Physiologic subtyping may help focus care for women with gestational glucose intolerance

Pregnant women with insulin-resistant gestational glucose intolerance face risks for adverse outcomes, but physiologic subtyping can help tailor interventions, according to researchers.

In a hospital-based cohort study, Daryl J. Selen, MD, of Massachusetts General Hospital (MGH), and colleagues assessed 236 women with gestational glucose intolerance (GGI) and 1,472 women with normal glucose tolerance (NGT) enrolled in the MGH Obstetrical Maternal Study between 1998 and 2006.

The researchers compared the odds of adverse outcomes, including large for gestational age (LGA) birthweight, neonatal intensive care unit (NICU) admission, pregnancy-related hypertension and cesarean delivery among women with and without normal glucose tolerance.

Women with gestational diabetes mellitus (GDM) and their infants have an increased risk for these adverse outcomes. Women with GGI who have an abnormal initial screening glucose loading test (GLT) also have an increased risk for these outcomes, whether they meet GDM diagnostic criteria or not, the researchers said.

The researchers defined physiologic subtypes of GGI — including all women who had an abnormal initial GDM screening test — and delineated the subtypes by insulin resistance, insulin deficiency or mixed pathophysiology using a homeostasis model assessment.

Hypothesizing that women with the insulin-resistant GGI subtype would be at highest risk, the researchers sought to determine if GGI subtypes are at differential risk for adverse pregnancy outcomes.

According to the study, 49% (n = 115) of the women with GGI had insulin-resistant GGI, 27% (n = 70) had insulin-deficient GGI, 17% (n = 40) had mixed pathophysiology and 5% (n = 11) were uncategorized. Also, 12% (n = 28) were diagnosed with GDM.

The women in the insulin-deficient and mixed-pathophysiology subtypes were older than the women in the NGT group. Also, the women with insulin-resistant GGI were more likely to have a BMI equal to or greater than 30 kg/m² compared with the NGT group, but women with insulin-deficient GGI were more likely to have a BMI less than 25 kg/m².

While there were no statistically significant differences in insurance status between the subtypes, women with insulin-resistant GGI were less likely to be married than women in the NGT group. Women with insulin-resistant GGI were more likely to identify as Latina as well.

Compared with women with NGT, women who were insulin resistant had higher fasting insulin and women who were insulin deficient had lower fasting insulin. Also, women who were insulin resistant and who had mixed pathophysiology had higher fasting glucose than women with NGT, though women with NGT and women who were insulin deficient had similar fasting glucose.

The researchers defined LGA birthweight as greater than the 90th percentile for gestational age. Women with insulin-resistant GGI had a 19% rate of LGA birthweight, women who were insulin deficient had a 14% rate, women with mixed pathophysiology had a 13% rate and women with NGT had a 9% rate.

Also, women in the insulin-resistant and mixed-pathophysiology subtypes saw significantly higher birthweight percentile results compared with the women with NGT, but these effects were attenuated and no longer statistically significant in the adjusted models.

Women with insulin-resistant GGI saw the highest incidence of NICU admission, followed by women with mixed pathophysiology GGI and insulin-deficient GGI, compared with the NGT group. Further, the researchers noted a trend toward increased odds of NICU admission in the infants of women with insulin-resistant GGI, compared with the NGT group.

Finally, 24% of women with insulin-resistant GGI, 18% of women with mixed pathophysiology, 14% of the NGT group and 13% of women with insulin-deficient GGI had increased incidence of pregnancy-related hypertension.

The researchers concluded that insulin resistance appears to convey the highest risk for adverse pregnancy outcomes among women with GGI, adding that their findings provide the premise for future studies of increasing monitoring or treatment of these patients.