Current management of diabetic pregnancy
Unlike conventional therapy, intensive drug therapy plus self-monitoring diminishes adverse obstetric outcomes in all types of diabetes
IN THIS ARTICLE
New agents such as insulin analogs (mainly insulin lispro) and oral antidiabetic drugs (mainly glyburide) have profoundly altered the management of diabetes, producing obstetric outcomes comparable to those among the general population. Furthermore, in all types of diabetes, self-monitoring of blood glucose plus intensified drug therapy may help women achieve glycemic control and enhance perinatal outcomes at a lower cost than conventional management—and patients readily accept this approach.
This article describes the rationale for intensive treatment with these agents and other interventions to prevent both hypoglycemia and hyperglycemia.
Intensive therapy requires:
- memory-based self-monitoring of blood glucose, which empowers patients to take charge of glycemic control and provides feedback on the timing and dose of insulin administration,
- dietary regulation,
- strict criteria for initiation of pharmacologic therapy,
- multiple injections of insulin or its equivalent when diet alone is insufficient, and
- an interdisciplinary management team.
Two breakthrough studies in nonpregnant patients first showed the effectiveness of intensive therapy: the Diabetes Control and Complications Trial1 and the United Kingdom Prospective Diabetes Study.2,3 In the first, intensive therapy reduced the risk of retinopathy and lowered rates of microalbuminuria, albuminuria, and clinical neuropathy. In the second, intensive therapy substantially reduced the risk of microvascular complications.
Blood glucose goals
Regardless of the treatment, the primary goal is always to achieve glycemic control, because it reduces the incidence of hypoglycemia, hyperglycemia, and ketosis. For type 1 and type 2 diabetes, glycemic control is important to prevent further deterioration of complications such as vasculopathy and nephropathy.
Goals of treatment are achieving the following blood glucose concentrations (in milligrams per deciliter):
- mean: 90 to 105
- fasting: 60 to 90
- preprandial: 80 to 95
- postprandial: less than 120
At each visit, the clinician evaluates these values and, when necessary, increases the dose of insulin or the oral agent to meet these goals.4
In the process, the clinician needs to anticipate how pregnancy will affect preexisting disease, and how diabetes will affect pregnancy outcomes, in patients with any of the 3 types of diabetes.
2 diet protocols
For all types of diabetes, the foundation is diet—specifically, using nutritional therapy to achieve and maintain a maternal blood glucose profile comparable to that of a nondiabetic woman.
Two approaches are recommended:
- reducing carbohydrate intake to 40% to 50% of total calories or
- limiting carbohydrate consumption to foods with a low glycemic index for approximately 60% of calories.
Only women who achieve targeted levels of glycemic control improve insulin secretion and sensitivity. Those who fail to achieve it may exhibit slightly improved sensitivity, but do not attain the same level of insulin response and sensitivity as non-diabetic women. 4,5
Calculating calories: Same for all
- For a BMI less than 20 (underweight), daily caloric intake should be 35 to 38 kcal/kg.
- For a BMI of 20 to 25 (normal weight), the patient should consume 30 kcal/kg.
- For a BMI of 26 and higher (overweight, obese, morbidly obese), caloric intake should be 20 to 25 kcal/kg.
Calories per day are then calculated according to the patient’s weight during pregnancy and are adjusted throughout pregnancy as that weight increases.
In addition, the daily allotment of calories is divided into 3 main meals and 3 to 4 snacks, with adjustments for the patient’s time constraints, work schedule, and other individual factors.
To encourage compliance, the diet also should reflect the patient’s cultural preferences.
How do you know when diet fails?
Women with pregestational diabetes are usually already taking insulin or other pharmacologic agents by the time they conceive. There is no consensus or hard data on how long a woman who develops gestational diabetes mellitus should remain on a diet before starting drug treatment.
In a study evaluating the time required to achieve glycemic control with diet alone during a 4-week period, 70% of patients with fasting plasma below 95 mg/dL achieved established levels of glycemic control within 2 weeks with no substantial improvement thereafter. 8,9 In contrast, in patients with fasting plasma glucose of more than 95 mg/dL, most patients failed to achieve the desired level of glycemic control throughout the 4-week period.
Hypoglycemia after exercise can be a positive marker
I recommend 20 to 30 minutes of exercise 3 to 4 times weekly for gravidas with diabetes, provided they are willing and able to perform it, because it can improve post-prandial blood glucose levels and insulin sensitivity.12
Blood glucose should be measured after exercise, especially in women with type 1 diabetes.
Hypoglycemic reactions during and after exercise may be positive markers of improved insulin sensitivity. Low blood glucose necessitates adjustment of the insulin dose and carbohydrate intake. Extra monitoring is warranted after evening exercise, as glucose uptake increases for several hours after exercise and can cause nocturnal hypoglycemia.
Intensive therapy: Why, when, how
The healthy body secretes insulin over 24 hours independent of nutrient intake. Basal insulin secretion maintains metabolic homeostasis by preventing excessive hepatic glucose production and the mobilization of free fatty acids from adipose tissue stores. This also helps maintain protein balance. Insulin secretion increases several times in response to the ingestion of food.
INTEGRATING EVIDENCE AND EXPERIENCE
Treatment or consequences
Langer O, Yogev Y, Most O, et al. Gestational diabetes: The consequences of not treating. Am J Obstet Gynecol. 2005;192;989-997.
