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Continuous Glucose Control Improves Pregnancy Outcomes in Diabetes

For diabetic women, continuous glucose monitoring during pregnancy may not only improve glycemic control but also diminish the risk of complications, researchers found.

Diabetic women on continuous glucose monitoring as part of antenatal care had 64% lower relative risk of macrosomia and 0.6% lower absolute glycosylated hemoglobin levels compared with standard care, reported Helen R. Murphy, M.D., of Ipswich Hospital.

This intervention is one of the few ever shown to lower rates of large-for-gestational-age birth weight, which, although one of the most common complications of pregnancy in diabetes, has proven resistant to even optimal glycemic control and insulin pump therapy.

Macrosomia increases the risk of labor complications, Cesarean delivery, intracranial hemorrhage, shoulder dystocia, and respiratory distress. Accumulating evidence suggests longer-term health risks of insulin resistance, obesity, and type 2 diabetes as well.

Preventive strategies like continuous glucose monitoring are valuable given these lasting effects, commented Mario R. Festin, M.D., of the University of the Philippines in Manila, in an accompanying editorial. "Continuous glucose monitoring is relatively cheap compared with a clinic-based monitoring system, and more widespread use may lower costs and make it affordable even in developing countries," he wrote.

The American Diabetes Association recommends glucose self monitoring glucose at least three times a day. The American Academy of Family Physicians recommends that measurement at least four times daily.

The prospective trial included 71 women with type 1 or 2 diabetes seen for standard antenatal care at two secondary-care multidisciplinary obstetric clinics for diabetes. The women were randomized to open-label treatment including standard finger-prick glucose monitoring alone or with continuous glucose monitoring.

Continuous monitoring was done for five to seven days at four- to six-week intervals during pregnancy until 32 weeks gestation, since continuous glucose monitoring is more uncomfortable later in pregnancy, the researchers said.

Glucose measurements were used as an educational tool and to make therapeutic adjustments to diet, exercise, and insulin regimens. Longer-range glycemic control as measured by glycosylated hemoglobin (HbA1c) improved during treatment with differences between groups that emerged later in pregnancy. Mean HbA1c levels dropped from 7.3% at enrollment to 6.1% in the continuous glucose monitoring group and 6.4% in the control group at 28 to 32 weeks gestation (P=0.1).

Levels dropped further at 32 to 36 weeks gestation with continuous glucose monitoring to reach a significant difference between groups (5.8% versus 6.4%, P=0.007).

The HbA1c levels may not have shown benefits until the third trimester because of the slow clearance of glycosylated hemoglobin from the circulation as well as the learning curve for women and health professionals using continuous monitoring devices, the researchers said.

"Initiating continuous glucose monitoring earlier in pregnancy -- ideally before conception -- may help to achieve an earlier impact on glycemic control," they recommended. The effect on glucose control appeared to reduce mean birth weights as well.

The average birth weight for infants of mothers on continuous glucose monitoring was in the 69th percentile whereas it was in the 93rd percentile for gestational age and gender for those in the control group (P=0.02).

Macrosomia -- birth weight in the 90th percentile or above -- was significantly less common in the intervention group (35% versus 60%, odds ratio 0.36, P=0.05). Infants classified as extremely large for gestational age -- 97.7th percentile or above -- tended to be less likely in the continuous glucose control group as well as compared with standard antenatal care (13.5% versus 30%, P=0.13).
Risk of Cesarean delivery was similar between groups, although the intervention tended to reduce emergency operative deliveries (P=0.08).

The intervention may have had an effect by motivating women to reduce glucose excursions, particularly postprandial excursions, they speculated.

"The visual impact of continuous glucose monitoring rapidly focused clinical input towards reducing hyperglycemic spikes," they wrote, "which are less apparent from a patient diary or glucose meter download but essential if seeking to limit the transfer of glucose to a fetus."

The authors pointed out that "although rates of macrosomia were reduced in women using continuous glucose monitoring, they remain 3.5 times higher than in the general maternity population."

So, they said, although continuous glucose monitoring helps improve average glycemic control, it's "still inadequate for achieving optimal day to day glucose control and birth weights comparable with the background population."
Murphy HR, et al "Effectiveness of continuous glucose monitoring in pregnant women with diabetes: randomized clinical trial" BMJ 2008; 337: a1680. Festin MR "Continuous glucose monitoring in women with diabetes during pregnancy" BMJ 2008; 337: a1472.
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