A Practical Guide to Insulin Pump Therapy for Pregnancy

Chapter 1

To what extent is diabetes a problem?

Worldwide, the number of people who have diabetes is rising. In the United States alone, between 1980 and 2006, the number of people less than forty-five years old who were known to have diabetes increased from 5.6 to 16.8 million. Although the frequency with which type 1 (formerly termed juvenile-onset or insulin-dependent) diabetes is being diagnosed has increased only modestly, recently, type 2 (formerly termed adult-onset or noninsulin-dependent) diabetes is being diagnosed much more frequently.

The distinction in terminology (i.e., type 1 or 2) is important for at least two reasons. First, if practitioners recognize the diabetes type, it focuses their attention on potential strategies for treating their patients. For example, insulin resistance is an important contributor to hyperglycemia (abnormally elevated blood glucose level) in people who are obese or have type 2 diabetes; therefore, treatments that reduce insulin resistance have the potential to play a significant role in their treatment. Typically, insulin resistance is not a major contributor to hyperglycemia in people who have type 1 diabetes or who are not obese (albeit racial differences influence this); therefore, treatments that are based primarily on reducing insulin resistance may not benefit them as much.

Second, recognizing the diabetes type is more accurate for descriptive and statistical purposes. For example, recently, type 2 diabetes has been diagnosed more frequently in children and adolescents. These are juveniles, not adults. Further, persons who have severe or long-standing type 2 diabetes may eventually become dependent on insulin therapy to maintain their health and—ultimately—life; thus, at this stage they become insulin-dependent. Also, occasionally type 1 diabetes begins in adulthood.

The surge in type 2 diabetes prevalence is fueled by an increasing obesity rate and sedentary lifestyles, both in children and adults. Many other people have less severe—although not medically insignificant—blood glucose elevation or insulin resistance. All these individuals are vulnerable, albeit to different extent, to long-term hyperglycemia complications.

Diabetes imposes a heavy health and economic burden. In 2007, the Centers for Disease Control and Prevention of the National Institutes of Health in the United States estimated that in the United States alone, diabetes has been diagnosed in approximately 24 million people. In 2007, in the United States alone, direct and indirect expenses related to diabetes were estimated to have been almost $175 billion. It is estimated that almost 6 million people have the disease but may not be aware that they do, and approximately 57 million people may have prediabetes—the earliest stage of diabetes.

People, who have prediabetes, do not have hyperglycemia throughout the day, but only when they are fasting (for example, when they wake up in the morning) or for some time immediately after they consume carbohydrates.

Over a decade ago, in the United States alone, diabetes was diagnosed in approximately 1 percent of all reproductive age women.1 In 2004, almost a quarter of those diagnosed with diabetes in the United States were women in the reproductive-age group (18–44 years). Forty-eight million Americans are projected to have diabetes by 2050, and diabetes in women has been projected to increase by two hundred and twenty percent from 2005 to 2050.2

Given these trends, the need for effective ideas and treatments to control the blood glucose level in diabetic women—including during their pregnancies—is likely to grow.

Chapter 2

What risks does diabetes pose to pregnant women?

Among reproductive age women, even those who are not actively trying to conceive may accidentally get pregnant because their contraceptive methods are ineffective. If diabetes is poorly controlled before or during pregnancy, a woman and her developing baby may be exposed to adverse effects from poor blood glucose control. Fortunately, pregnancy outcomes can be improved if diabetes is well controlled.

Compared to pregnant nondiabetic women, pregnant diabetic women are at higher risk for episodes and complications from severe hypoglycemia (abnormally low blood glucose reactions), multiple hospital stays, and hyperglycemia complications—worsening underlying diabetic end-organ disease, diabetic ketoacidosis, and higher likelihood to experience hypertension, anemia, infections, cesarean delivery, and poor wound healing.

The period in diabetic women’s lives during which they are pregnant is relatively short, and their pregnancies usually end satisfactorily—relieved health-care teams, happy and grateful mothers, and living and apparently healthy babies. Even if diabetic women’s blood glucose control during pregnancy was poor, attention often was focused almost entirely on their developing babies—not on them. Subsequently, live infants’ births were seen as ample success, and the mothers’ health-care teams were considered to have fully met their responsibilities.

Usually after these births, the mothers’ health-care teams are different from their children’s; thus, there often is not an opportunity—sometimes, not even an interest—for the same practitioners to attempt to identify important events that occurred before and during pregnancy and to connect them to health problems that develop later in these children’s lives.

Chapter 3

What risks does diabetes pose to developing babies?

Previously, most people assumed that if diabetic women’s babies were born alive and without malformed organs, they had escaped long-term or permanent adverse effects from maternal and fetal hyperglycemia and fetal hyperinsulinemia (abnormally high blood insulin level). Now, however, we know that this is not the whole story.

