SAN DIEGO (FRONTLINE MEDICAL NEWS)– Early treatment of pregnant women with prediabetes led to lower hemoglobin A1C (HbA1C) levels during the second trimester and at delivery in a randomized, controlled trial.
Study subjects were 83 women with a first trimester HbA1C of 5.7%-6.4% (median of 5.8%) indicative of prediabetes. HbA1C levels during the second trimester were 5.2% and 5.3% in the 42 women who were randomized to receive early treatment and in the 41 who received routine care, respectively, and the levels at delivery were 5.5% and 5.8%, respectively, Dr. Sarah Osmundson reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
The overall rate of positive glucose tolerance tests (GTT) or insulin use prior to the GTT – the primary study outcome – did not differ significantly between the groups but did trend toward lower in the early treatment group (45.2% vs. 55%; relative risk, 0.82), said Dr. Osmundson of Stanford (Calif.) University.
Further, although no difference was seen in the rate of gestational diabetes mellitus (GDM) among women with prepregnancy obesity in the early treatment and routine care groups, early treatment was associated with a 50% lower rate of GDM in nonobese women (29.6% vs. 59.1%, relative risk, 0.50), she said.
The participants had a singleton pregnancy, no chronic steroid use, and no preexisting diabetes. They were enrolled between May 2012 and June 2014, and all met with a certified diabetes educator at study entry to discuss healthy weight gain strategies in pregnancy and to set personalized weight gain goals.
Those in the early treatment group also were counseled to keep a diary to track food intake, were advised to monitor portion size, and limit carbohydrate intake to no more than 45% of total diet, and were seen by a dietitian or obstetrician every 2 weeks. They self-monitored blood glucose levels four times daily, and insulin was initiated if more than 20% of values were elevated.
The routine care group received usual prenatal care, including a visit with a provider every 4 weeks.
Patients in both groups underwent an oral GTT between 26 and 28 weeks of gestation.
Patients in the early treatment group with a positive GTT continued treatment, and those with a negative GTT continued treatment, but reduced monitoring to twice daily – returning to four times daily testing if levels increased. Those in the routine care group initiated treatment if the GTT was positive, and continued usual care if it was negative.
The groups gained a similar amount of weight during the study and did not differ in terms of insulin use, but the early treatment group started insulin at an earlier gestational age, and nonsignificant trends were seen toward a decrease in the primary outcome and toward lower GTT values in that group. The early treatment group patients also had a lower cesarean delivery rate (29.4% vs. 47,2%; RR, 0.63), but the difference did not reach statistical significance, Dr. Osmundson said.
Similarly, nonsignificant trends were seen toward lower infant birth weight, less macrosomia, and lower umbilical cord C-peptide levels in the early treatment group.
Glycosylated HbA1C is widely used for monitoring glycemic control, but was only recently adopted as an additional method of screening for diabetes. The measure has several advantages over the oral GTT, as it can be performed in a nonfasting state, requires only one blood draw, and provides information about average glucose exposure over time, she said.
The American Diabetes Association accepted HbA1C as an additional method for diagnosing type 2 diabetes in 2009, and classified those with levels between 5.7% and 6.4% as having prediabetes. That same year, an International Association of Diabetes in Pregnancy study group recommended that HbA1C of 6.5% or greater in pregnancy be considered overt diabetes, but made no recommendations regarding the management of those with prediabetic HbA1C, Dr. Osmundson said.
Prediabetes predicts a 50% cumulative incidence of type 2 diabetes within 5 years in nonpregnant patients, but much less is known about the condition in pregnant women, she added, noting that recent studies suggest a threefold increased risk for gestational diabetes in the second trimester – and perhaps even greater risk in obese women – among those with prediabetes.
The addition of HbA1C to the prenatal panel in California, along with a recommendation that those with prediabetes be diagnosed with and treated for gestational diabetes, provided the opportunity to evaluate whether such treatment affected the incidence of gestational diabetes as compared with usual care, she noted.
“We hypothesized that treatment would lower the risk of GDM, especially among obese women,” she said.
Though limited by the sample size and the fact that providers were not blinded to patients’ treatment group, the randomized, controlled study design is a strength, and the findings add to the limited data on HbA1C in pregnancy and the management of prediabetes in pregnant patients, she said.
The study was underpowered to determine whether early treatment reduces the risk of GDM in women with prediabetes, but the findings suggest that such treatment may reduce the risk among nonobese women.
“While this finding is unexpected, we think the findings are consistent with literature suggesting that women with prepregnancy obesity remain at higher risk of adverse perinatal outcomes even in absence of GDM or excessive weight gain. We hypothesize that any small effect may be attenuated by the morbidity associated with prepregnancy adiposity. Larger studies powered to examine the primary outcomes and perinatal outcomes are required,” she concluded.
This study was funded by the American College of Obstetricians and Gynecologists Abbott Nutrition Research Fellowship, the Stanford Child Health Institute, and the Valley Foundation for the California Institute of Medical Research. Dr. Osmundson reported having no disclosures.
