of raisins (Mattson & Smith, 2015).

In addition to assessing the woman’s clinical status and physiological state, the healthcare provider should also evaluate the woman’s understanding of the impact of her disease on her health and that of her baby (Mattson & Smith, 2015):

• Does she understand the importance of blood glucose control on her long- term health?

• Does she understand the importance of blood glucose control on the health of her unborn baby?

• Does she understand the various antenatal tests that may be performed on her to assess the well-being of her baby?

• Is she able to participate in decision making and planning about her medical and obstetrical care during the pregnancy?

• Is she able to effectively verbalize any fears or concerns about any aspect of her care or the care of her baby?

• Does she have a supportive significant other and/or family?

• Is her significant other and/or family able to assist her in her self-care behaviors and practices during the pregnancy?

If the answer to any of the above questions is “no,” the healthcare provider must evaluate the woman’s level of understanding and abilities regarding the particular issue(s) and provide appropriate education in that area.

Education about the disease and the intentional and immediate correction of even slight hyperglycemia with rapid-acting insulin has been shown to improve fetal outcomes and reduce the rates of fetal malformation (Howorka et al., 2001).

Tests for Fetal Placental Function and Fetal Well-being

The fetus of a diabetic pregnancy must be monitored carefully and assessed according to the specific clinical condition of the mother. The following antenatal tests may be completed (Simpson & Creehan, 2013; Pillitteri, 2013):

• Alpha-fetoprotein (AFP) at 15 to 17 weeks (because of the association with higher-than-normal incidence of birth anomalies such as neural tube defects)

• Ultrasound at 18 to 20 weeks (to detect gross abnormalities), repeated at 28 weeks (for assessment of fetal growth, amniotic fluid volume, placental location, and biparietal diameter), and then repeated as necessary at 36 to 38 weeks of gestation

• Creatinine clearance test each trimester (for assessment of the vascular system and uterine perfusion)

• Nonstress test (NST) done weekly to assess placental functioning and fetal status

• Biophysical profile (BPP) done weekly to assess placental functioning and fetal status

• Fetal movement assessment (considered reactive if the fetus moves 10 times in a 2-hour period)

• Lecithin-sphingomyelin (L/S) ratio by amniocentesis by week 36 to assess fetal lung maturity and the presence of lung surfactant. While corticosteroids may be given safely and with excellent results in nondiabetic mothers to facilitate fetal lung maturity, they are not usually administered to diabetic mothers with poor glucose control since they may impair fetal insulin release and fetal islet cell development.

Serum Glucose Monitoring

Almost all women with diabetes can be taught to monitor their serum glucose for hyperglycemia or hypoglycemia. While the woman with preexisting diabetes may be accustomed to performing this simple test on a daily basis, the woman with gestational diabetes may need to assess her serum glucose only on a weekly basis.

Ideally, the finger prick technique is used along with a glucose meter with digital readout (versus the test strip with a color-coded chart). The woman should be instructed that a fasting plasma glucose level below 100 mg/dL and a 2-hour postprandial level below 120 mg/dL are considered normal (Pillitteri, 2013).

If the woman discovers she is hypoglycemic, she should be instructed to eat some form of sustained carbohydrate such as milk or crackers. The ingestion of a complex carbohydrate can help prevent a rebound hypoglycemia, which can be even more severe than the original episode.

If the woman discovers she is hyperglycemic, she should assess her urine for acetone (ketones). If she finds acetone on more than two occasions, she should be instructed to contact her healthcare provider. Excess acetone can contribute to maternal diabetic ketoacidosis and fetal anoxia. The second and third months of pregnancy are the most frequent times for insulin coma. The sixth month of pregnancy (when insulin resistance is highest) is the most common time for a diabetic coma (Pillitteri, 2013).

Timing for Birth

Prior to the relatively recent era of maximum control during pregnancy, women with diabetes were carefully monitored for the timing of birth. The most crucial time for a positive fetal outcome was between 36 and 40 weeks, when the fetus is utilizing large maternal stores for its growth. Since fetal loss secondary to placental insufficiency was common during this time, many pregnancies were terminated prior to 36 weeks. Attempts were made to keep the fetus from being delivered too prematurely, as this posed further complications (Dunne, 1999; Pillitteri, 2013).

For many years, babies were delivered by cesarean section at approximately 37 weeks because they were large and vaginal deliveries were difficult. In addition, cesarean section was chosen since, at 37 weeks, the cervix was not yet ripe or responsive to contractions. Furthermore, in diabetic pregnancies, the placenta sometimes did not function sufficiently and fetal distress resulted (Pillitteri, 2013).

