Despite recent advances in the evaluation and medical treatment of diabetes in pregnancy, diabetic ketoacidosis (DKA) remains a matter of significant concern. The fetal loss rate in most contemporary series has been estimated to range from 10% to 25%. Fortunately, since the advent and implementation of insulin therapy, the maternal mortality rate has declined to 1% or less. In order to favorably influence the outcome in these high-risk patients, it is imperative that the obstetrician/provider be familiar with the basics of the pathophysiology, diagnosis, and treatment of DKA in pregnancy.

DKA is characterized by hyperglycemia and accelerated ketogenesis. Both a lack of insulin and an excess of glucagon and other counter-regulatory hormones significantly contribute to these problems and their resultant clinical manifestations. Glucose normally enters the cell secondary to the effects of insulin. The cell then may use glucose for nutrition and energy production. When insulin is lacking, glucose fails to enter the cell. The cell responds to this starvation by facilitating the release of counter-regulatory hormones, including glucagon, catecholamines, and cortisol. These counter-regulatory hormones are responsible for providing the cell with an alternative substrate for nutrition and energy production. By the process of gluconeogenesis, fatty acids from adipose tissue are broken down by hepatocytes to ketones (acetone, acetoacetate, and β-hydroxybutyrate [BHB] = ketone bodies), which are then used by the body cells for nutrition and energy production (Fig. 11-1). The lack of insulin also contributes to increased lipolysis and decreased reutilization of free fatty acids, thereby providing more substrate for hepatic ketogenesis. A basic review of the biochemistry involving DKA is presented in Fig. 11-1.

Now that we have an understanding of how and why ketone bodies are produced during DKA, what are the maternal consequences resulting from excessive ketogenesis? In general, ketone bodies are considered to be moderately strong acids. In response to the fall in pH in most body fluids created by an accumulation of these acids, the body reacts physiologically to correct the resultant metabolic acidosis. The respiratory rate and depth increase (Kussmaul respirations) in an attempt to blow off carbon dioxide, initiating a corrective trend toward compensatory respiratory alkalosis. Serum bicarbonate levels decline, and as a result, the anion gap becomes abnormally elevated. In addition to increasing fatty acid production, poor glucose utilization results in severe hyperglycemia. Untreated hyperglycemia leads to marked glycosuria, initiating a significant osmotic diuresis. As a result, dehydration, electrolyte depletion, and, if left untreated, cardiac failure and death may follow.

A vicious cycle is created by an increase in dehydration-mediated serum hyperosmolarity and catabolism, propagated by Kussmaul respiration, leading to a further production of glucose counter-regulatory hormones, lipolysis, and subsequent hyperketonemia. An algorithm for this clinical pathophysiologic response is presented in Fig. 11-2.

The fetus appears to be at significant risk of sudden intrauterine death during an episode of maternal DKA. The mechanism for this sudden death is not completely understood; however, it appears to be related to a combination of factors. Alterations in fetal fluid and electrolyte balance, poor uterine perfusion resulting from maternal hypovolemia, and increased acid load in the form of fatty acids and lactate, all favor a reduction in fetal oxygenation and metabolic acid clearance. When caring for a patient in DKA who is carrying a potentially viable fetus, careful fetal monitoring should be judiciously used. Often, signs of fetal stress become apparent, reflecting the degree of maternal metabolic derangement. Decreased variability and late decelerations in the fetal heart tracing as well as abnormal umbilical artery Doppler values are among the changes that can be observed. Delivery of a compromised baby should be prudently delayed until the mother is metabolically stable. Timely correction of maternal metabolic abnormalities generally results in a rapidly improved fetal condition, and may prevent fetal neuronal injury. Therefore, efforts should be directed at improving maternal clinical status and reserving emergency operative intervention for persistent fetal compromise. As BHB can cross the placenta and accumulate in the fetal brain, with reports of neuronal injury in some fetuses and neonates, the pediatric team should be informed of current or previous DKA during pregnancy. Moreover, in the case of antenatal resolution of an episode of DKA, the fetus should be monitored periodically throughout pregnancy by sonography for encephalomalacia (eg, ventriculomegaly and periventricular calcifications).

In pregnancy, DKA may occur at a lower plasma glucose value as compared to the nonpregnant patient and uncommonly occur as euglycemic DKA (blood glucose level less than 200 mg/dL). DKA has been observed at plasma glucose levels as low as 164 mg/dL. It appears that a relative insulin resistance of pregnancy combined with a greater tendency toward ketosis reduces the threshold for DKA during pregnancy. The insulin resistance during pregnancy is related to an increased production of placental hormones, progesterone, insulinase, and cortisol (Fig. 11-3). Respiratory alkalosis of pregnancy and a decreased renal buffering capacity of bicarbonate serve to worsen the complications associated with DKA.

The maternal and fetal concerns resulting from DKA emphasize the importance of a rapid and reliable diagnosis. The diagnosis of DKA should be based on clinical examination and supported by an evaluation of biochemical parameters. Table 11-1 summarizes the clinical presentation, biochemical definition, and laboratory findings associated with DKA.