Glucose control in pregnant women with type 1 diabetes mellitus: Studies using a continuous glucose monitoring system

Abstract

Pregnancy in women with type 1 diabetes mellitus is associated with neonatal morbidity. It is commonly agreed that the morbidity decreases when diabetic control is tightened. The most common methods for the determination of diabetic control are the self-monitoring of blood glucose levels (SMBG) and the measurement of HbA1c-levels. SMBG is used for the observation of daily glucose levels while HbA1c-levels give information on the glycaemic control of the patients over the previous two to three months. The widely used guidelines of the American Diabetes Association recommend a minimum of three SMBG per day during pregnancy and state that in women with diabetes, HbA1c-levels within 1% above the normal range (6.0-7.0%) are acceptable during pregnancy. However, several population-based studies have shown that, despite the achievement of these treatment goals, the incidence of congenital malformations and macrosomia (birth weight >90th centile) was higher in women with type 1 diabetes compared to the reference population.

A novel device for the monitoring of glucose levels is the Continuous Glucose Monitoring System (CGMS). This device measures glucose levels in the subcutaneous interstitial tissue fluid every five minutes during three days and makes continuous ambulatory monitoring of glucose profiles throughout the pregnancy possible.

We used the CGMS to observe diurnal glucose profiles in pregnant women with type 1 diabetes and to assess the relation between these glucose profiles and perinatal outcome.

First, we determined the accuracy and reproducibility of the CGMS in pregnant women with type 1 diabetes and concluded that these are adequate. Secondly, the definition of normoglycaemia during pregnancy was established by the use of the CGMS in healthy pregnant volunteers. We concluded that the incidental fall of glucose values below the lower limit of normoglycaemia, especially during the night, and glucose values that exceed the upper limit of normoglycaemia, especially after breakfast in the third trimester, appear to be a normal phenomenon in healthy women.

The use of the CGMS in fifty pregnant women with type 1 diabetes led to the following findings and conclusions:

HbA1c-levels in pregnant women with type 1 diabetes do not adequately reflect the complexities of glycaemic control and HbA1c-levels between 6.0 and 7.0% are not 'safe' during pregnancy. Treatment in these women should be aimed at achieving normal HbA1c-levels.

Frequent SMBG rather than HbA1c-levels should be the main indicators of diabetic control on which treatment strategies are based and should be performed at least ten times a day. Day-to-day glucose variability is a major obstacle in the treatment of pregnant women with diabetes and obstructs adequate fine-tuning of insulin regimens in about half the patients.

Sibling birth weight is a better predictor of macrosomia than HbA1c-levels.

Women with type 1 diabetes who give birth to a severely macrosomic infant have higher glucose levels during the second trimester of pregnancy than women with diabetes who give birth to a normal weight infant. Tight glycaemic control, especially during the second trimester of pregnancy, seems of great importance for the prevention of severe macrosomia.