There are no current data to support a cesarean delivery primarily on the basis of GDM even though there is a higher risk of shoulder dystocia and macrosomia in women with GDM (ADA, 2002b; Setji, Brown, & Feinglos, 2005).

If the fetal weight is estimated to be greater than 4,000 grams, cesarean delivery may be considered (Setji, Brown, & Feinglos, 2005).

At the present time, antepartum testing of fetal status is much more sophisticated and pregnancies can be well maintained within safe limits by monitoring the fetus with nonstress tests and other antenatal tests. Thus, the last weeks of pregnancy do not carry with them the same risks they once did. Vaginal births with positive fetal outcomes are viable options, since surgical (cesarean) births always carry higher risks than vaginal births. Labor can be induced and the cervix ripened, both the fetus and the mother can be closely monitored during labor, and glucose levels during labor can be regulated carefully (Pillitteri, 2013).

Intrapartum Management of the Diabetic Woman

The condition of the fetus and the diabetic mother is the primary concern during the intrapartum period. The maternal history must be thorough and must include information about overall glucose control; the presence of any vascular complications; the number of episodes of hypoglycemia, hyperglycemia, or ketoacidosis; the current diabetic regimen; the time of the last meal; and the last insulin injection. The woman should not receive anything by mouth during this period, her glucose level should be obtained and documented, and intravenous access should be established (Simpson & Creehan, 2013).

In addition to the suggestions above, the following guidelines are suggested (Keely & Barbour, 2016; Simpson & Creehan, 2013):

• Blood glucose should be checked on admission and then every 1 to 2 hours during the intrapartum period.

• When blood glucose levels reach 120 mg/dL, intravenous regular insulin should be administered via a controlled infusion device piggybacked into a primary line.

• If the woman’s blood glucose level was well controlled antenatally, she may not need insulin during labor.

• The primary intravenous infusion should be 0.9% sodium chloride with a glucose-containing solution as the secondary line.

• The infusion rate should be based on the blood glucose values and titrated according to the individual institution’s algorithm when the blood glucose levels exceed 110 mg/dL.

• While insulin doses may vary, the general recommendation is that insulin should be administered at 1 U/hr for blood glucose values of 100 to 140 mg/dL; 1.5 U/hr for blood glucose values of 141 to 180 mg/dL; 2.0 U/hr for glucose values of 181 to 200 mg/dL; and 2.5 U/hr for blood glucose levels greater than 220 mg/dL.

• The prenatal record should be thoroughly reviewed for any pertinent history.

• Laboratory studies that might be ordered include the Hgb A1c and ultrasound.

• The fetus should be monitored continuously.

• The woman should be encouraged to labor on her left lateral recumbent position to improve uterine perfusion and fetal oxygenation.

• Neonatal resuscitative supplies and trained personnel should be immediately available in the event that the newborn has respiratory distress.

• If the woman is electively induced, cervical ripening may be indicated. If oxytocin is administered for an induction, the medication must be administered in a separate solution and infusion device from the insulin administration set.

Management during the Postpartum Period

During the postpartum period, the woman with diabetes may have to undergo insulin regulation (Keely & Barbour, 2016). Since the placental hormones that contributed to insulin resistance are gone, the reason for her insulin resistance is gone and the woman may not need any insulin during the immediate postpartum period.

• Oral intake should be initiated as soon as possible.

• Several days later, she may return to her prepregnant insulin requirements. One- and two-hour postprandial blood glucose tests should be obtained and the woman’s glucose regulated accordingly (Pillitteri, 2013).

• The woman with gestational diabetes will usually exhibit normal glucose values by approximately 24 hours after birth and will usually need no further medication or diet therapy.

Breastfeeding is allowed and encouraged, since insulin does not pass into breast milk (ADA, 2002b). However, the woman must be alert to signs of hypoglycemia and so may wish to eat a snack prior to breastfeeding to prevent hypoglycemia (Dunne, 1999; Pillitteri, 2013; Simpson & Creehan, 2013).

The woman who has hydramnios is at risk for postpartum hemorrhage secondary to poor uterine contractibility; as a result, she must be carefully observed and assessed during this time (Dunne, 1999; Pillitteri, 2013; Simpson & Creehan, 2013).

