Diabetes is a significant public health challenge for the United States. According to the 2014 report from the Centers for Disease Control (CDC), in the United States¹:

Like diabetes, obesity is a national epidemic with an increase in both prevalence and incidence. Rates of obesity and diabetes parallel each other. In states where obesity is >29%, diabetes is >9%. In 2013, these rates existed in 45 states.² Obesity is one of the highest risk factors for the development of T2DM.³ Age, gender, and race also affect the prevalence of diabetes. Diabetes is increased in pregnant women >25 years of age and in non-Hispanic Blacks, Hispanic/Latino Americans, American Indians, East Indians, Alaska Natives, Asian Americans, and Native Hawaiian and Pacific Islanders (Table 13.1).^1,4

During pregnancy, 90% of all cases of diabetes are women with gestational diabetes mellitus (GDM). Approximately 9.2% of pregnant women in the United States are diagnosed with GDM.⁵ Depending on race and ethnicity of the population, and upon method of diagnosis, the prevalence may range from 2% to 18%.^1,5 Within the postpartum period 5% to 10% of women with GDM are found to have diabetes, usually type 2.⁶

Women with a history of GDM have a 35% to 60% chance of developing T2DM within the 10 to 20 years of the index pregnancy. GDM represents one of the highest risk factors for developing T2DM.³

In 1997, the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus eliminated the old categories of insulin-dependent diabetes mellitus (IDDM) and non–insulin-dependent diabetes mellitus (NIDDM) and established new terminology based on pathophysiology and not on use of insulin (Table 13.2).

NOTE: Our current terminology uses the Arabic 1 and 2 (type 1 and type 2) instead of the Roman numerals I and II.

In 2003, the committee recognized two categories in which glucose metabolism is defective—impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). IFG and IGT are risk factors for future diabetes and cardiovascular disease. Blood glucose values indicative of prediabetes are values above the normal range but not in the range of overt diabetes. This category is important because these BG values are associated with other metabolic disorders such as obesity, hyperlipidemia, cardiovascular disease, and polycystic ovarian syndrome. Prediabetes (preDM) is similar to gestational diabetes. They both share the pathophysiology of T2DM and they are both primarily treated with lifestyle interventions: healthy eating and being active. Each condition has a conversion rate to T2DM of about 50% over the subsequent 10 years after diagnosis. In the Diabetes Prevention Program, people with prediabetes who are treated with diet, exercise and/or, metformin delayed T2DM beyond 5 years.^7,8,9 (See Table 13.3 for the categories associated with an increased risk for diabetes.)

The primary categories of diabetes include T1DM and T2DM with GDM and prediabetes as high-risk conditions leading to T2DM. While there are other less common categories of diabetes, the following table will summarize the characteristics of T1DM, T2DM, PreDM, and GDM. See Table 13.4: characteristics of diabetes, prediabetes, and gestational diabetes. Understanding the differences and similarities between these categories is essential to the optimum care of women with diabetes during pregnancy. The common denominator among all categories of diabetes is hyperglycemia and its adverse effects.

Effects of diabetes on women are unique because hyperglycemia can affect not only the woman’s health but also that of her unborn child and that child’s lifelong health. During pregnancy, women with pre-existing diabetes, type 1 (T1DM) and type 2 (T2DM), have the most risk for perinatal morbidity and mortality. Risks to the fetus depend on the level and severity of maternal hyperglycemia prior to pregnancy, during the time of conception, and throughout gestation.^12,13 If glycemic control is poor (HbA1C >7%) during conception and in the first trimester during organogenesis (first 8 weeks’ gestation, when major organs are developing), congenital anomalies or miscarriage can occur. Miscarriage rates for women with pre-existing diabetes are as high as 30%. Cardiac and neural tube defects are the most common malformations.¹⁴

Hyperglycemia during the second and third trimesters of pregnancy can result in excessively large babies posing short- and long-term risks to both mother and child. These risks affect women with T1DM, T2DM, and GDM.^15,16,17

This is the result of elevated maternal blood glucose freely crossing the placenta while insulin cannot. The fetus then produces its own insulin resulting in hyperinsulinemia. High levels of insulin combined with high levels of glucose in the fetus result in storage of excess fat in the abdomen of the fetus leading to macrosomia.^18,19 The third trimester is the time of rapid weight gain, development of muscle mass and fat stores for the newborn.

Congenital malformations are not common in GDM. Maternal hyperglycemia generally develops at the end of the second trimester when placental hormones increase maternal insulin resistance. Maternal insulin secretion must double to maintain normoglycemia.¹¹ Insulin resistance will continue to rise through the third trimester, often tripling the requirement for insulin secretion from the pancreas. Women with normal carbohydrate metabolism are able to produce enough endogenous insulin to maintain normoglycemia. Women with defective carbohydrate metabolism have mild–severe hyperglycemia depending on the severity of their defect. For this reason, screening for GDM is recommended at 24 to 28 weeks’ gestation for all pregnant women who have not
already been diagnosed with diabetes or hyperglycemia.^20,21 See Table 13.5 that outlines adverse effects of hyperglycemia on pregnancy outcomes during the second half of pregnancy.