On the other hand, maternal hyperglycemia and resultant fetal hyperinsulinemia are central to the pathophysiology of diabetic complications:
- type 1 and type 2 diabetes—congenital malformations
- all pregnancies compromised by diabetes—increased rates of deviant fetal growth (macrosomia and intrauterine growth restriction), neonatal metabolic, hematological and respiratory complications, birth trauma, stillbirth, cesarean delivery and intensive care admissions.
I tell patients, “Some improvement is better than none” I explain to my patients how pregnancy itself imposes risk, and why it is crucial to follow protocols and achieve glycemic control. I explain the maternal and fetal complications associated with various glucose thresholds, and the added risks of maternal age, body composition, disease severity, and so on.
However, I also stress that even some improvement in glucose control is better than no improvement.
In the diabetic patient, the aim of intensive insulin therapy is to mimic normal physiology. Basal insulin is provided by administration of NPH, Lente, or Ultralente at bedtime and sometimes before breakfast as well. Insulin also is given before meals (0 to 15 minutes before for lispro, or 30 to 45 minutes before for regular insulin). This algorithm is the foundation of intensive therapy, which involves multiple injections daily versus 1 or 2 injections for conventional therapy.
Insulin dosage requires frequent adjustment
To determine the insulin dose needed to achieve glycemic control in pregnant gravidas, multiple blood glucose measurements are needed because insulin requirements steadily increase throughout pregnancy in women with pregestational diabetes.13-16 Jovanovic and Peterson13 quantified these increases as 0.7, 0.8, 0.9, and 1.0 U/kg per day in the first trimester and at weeks 18, 26, and 36, respectively.
Using memory-based reflectance meters to monitor blood glucose, my colleagues and I observed that insulin requirements during pregnancy in women with pregestational diabetes are triphasic (TABLE) and require frequent assessment with individualized adjustment of the insulin dose in each trimester. 16 Women with type 2 diabetes require significantly higher doses of insulin each trimester, compared with women with type 1 diabetes.
In women with gestational diabetes, we observed a biphasic increase in insulin requirements17:
- Insulin requirements increased up to the 30th week of gestation, necessitating frequent dose adjustments.
- After 30 weeks, insulin requirements stabilized, requiring minimal or no dose adjustments. Insulin requirements for obese subjects were 0.9 U/kg per day, compared with 0.8 U/kg per day for nonobese women.
The actual insulin dose varied more for obese than for nonobese women.
Insulin requirements during pregnancy for women with pregestational diabetes
INSULIN REQUIREMENT (UNITS/KG/DAY)
TYPE 1 DIABETES
TYPE 2 DIABETES
Insulin requirements vary with gestational diabetes
When to start drugs
Most women with pregestational diabetes are treated with insulin prior to pregnancy. Thus, the main task during pregnancy is maintaining or improving glycemic control. In gestational diabetes, pharmacologic therapy (insulin or glyburide) is initiated only when regulation of the diet fails to achieve the desired level of glycemic control or when the disease is severe enough to mandate therapy.
Authorities disagree on the threshold of severity that necessitates pharmacologic intervention (glyburide or insulin). Some suggest a threshold of fasting plasma glucose of at least 95 mg/dL,18-20 which will decrease the rate of macrosomic and large-for-gestational-age infants,19,21 while others suggest at least 105 mg/dL.19,22
All authorities agree that drug therapy should be started when postprandial glucose levels are 120 mg/dL or higher at 2 hours or 140 mg/dL or higher at 1 hour.
Using these standards, 30% to 50% of women with gestational diabetes require pharmacologic therapy when diet alone fails to reduce glucose levels.
Determining insulin requirements
The insulin algorithm for women with gestational diabetes is based on prepregnancy BMI:
- For women with a BMI of 25 and less, the insulin dose is 0.8 U/kg.
- For women with a BMI of more than 25 (overweight and obese), it is 1.0 U/kg.
For example, a woman at 28 weeks’ gestation who currently weighs 85 kg and who is classified as overweight or obese on the basis of her prepregnancy BMI, would be given an insulin dose of 85 U (85 kg×1 U).
Once the total insulin dose is calculated, it is divided so that two thirds is administered in the morning and one third in the afternoon or evening. The morning dose is further divided in a ratio of 2 to 1 (intermediate and rapid-acting) and the evening dose into a ratio of 1-to-1 (rapid-acting and intermediate). The rapid-acting dose is administered with the evening meal, while the intermediate dose is given just before bedtime.
If the patient with gestational diabetes has not achieved the desired level of glycemic control after 3 to 7 days, increase the total dose by 10% to 20% and thereafter adjust it when needed.
Fine points of insulin therapy
The actual total insulin dose in women with gestational diabetes is 40% higher than the calculated dose16; this provides a margin of safety and avoids severe hypoglycemic episodes. As a rule of thumb, self-monitoring of blood glucose is necessary before every administration of insulin.
The failure to introduce insulin therapy in a timely fashion may lead to fetal hyperinsulinemia and associated complications. Conversely, premature initiation of insulin in women who could have achieved glycemic control with diet alone leads to unnecessary drug treatment.
When gestational diabetes is diagnosed after 30 to 33 weeks’ gestation and there is little time left to gain the desired level of control, pharmacologic intervention is recommended. There is greater flexibility when gestational diabetes is diagnosed early in the third trimester.