The incidence of puerperal infection is higher in diabetic women, so the healthcare provider must be alert to signs and symptoms of infection (Simpson & Creehan, 2013).

Contraception should be discussed before the patient is discharged and again at the 6- week postpartum appointment (Dunne, 1999; Simpson & Creehan, 2013).

NEW THERAPIES FOR THE PREGNANT WOMAN WITH DIABETES

Exciting new therapies are available for the pregnant woman with diabetes. This section will focus on the use of oral hypoglycemic agents, new forms of insulin, insulin pump therapy, and islet cell transplantation.

Oral Hypoglycemic Agents (OHAs)

OHAs were once used during pregnancy but their use today remains controversial since they have been linked to neonatal hypoglycemia, macrosomia, and anomalies.

• The studies on their use have been limited since women with type 2 diabetes are often hyperglycemic or hyperinsulinemic in their first trimester, and both conditions are risk factors for fetal anomalies.

• Since OHAs cross the placenta by passive diffusion, their effect can vary substantially, even among similar OHAs, and it is this difference that determines their risk and benefit in pregnancy.

• However, one randomized, unblinded clinical study compared perinatal outcomes in GDM patients where insulin and glyburide were used. All of the patients were past their first trimester of pregnancy and all showed similar outcomes (ADA, 2002b).

The most recent data suggests that OHAs may be used safely in the second trimester when organogenesis is complete (El-Sayed & Lyell, 2001). Metformin has been associated with a slight increase in preterm birth and the need for supplemental insulin (Keely & Barbour, 2016).

The main classifications of OHAs include the following (El-Sayed & Lyell, 2001):

1. Sulfonylureas (chlorpropamide, glyburide, glipizide), which act by stimulating pancreatic insulin secretion

2. Biguanides (metformin), which enhance hepatic insulin action

Glyburide is commonly known by the trade names DiaBeta (Canada only), Euglucon, Glynase PresTab, and Micronase. The following table provides a summary of key information about this medication (Skidmore-Roth, 2018). Glyburide is not FDA approved for use in pregnancy because it crosses the placenta (Keely & Barbour, 2016). The healthcare provider is cautioned that the information in this table is not exhaustive or comprehensive and complete information on this medication must be obtained prior to administering it to the patient.

Actions Adult Oral Dosage Side Effects and/or Contraindications and Routes Adverse Reactions and/or Precautions • Causes • DiaBeta/Micronase • Headache • Hypersensitivity functioning 2.5–5 mg initially, • Weakness • Pregnancy beta cells in then increased to • Heartburn • Juvenile or brittle pancreas to desired response • Blurred vision diabetes release insulin • Glynase PresTab: • Fatigue • Elderly • May increase 1.5–3 mg/day • Nausea • Cardiac disease number of initially and may • Vomiting • Renal disease available increase by 1.5 • Diarrhea • Thyroid disease insulin mg/week © ALLEGRA Learning Solutions, LLC All Rights Reserved

receptors • Hepatotoxicity • May reduce • Cholestatic basal hepatic jaundice glucose • Hypoglycemia secretion • Leukopenia • Not effective if • Thrombocytopenia patient lacks • Aplastic anemia functioning beta cells

Metformin hydrochloride decreases both fasting and postprandial blood sugars in diabetics, yet has no effect on nondiabetics. The following table provides a summary of key information about metformin, which may be more commonly known by its trade names Glucophage or Glucovance (Skidmore-Roth, 2018).

The healthcare provider is cautioned that the information in this table is not exhaustive or comprehensive, and complete information on this medication must be obtained prior to administering it to the patient.

Actions Dosage and Routes Side Effects and/or Contraindications Adverse Reactions and/or Precautions • Inhibits • PO: 500 mg bid • Headache • Hypersensitivity hepatic initially, then increase • Weakness • Hepatic or renal glucose to desired response • Dizziness disease production • Adjust dosage q 2–3 • Drowsiness • Alcoholism • Increases weeks or 850 mg • Nausea • Cardiopulmonary sensitivity every day with • Vomiting disease of morning meal, with • Diarrhea • History of lactic peripheral dosage increased • Thrombocytopenia acidosis tissue to every other week to a • Rash • Pregnancy insulin maximum of 2,250 • Lactic acidosis • Elderly mg/day • Hypoglycemia • CHR

New Forms of Insulin

Lispro insulin (Humalog) is a recombinant insulin that is rapidly absorbed and reaches its peak action within 1 hour of injection. Patients who use Lispro do not have to wait long for meals and they experience fewer incidences of late hypoglycemia, so their glucose control is improved. Its use in pregnancy is controversial. Lispro, like insulin, does not cross the placenta (El-Sayed & Lyell, 2001).

