The goals of monitoring and treatment are very different. We monitor in order to guide treatment, to guide further diagnostic testing, to predict outcome, and to understand pathophysiology. But when we consider the value of glucose sensors and insulin pumps, we really need to consider the goals of treatment, which include reducing hyperglycemia without tripping over the threshold into hypoglycemia, and reducing short- and long-term neonatal and maternal complications of diabetes.
Dr. C. Andrew Combs
We have little data to guide us. A 2007 meta-analysis of randomized controlled trials comparing continuous subcutaneous insulin infusion (CSII) to multiple daily injections (MDI) in pregnant patients – an analysis separate from the Cochrane systematic review of 2007 that Dr. Moore mentions – found no significant differences in glycemic control or pregnancy outcomes. The studies included were published between 1986 and 1993, and since then, there have been no randomized trials comparing CSII and MDI in pregnant women (Am. J. Obstet. Gynecol. 2007;197:447-56).
With respect to CGM, a study reported by Dr. Y. Yogev and his associates in 2003 showed some promise: It compared the daily glycemic profiles reflected by continuous and intermittent blood glucose monitoring in pregnant women with type 1 diabetes, and found that CGM recorded high postprandial blood glucose levels and nocturnal hypoglycemic events that were unrecognized by intermittent monitoring. The question remains, however, whether such information leads to clinical interventions that can improve outcomes (Obstet. Gynecol. 2003;101:633-8).
A study published a year later, also by Dr. Yogev, showed that asymptomatic hypoglycemic events were surprisingly common in insulin- and glyburide-treated patients with gestational diabetes mellitus. The findings were eye-opening, but we really don’t know the significance of such hypoglycemic events.
We take it as a matter of faith that it’s bad to be hypoglycemic. In reality we know very little about what’s "normal" and "abnormal" in diabetic pregnant women and nondiabetic pregnant women.
In the only randomized controlled trial of CGM during pregnancy, women with type 1 and type 2 diabetes who were early in their pregnancies were assigned to perform self–blood glucose monitoring seven times a day or to have professional CGM for 1-week periods every 4-6 weeks. Findings in both groups were used to adjust therapy. By 36 weeks’ gestation, the CGM group had significantly lower HbA1c. Birth weights and the rate of macrosomia also were reduced (BMJ 2008;337:a1680).
The findings were impressive, but some of the data are unusual. For instance, the incidence of large-for-gestational-age (LGA) infants was reduced from 60% to 35%; both of these rates are high compared with rates at other centers. Data from the California Sweet Success program – a statewide effort to collect and share data on diabetes in pregnancy – show LGA in patients with type 1, type 2, and gestational diabetes to be 22.5%, 20%, and 11.4%, respectively – 27% of the type 1 patients were on CSII.
The American Association of Clinical Endocrinologists last year published a consensus statement recommending CGM for patients with type 1 diabetes who have certain risk factors, like frequent hypoglycemia or HbA1c over target. The AACE statement also includes those who are pregnant or about to become pregnant as ideal candidates for CGM, but curiously it provides no data to support this.
We have much more to learn. It is telling that in a recently published evaluation of a closed-loop insulin delivery model (an "artificial pancreas") in pregnant women with type 1 diabetes, investigators concluded that "before outpatient closed-loop studies proceed, they must be supported by scientifically rigorous data on safety and efficacy of real-time CGM," as well as more data on the algorithm for adjusting insulin infusion rates based on glycemic levels seen in pregnancy.
Dr. Combs is with Obstetrix Medical Group in San Jose, Calif. He said he had no relevant financial disclosures.
This feature is based on presentations given by Dr. Moore and Dr. Combs at the annual meeting of the Diabetes in Pregnancy Study Group of North America in Washington, D.C.