Traditionally, only developing babies’ short term adverse effects from hyperglycemia—a fetal diabetic disease syndrome—were considered to be clinically significant; for example, fetal organ malformation, abnormal fetal growth, and hypoglycemia episodes in newborn babies.

In fact, news that a baby has been born massively overweight—invariably its mother is diabetic—often is lauded in the media and by the lay public as an awesome triumph, rather than the sobering realization that this baby’s obesity resulted from undiagnosed or poorly managed diabetes during pregnancy and may actually be a harbinger of that child’s life being at higher risk for chronic ill health.

Substantial evidence has emerged to suggest that abnormal events during fetal developmental and growth may be the origin of childhood and adult cardiovascular and metabolic disease.3, 4 Thus, it is now widely appreciated, among other things, that babies that develop in an environment of persistent maternal hyperglycemia and/or intrauterine malnutrition are at increased risk for medical complications later in life.

Rightfully, this realization has led to a paradigm shift in how practitioners view poorly controlled diabetes during pregnancy, and its consequences—the fetal diabetic disease syndrome to which it may lead—and has resulted in more emphasis on how important it is for pregnant diabetic women to maintain normal blood glucose control before and for the full pregnancy duration—a goal that, with relevant knowledge and resources, can be achieved by many of these women.

Maintaining a normal blood glucose level before and during pregnancy is the most important strategy that practitioners and their diabetic patients can implement to ensure that these women’s developing babies will be healthy.

Chapter 4

How has insulin therapy in nonpregnant people been modified to treat pregnant women?

Rarely are pregnant women included in early studies regarding medications’ effectiveness to treat diabetic people. Typically, unless they are known to be detrimental to pregnant women or their babies, treatments developed for nonpregnant people’s diabetes care are adopted for use by pregnant women without being modified. Also, practitioners do not always agree that modifying these treatments will necessarily improve pregnancy outcomes.

Current knowledge and advances in insulin formulations and insulin delivery systems have improved our ability to achieve glucose targets in most diabetic people; progress that can benefit diabetic women during pregnancy, while limiting the complications that they and their developing babies are known to be more likely to experience.

If diabetic women’s health-care teams do not appreciate that differences in glucose metabolism during pregnancy require that they use a significantly different approach from those that they use for nonpregnant people, however, their patients may needlessly experience complications during pregnancy, and fail to achieve the full potential benefits from currently available treatment modalities.

Chapter 5

What modalities are available currently for insulin therapy for pregnant diabetic women?

It is well established in nonpregnant people, that it is important that they maintain normal blood glucose control, and if they do so, they reduce the likelihood that they will develop long-term diabetes complications.5, 6 Often, in combination with diet—medical nutrition therapy (MNT), self-monitoring of blood glucose (SMBG) level, and lifestyle adjustment—particularly, increased physical activity—insulin is recommended for adequate blood glucose control.

Intensive insulin therapy, although occasionally challenging, is necessary and effective in maintaining a normal blood glucose level in pregnant diabetic women.

Daily subcutaneous multiple injection therapy (MIT) and continuous subcutaneous insulin infusion (CSII)—insulin pump—are the modalities currently available for insulin therapy in general medical practice.

For several decades, MIT has been used to treat diabetes successfully: there is no doubt that it can be effective for many diabetic people if it used appropriately. Because MIT has been available for several decades, protocols for its use during pregnancy are, by and large, well established and widely used.

For women who already use or would consider using insulin pumps rather than MIT, however, detailed protocols, particularly, during pregnancy, have not been well described or widely accepted.

Chapter 6

What do research studies show regarding pregnancy outcomes in treated diabetic women?

Considerable research effort has been devoted to, among others, three specific areas:

How to identify women who could benefit from treating their hyperglycemia.

How to select treatments that can be effective in improving pregnancy outcome in these women.

How to measure the success, failure, or complications of these various treatments.

Generally speaking, in medical practice and research studies, diabetes during pregnancy has been divided into two broad categories: gestational and pregestational.

Gestational diabetes has been defined as glucose intolerance that first occurs or is first identified during pregnancy. The practical consequence of using a definition such as this one—and also, some might argue, an important limitation—is that at least two medically distinct subgroups of pregnant women are given this diagnosis.

One group comprises women whose blood glucose level or glucose control before pregnancy was normal, but who developed hyperglycemia only during the third pregnancy trimester: this many would consider, strictly speaking, true gestational diabetes.

Another group comprises women who had prediabetes or type 2 diabetes before they conceived, but who had not been diagnosed until the appropriate tests were first performed during a pregnancy. This group’s contribution to the larger group of women who are diagnosed with gestational diabetes is higher in communities in which many women have prediabetes or type 2 diabetes, or where most women are tested for diabetes only during pregnancy. Intuitively, one would expect that pregnancy risks and outcomes for these women would be closer to those experienced by women with pregestational diabetes.

