DIABETES MELLITUS AND PREGNANCY

Background

Abnormal maternal glucose regulation occurs in 3-10% of pregnancies. Studies suggest that the prevalence of diabetes mellitus (DM) among women of childbearing age is increasing in the United States. This increase is believed to be attributable to more sedentary lifestyles, changes in diet, continued immigration from high-risk populations, and the virtual epidemic of childhood and adolescent obesity that is presently evolving in United States. Gestational diabetes mellitus (GDM) is defined as glucose intolerance of variable degree with onset or first recognition during pregnancy. Gestational diabetes mellitus accounts for 90% of cases of diabetes mellitus in pregnancy. Type II diabetes mellitus accounts for 8% of cases of diabetes mellitus in pregnancy, and given its increasing incidence, preexisting diabetes mellitus now affects 1% of pregnancies.
Infants of mothers with preexisting diabetes experience double the risk of serious injury at birth, triple the likelihood of cesarean delivery, and quadruple the incidence of newborn intensive care unit admission. Studies indicate that the risk of these morbidities is directly proportional to the degree of maternal hyperglycemia. For this reason, the excessive fetal and neonatal morbidity attributable to diabetes in pregnancy should be considered preventable with early diagnosis and effective treatment therapies.

Pathophysiology

Maternal-fetal metabolism in normal pregnancy

With each feeding, the pregnant woman undergoes a complex series of maternal hormonal actions (ie, a rise in blood glucose; the secondary secretion of pancreatic insulin, glucagon, somatomedins, and adrenal catecholamines). These adjustments ensure that an ample, but not excessive, supply of glucose is available to the mother and fetus. The key features of this complex interaction include the following:

• Compared to nonpregnant subjects, pregnant women tend to develop hypoglycemia (plasma glucose mean = 65-75 mg/dL) between meals and during sleep. This occurs because the fetus continues to draw glucose across the placenta from the maternal bloodstream, even during periods of fasting. Interprandial hypoglycemia becomes increasingly marked as pregnancy progresses and the glucose demand of the fetus increases.
• Levels of placental steroid and peptide hormones (eg, estrogens, progesterone, and chorionic somatomammotropin) rise linearly throughout the second and third trimesters. Because these hormones confer increasing tissue insulin resistance as their levels rise, the demand for increased insulin secretion with feeding escalates progressively during pregnancy. Twenty-four–hour mean insulin levels are 50% higher in the third trimester compared to the nonpregnant state.
• If the maternal pancreatic insulin response is inadequate, maternal and, then, fetal hyperglycemia results. This typically manifests as recurrent postprandial hyperglycemic episodes. These postprandial episodes are most significantly accountable for the accelerated growth exhibited by the fetus.
  Surging maternal and fetal glucose levels are accompanied by episodic fetal hyperinsulinemia. Fetal hyperinsulinemia promotes excess nutrient storage, resulting in macrosomia. The energy expenditure associated with the conversion of excess glucose into fat causes depletion in fetal oxygen levels.
• These episodes of fetal hypoxia are accompanied by surges in adrenal catecholamines, which, in turn, cause hypertension, cardiac remodeling and hypertrophy, stimulation of erythropoietin, red cell hyperplasia, and increased hematocrit. Polycythemia (hematocrit >65%) occurs in 5-10% of newborns of diabetic mothers. This finding appears to be related to the level of glycemic control and is mediated by decreased fetal oxygen tension. High hematocrit values in the neonate lead to vascular sludging, poor circulation, and postnatal hyperbilirubinemia.

During a healthy pregnancy, mean fasting blood sugar levels decline progressively to a remarkably low value of 74 ± 2.7 (SD) mg/dL. On the other hand, peak postprandial blood sugar values rarely exceed 120 mg/dL. Meticulous replication of the normal glycemic profile during pregnancy has been demonstrated to reduce the macrosomia rate. Specifically, when 2 hour postprandial glucose levels are maintained less than 120 mg/dL, approximately 20% of fetuses demonstrate macrosomia. Conversely, if postprandial levels range up to 160 mg/dL, macrosomia rates rise to 35%.

Frequency

United States

In the United States today, 21 million people (7% of the population) have some form of diagnosed diabetes. Another 6 million people may be undiagnosed. Approximately 3-10% of pregnancies in the United States are complicated by diabetes, of which 90% is gestational diabetes and 8% is preexisting, insulin-resistant (ie, adult-onset) diabetes. The incidence of insulin-resistant diabetes is increasing markedly in the United States, probably related to rising population obesity and shifts in ethnicity.In addition to these factors contributing to a rise in the prevalence of diabetes among reproductive aged women, medical interventions during pregnancy may increase the likelihood of developing gestational diabetes. A study reported in 2007 has demonstrated and increased incidence of gestational diabetes mellitus in women receiving prophylactic 17 alpha-hydroxyprogesterone caproate for the prevention of recurrent preterm delivery (from 4.9% in control to 12.9% in treated patients).1

Race

The prevalence of gestational diabetes is strongly related to the patient's race and culture.

• Prevalence rates are higher in African, Hispanic, Native American and Asian women than in white women.
• Typically, only 1.5-2% of Caucasian women develop gestational diabetes mellitus, while Native Americans from the southwestern United States may have rates as high as 15%.
• In Hispanic, African American, and Asian populations, the incidence is 5-8%.
• In these high-risk populations, the recurrence risk with future pregnancies has been reported to be as high as 68%.2 In addition, approximately one-third will develop overt diabetes mellitus within 5 years of delivery, with higher risk ethnicities having risks nearing 50%.3
• Race also influences many complications of diabetes mellitus in pregnancy. For instance, African Americans have been shown to have lower rates of macrosomia, despite similar levels of glycemic control. Conversely, Hispanic women have higher rates of macrosomia and birth injury than women of other ethnicities, even with aggressive management.4, 5

To be continue..............