Insulin Pump Therapy

A continuous insulin pump is an excellent way for the diabetic pregnant woman to maintain her diet, balance her exercise level, and maintain a safe serum glucose level, especially if multiple insulin injections have failed to maintain glycemic control (El-Sayed & Lyell, 2001; Pillitteri, 2013; Simpson & Creehan, 2013). The insulin pump maintains a more physiologic insulin administration than multiple-dose insulin injections since it can

The insulin pump is an automatic pump about the size of a transistor radio. It contains a syringe of insulin and a thin polyethylene tube leading to a small-gauge needle that is planted in the subcutaneous tissue of the woman’s abdomen. It delivers a continuous rate of 1 U per hour of insulin 24 hours a day. A bolus of insulin can be manually delivered by the woman before she eats a snack or a meal, based on the number of carbohydrates to be consumed. The pump insertion site must be cleaned daily and covered with sterile gauze and the site changed every 24 to 48 hours to ensure optimal absorption of the insulin (El-Sayed & Lyell, 2001; Pillitteri, 2013).

The advantages of the pump are numerous (American Diabetes Association, 2015b; El- Sayed & Lyell, 2001):

• It reduces blood glucose deviations. • It reduces the incidences of early morning hypoglycemia. • It reduces variations in insulin absorption. • It reduces postprandial hyperglycemia due to delayed gastric emptying (common during pregnancy). • It increases patient contact with the healthcare team and allows for closer monitoring of glucose levels. • It allows for more dietary flexibility. • It enhances the individual’s lifestyle. • It eliminates the need for individual insulin injections • It allows the individual to exercise without having to eat large amounts of carbohydrates.

Important disadvantages of the insulin pump include the following (American Diabetes Association, 2015b; El-Sayed & Lyell, 2001):

• It requires a very compliant patient. • Mechanical problems can result in hyperglycemia and ketoacidosis.

• Infection at the insertion site may result in deterioration of glucose control and impaired insulin absorption. • It is more expensive than multiple-dose injections. • It can cause weight gain • It can cause diabetic ketoacidosis (DKA) if the catheter comes out and insulin is not received.

The pump should not be allowed to get wet, so the pump and needle must be removed when the woman showers or swims. It should not remain disconnected for more than 1 hour. Blood glucose monitoring is still required four times a day (fasting and 1 hour after each meal) to assure that the pump delivers insulin at the prescribed rate. In addition, when the pump therapy is first initiated, the woman must awaken and perform a 2 a.m. blood glucose test since this is the time when she is most vulnerable to hypoglycemia (Pillitteri, 2013).

Although insulin pump therapy in pregnancy is still limited, studies have shown favorable maternal and fetal outcomes. However, healthcare professionals are encouraged to initiate this therapy during the preconception phase to allow for ideal glucose control (El-Sayed & Lyell, 2001). Ultimately, patient education is crucial to optimal glycemic control no matter what method is utilized (Howorka et al., 2001).

Insulin pens are another option for insulin management that are being used with some diabetics during pregnancy.

Islet Cell Transplantation

Islet cell transplantation involves transplanting the pancreas as part of a combined kidney-pancreas transplant. Since the islet cells comprise about 2% of the pancreas, transplantation of just the islet cells may be a more suitable alternative as this new field of medicine advances. This procedure is usually done in women with end-stage renal disease from diabetes. In women who have had islet cell transplantation, studies have shown successful pregnancy outcomes. However, complications have included a higher incidence of the following (El-Sayed & Lyell, 2001):

• Intrauterine growth restriction • Hypertension • Fetal distress • Cesarean section

SUMMARY

The impact of diabetes during pregnancy is evident in the abundance of clinical, pathophysiological, and epidemiologic data. Maternal and fetal complications can be severe and life-threatening. Screening plays an important role in the prompt recognition of the disease. The effective management of the pregnant diabetic can involve diet, exercise, and/or medication therapy. Patient education is also crucial in helping to assure a positive outcome for both mother and baby. New treatment options show great

© ALLEGRA Learning Solutions, LLC All Rights Reserved promise for the optimal control of blood glucose levels and include oral hypoglycemic agents, new forms of insulin, insulin pump therapy, and islet cell transplantation.

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