For over 50 years in the United States, the diagnosis of diagnosing gestational diabetes (GDM) has been based on criteria that predict the future risk of the mother for developing T2DM. O’Sullivan and Mahan focused on subsequent maternal disease in 1,700 women using a 100-g OGTT at 28 weeks’ gestation.²⁴ Diagnosing GDM has been based on identifying women at risk for type 2 diabetes in their future and not on perinatal outcomes. Blood glucose cutoffs for the 3-hour, 100-g OGTT were based on a statistical calculation and not on levels of glycemia with increasing risks for adverse outcomes. The 3-hour OGTT cutoffs have been adjusted as blood glucose laboratory determination has changed. The last adjustment was made by Carpenter and Coustan in 1982 and was adopted by ACOG and ADA.

Countries in most of the world have used a 2-hour, 75-g OGTT using various blood glucose cut points derived in various ways. Inconsistent diagnosing criteria across the world preclude any accurate study of GDM; therefore we cannot apply study findings universally limiting the development of best practices.

Overt diabetes, characterized by moderate to severe hyperglycemia, clearly increases the risk of adverse pregnancy outcome. In order to know who and when to treat mild hyperglycemia (AKA GDM), one must know what level of glucose intolerance during pregnancy, short of diabetes, is associated with the risk of adverse perinatal outcomes. This information could help to develop a global, evidence-based method of diagnosing GDM. The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study published in 2008 focused on fetal effects of maternal hyperglycemia in 25,505 pregnant women at 15 centers in 9 countries using a 2-hour, 75-g OGTT at 24 to 28 weeks’ gestation. The HAPO epidemiologic study was the first to conclusively establish a relationship between maternal glucose concentrations and undesirable perinatal outcomes (macrosomia, neonatal hyperinsulinemia, neonatal hypoglycemia, and preeclampsia) in women not previously diagnosed with diabetes. There was a continuous, positive, independent relationship between maternal BG and percent newborn body fat and between cord C-peptide concentrations and percent newborn fat. This suggests that the relationship between maternal glycemia and fetal fat deposition is mediated by fetal insulin production.²⁵

The International Association of Diabetes in Pregnancy Study Group (IADPSG) convened a group of experts to translate the findings of the HAPO study to a method of diagnosing GDM that could be used globally. In 2010, the recommendations suggested BG cut points which represented an odds ratio of 1.75 of risk to experience the adverse outcomes. A one-step, 2-hour Oral Glucose Tolerance Test (using 75 g of Glucola) was recommended to be administered to all pregnant women, not previously diagnosed with diabetes at 24 to 28 weeks’ gestation. Blood glucose cut points were as follows: fasting ≥92 mg/dL, 1 hour, ≥180 mg/dL, and 2 hour ≥153 mg/dL. GDM
is diagnosed if 1 value is abnormal. The ADA adopted the one-step method in 2011 but ACOG chose to stay with the two-step method (Table 13.6).

The IADPSG criteria will identify approximately 18% of all pregnant women in the United States as having GDM.²⁶ This was thought to place an undue demand on the provider, healthcare system, and the woman’s pregnancy. The controversy continues until more data can be supplied which supports the identification and treatment of this high-risk group of woman and their offspring. Currently, the World Health Organization, American Diabetes Association, ACE, and many countries in Europe and Asia have adopted the IADPSG guidelines.

The ADA and ACOG agree that women with high risk factors for T2DM should be tested for undiagnosed type 2 diabetes at the first prenatal visit using one of the methods of diagnosing diabetes in the nonpregnant population (see Table 13.2 for diagnosing diabetes in the nonpregnant population). This recommendation makes it possible to diagnose T2DM (and rarely T1DM) in pregnancy so that aggressive treatment can begin early and women with undiagnosed overt diabetes can be identified and appropriately followed up postpartum.²⁶

The nutritive substance used in the greatest quantities by humans is carbohydrate. Carbohydrates (CHO) are ingested with the food we eat or produced by our liver. After being converted into glucose, CHO is utilized by all our cells, especially by our muscles, which should constitute nearly half our body mass.

Production and consumption of CHO is so well regulated that a constant BG level is maintained between approximately 70 and 110 mg/dL. The constancy of the BG level is controlled by a complex physiological homeostatic mechanism because BG level is such an important factor in many chemical and physiological processes.

