Current management of diabetic pregnancy
Unlike conventional therapy, intensive drug therapy plus self-monitoring diminishes adverse obstetric outcomes in all types of diabetes
The carbohydrate algorithm. For every 15 g of carbohydrates ingested at mealtime, 1 U of rapid-acting insulin analog (insulin lispro or insulin aspart) is required.
If postprandial glucose is continuously elevated (>120 mg/dL) at 2 hours, an increase in rapid-acting insulin is required. Thus, the carbohydrate algorithm may change to 1 U of insulin for every 12 g of carbohydrates until the appropriate ratio is achieved.
If hypoglycemia or relative hypoglycemia occurs, the amount of carbohydrates should increase for each unit of insulin. For example, the adjusted dose would be 1 U of insulin for every 18 g of carbohydrates.
The range of these algorithms is influenced by prepregnancy BMI, disease severity, type of diabetes, and type of carbohydrate (ie, complex versus simple).41
Recognizing patterns of severity. The second algorithm involves identifying the glucose severity pattern (ie, hyperglycemia, hypoglycemia). For example, the total dose of insulin required (0.8–1.0 U/kg) is divided into a ratio of 60% for intermediate or long-acting insulin (basal dose) and 40% for the premeal dose. If the glucose level falls above the targeted level, a single unit of insulin lispro or insulin aspart is added for every 30 mg/dL, but not exceeding 3 U at one time. If glucose levels remain high, redistribute the calculated insulin dose to obtain an improved actual dose (ie, reconfigure the new calculated dose throughout the day based on patient need).
Retinopathy
Poor glucose control may contribute to or worsen diabetic retinopathy—the leading cause of blindness in diabetic patients 24 to 64 years of age—by increasing intracellular accumulation of glucose and its metabolic products. This damages the tiny blood vessels inside the retina, beginning with the formation of microaneurysms and progressing to blockage and, potentially, proliferation of fragile, abnormal, new blood vessels. If vessels leak blood, vision can be severely impaired or obliterated.
Patients at risk should achieve glycemic control gradually. Rapid initiation of stringent glycemic control can cause short-term progression of retinopathy, especially in hypertensive patients, although there are no apparent long-term effects.
Diabetic nephropathy
This complication increases the risk of preeclampsia, chronic hypertension, and fetal growth restriction, and is the most common cause of end-stage renal disease. Proteinuria often increases during pregnancy in diabetic women, but renal function generally remains stable. Nevertheless, advanced diabetic nephropathy (serum creatinine >1.5 mg/dL or creatinine clearance of ≤90 mL/min) can cause further deterioration.
The stacking effect explains why most women with gestational diabetes need no regular or rapid-acting insulin at lunchtime yet are still able to maintain the desired level of glucose control.
Special needs in type 1 disease
Because glucose levels in women with type 1 diabetes typically vary widely on a daily or even hourly basis, the insulin dose should be flexible. For example, the patient may need 1 U of rapid-acting insulin for every 25 mg/dL of blood glucose above 125 mg/dL, or 1 U for every 20 mg/dL above 120 mg/dL, and so on. I encourage patients to titrate based on half-unit increments, which can be measured in an insulin syringe.
Insulin pumps. Insulin lispro and insulin aspart are approved for administration as a continuous subcutaneous infusion. However, use of the pump in pregnancy has been limited—as has its research.
Improved metabolic control is a potential advantage of the pump. When the patient is motivated and alert, use of the pump can reduce nocturnal hypoglycemia and morning hyperglycemia caused by the “dawn phenomenon” (an abrupt rise in glucose level in the early morning).
Disadvantages of the pump include cost, diabetic ketoacidosis, and hypoglycemia (caused by malfunction or infection at the infusion site). Maternal and fetal outcomes are comparable whether the insulin pump or intensive therapy is used. However, improvements in lifestyle and metabolic control may justify use of the pump in women who have trouble achieving glycemic control.43
The many advantages of glyburide
Oral agents can be a pragmatic alternative to insulin in pregnancy because they are easy to administer and noninvasive. Many experts and authoritative bodies in the US recommend glyburide (sulfonylurea) as an alternative pharmacologic therapy during pregnancy.20,44-48 Others recommend further evaluation.19,22,49,50
Although some oral agents cross the placenta, they do not necessarily cause a toxic or teratogenic effect on the fetus. Glyburide, a class B drug, does not cross the placenta.51-53 It increases insulin secretion and diminishes insulin resistance by lowering glucose toxicity. Its onset of action is about 4 hours, and the duration of action is about 10 hours. Thus, after achieving the targeted therapeutic level, glyburide covers the basal requirement as well as postprandial glucose excursions.