There is potentially, a third group—pregnant women who coincidentally develop late-onset type 1 diabetes or one of various rare medical conditions that may affect the blood glucose level (e.g., an adrenal gland tumor—a pheochromocytoma). Even if in these cases the true diagnosis is apparent from the onset, traditionally these have been classified as gestational diabetes. Because this is an unusual presentation of both gestational and type 1 diabetes, these women are more likely to have missed or delayed diagnosis and complications resulting from inappropriate treatment. Fortunately, in all likelihood this group is extremely small.

To the extent that women who actually have type 1, prediabetes, or type 2 diabetes are misclassified as having gestational diabetes, the frequency at which specific adverse pregnancy outcomes associated with current treatments occur is likely to vary considerably.

Large, well-designed clinical studies have demonstrated convincingly that when diabetes first occurs during pregnancy, current treatments—dietary modification, blood glucose monitoring and, if necessary, insulin—improve pregnancy outcomes significantly.7, 8, 9 Considered together, these studies show that if appropriate modern treatment is given, stillbirth is rare, and the most common complications—excessive fetal growth, cesarean delivery, and newborn hypoglycemia—can be reduced significantly.

There is absolutely no doubt that diabetes that was present before a pregnancy began (i.e., pregestational diabetes), can affect pregnancy adversely and vice versa; after all, prior to the 1920s, when insulin was discovered and industrial mass production made it widely available to diabetic people, pregnancy in type 1 diabetic women often ended poorly for mother or fetus—and often both.

Although current treatments have been shown to improve pregnancy outcomes in women who have pregestational diabetes (particularly type 2), the evidence of this improvement is not always as consistent as it is for gestational diabetes; therefore, much effort continues to be expended to develop alternate treatments and care protocols.

In 1989, a multinational group of European diabetes experts met in Italy under the auspices of the World Health Organization and the International Diabetes Federation to discuss strategies to reduce the increasing adverse impact of diabetes in Europe. The principal outcome of this meeting was the St. Vincent Declaration10—a statement of goals that included one to achieve a pregnancy outcome in the diabetic woman that approximates that of the nondiabetic woman. Since then, however, the disparity remains—despite establishing high level regional diabetes in pregnancy care centers, pregnant diabetic women using various insulin formulations and delivery systems, advances in newborn intensive care, and widespread use of modern techniques for fetal health assessment.

Research studies that report the outcome of treating pregestational diabetes during pregnancy have yielded inconsistent results. Although reports from specialized diabetes in pregnancy care centers in North America and Western Europe show significant progress, the majority indicate that two decades later, the St. Vincent Declaration’s primary goal regarding pregnancy has not been achieved.11–27

Adequate blood glucose control affects pregnancy outcomes positively; therefore, protocols for insulin therapy that improve our ability to achieve such control during pregnancy are likely to contribute to reduce disparity in pregnancy outcomes.

Chapter 7

What are health-care teams’ roles in treating pregnant diabetic women?

Practitioners who care for diabetic women may not be skilled in using insulin pump therapy specifically during pregnancy—and diabetic pregnant women frequently encounter and can discern such practitioners. The belief that erratic blood glucose level is inevitable during pregnancy, or unjustified labeling diabetic women as impossible to control, brittle, or non-compliant, may encourage both pregnant women and their health-care teams to adopt a nihilistic attitude toward blood glucose control during pregnancy. This would be a mistake.

Often, without explicit verbalization, some practitioners hope that insulin pump users who get pregnant are able to correctly manage their pumps during pregnancy, labor, and delivery even as these women hope that their health-care teams know enough to get them through pregnancies—probably a previously completely unfamiliar experience for them—without complication. Ideally, in order to achieve the best outcome, both pregnant women and their health-care teams should be knowledgeable and involved in making recommendations regarding insulin prescription for pump use during pregnancy.

In my experience, many pregnant women who have diabetes—especially, type 1—and are insulin pump users, are among the most well-informed patients regarding their illness. This is not surprising, because erratic, extreme blood glucose level fluctuation can have a profoundly negative effect on people’s lifestyles, daily activities, and overall health. These women’s wish to avoid complications and bear healthy children enhances their motivation to maintain good blood glucose control, and this deserves to be complemented by appropriate expertise from their health-care team members.

Chapter 8

What do research studies show regarding how different insulin therapies affect health outcomes in diabetic people?

Over the past two decades, several reports have been published regarding insulin pump therapy during pregnancy. These studies confirmed that during pregnancy, pump therapy is an acceptable alternative to MIT28–40, but avoided discussing either therapy’s relative superiority or proposing a typical patient profile for which one or the other modality would be better suited, or protocols to guide practitioners or patients who wish to use insulin pump therapy during pregnancy.

Recently, one retrospective study reported that maternal diabetic ketoacidosis (DKA) and newborn hypoglycemia—both important pregnancy complications—occurred more frequently in pregnant women who used pump therapy, as compared to MIT.41 This conclusion has not been confirmed by others; but if true, it would be important for diabetic women and their health-care teams to know, because it is likely to