Normal glucose metabolism involves the following pathways

The balance between these two hormones (insulin and glucagon) holds metabolism “on the line,” promoting a stable homeostasis of glucose in the blood.

Many metabolic changes occur during pregnancy to optimize the growth of the fetus. Because the fetus depends entirely on the mother for its supply of energy, maternal adaptations must occur to increase glucose supply to the fetus. Initially human chorionic gonadotropin (HCG) stimulates the corpus luteum (the part of the follicle left behind in the ovary during ovulation) to produce estrogen and progesterone in the first 10 weeks after conception, until the placental cells can do so by themselves. By approximately 8 to 15 weeks’ gestation glucose homeostasis is altered by the increases in estrogen and progesterone that cause pancreatic β-cell hyperplasia (multiplication of cells), with subsequent increased insulin secretion. Since insulin resistance has not yet developed, women with pre-existing diabetes often experience hypoglycemia as a result of the following factors:

In the second and third trimesters, levels of human placental lactogen (HPL), human placental growth hormone (hPGH), progesterone, estrogen, tumor necrosis factor alpha (TNF-α), leptin, and cortisol increase progressively and cause increasing tissue resistance to insulin action.¹¹

Maternal cells are “blinded” by placental hormones inhibiting recognition of insulin. As hormone levels rise, insulin resistance increases and the maternal pancreas secretes more insulin. Maternal hyperinsulinemia provides the fetus with adequate substrate to grow (Glucose). Normal pregnancy can be viewed as a progressive condition of insulin resistance, hyperinsulinemia,
and mild postprandial hyperglycemia. The mild postprandial hyperglycemia serves to increase the amount of time that maternal glucose levels are elevated above the basal after a meal, thereby increasing the flux of ingested nutrients from mother to the fetus and enhancing fetal growth.

Maternal hyperglycemia (diabetes during pregnancy) results when the mother’s cells already have trouble recognizing insulin (insulin resistance) as in T2DM, prediabetes, polycystic ovarian syndrome, metabolic syndrome, obesity, or a pre-existing inherited tissue defect. Insufficient insulin secretion may also be a factor in maternal hyperglycemia when the woman’s pancreas cannot produce the extra insulin needed to meet increasing pregnancy demands.

Throughout pregnancy, there is an increased risk for fasting ketosis due to the following metabolic factors during pregnancy that allow energy to come from sources other than carbohydrates such as fats and protein (protects fetus from lack of carbohydrate):

These metabolic factors cause increased fat breakdown, and decreased maternal glucose production in the fasting state. This allows for increased utilization of fat stores for maternal energy, therefore protecting muscle mass from breakdown.

Just as healthy eating is essential to the management of hyperglycemia for all types of diabetes, exercise must also be incorporated into the plan of care. Being active for 30 to 60 minutes per day is encouraged because muscle activity does the following:

The goal of antepartum management is to achieve BG values as close to normal as is safe to reduce the risk of adverse perinatal outcomes. The BG values, which have the most significant effect on fetal macrosomia and cesarean birth are the fasting and the peak BG after a meal.^34,35

The HAPO study found that 11.9% of pregnant women had a fasting BG greater than 90 mg/dL in the beginning of the third trimester. This cutoff detected 22.1% of LGA neonates and 15.1% of primary cesarean deliveries.¹⁹ Nondiabetic, pregnant women wearing a continuous glucose monitoring system (CGMS) were shown to have a peak postprandial time (min) 70 ± 13.³⁶ In diabetic and nondiabetic pregnancies, maximal postprandial glucose excursions occur between 60 and 90 minutes after meal ingestion and correlate more closely with 1- than 2-hour postprandial measurements.³⁶ Some authors suggest that 60 minutes is a reasonable time to identify the peak postprandial since it is easier for women to remember and is closest to the average time from first bite of carbohydrate to peak BG.^35,37 Therefore, checking the 1-hour BG after the first bite of carbohydrate has been selected to represent the peak for most diabetes in pregnancy programs.

In an earlier study Langer found that when the mean daily BG value was 87 to 100 mg/dL, the rate of large for gestational age (LGA) and macrosomia was comparable to that in the general population, which is approximately 10%. Of importance to note is that fasting hyperglycemia greater than 105 mg/dL is associated with an increased risk of intrauterine fetal death (IUFD) in the last 4 to 8 weeks’ gestation.³⁸ When the mean BG was greater than 105 mg/dL the incidence of LGA increased more than twofold. The HbA1c had no relationship in the third trimester to these outcomes and could not be used to evaluate thresholds for improving outcomes in terms of macrosomia.³⁹

Establishing target BG has been challenging. While the fasting BG target of less than 90 mg/dL is somewhat evidenced based²⁶ there are no studies that show how close to “normal” the peak postprandial should be to show a significant improvement in outcomes (see Table 13.7).