News: Should you treat mild gestational diabetes?

July 1, 2008

When it comes to hyperglycemia in pregnancy, no clear blood glucose thresholds exist to determine when your patient is at risk for adverse outcomes.

When it comes to hyperglycemia in pregnancy, no clear blood glucose thresholds exist to determine when your patient is at risk for adverse outcomes, according to the results of a large, international study.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study included more than 23,000 women from nine countries with glucose values of less than 200 mg per dL 2 hours after a 75-g glucose load. Those with values of 140 to 200 mg per dL met World Health Organization criteria for the diagnosis of gestational diabetes mellitus (GDM).

The researchers calculated the adjusted odds ratios (OR) for adverse pregnancy outcomes associated with an increase in the fasting plasma glucose level of 1 SD (6.9 mg per dL [0.4 mmol per L]), an increase in the 1-hour plasma glucose level of 1 SD (30.9 mg per dL [1.7 mmol per L]), and an increase in the 2-hour plasma glucose level of 1 SD (23.5 mg per dL [1.3 mmol per L]).

The authors of an accompanying editorial point out that the outcome that was most closely linked to maternal carbohydrate intolerance was cord-blood C-peptide levels, a surrogate marker that by itself is generally not of major clinical concern. In contrast, the outcome of greatest concern, CD, was only moderately affected by increased maternal glucose levels.

Nevertheless, the authors conclude that the "significant associations between adverse outcomes and higher levels of maternal glucose within what is currently considered a nondiabetic range" mandate reconsideration of current guidelines for diagnosing and treating gestational hyperglycemia.

A RELATED STUDY in the same issue of the NEJM reports that metformin, alone or with supplemental insulin, is preferable to insulin alone for GDM because it rates higher in patient acceptability without increasing neonatal complications.

Researchers from New Zealand and Australia randomly assigned 751 women with GDM at 20 to 33 weeks' gestation to either metformin (with supplemental insulin if necessary) or insulin.

The rate of neonatal complications (consisting of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score less than 7, and prematurity) was virtually identical: 32% for the metformin group, and 32.2% for the insulin group. However, almost three times as many women receiving metformin as those receiving insulin would choose to receive their assigned treatment again (76.6% vs. 27.2%, P<.001). Almost half (46.3%) of the women receiving metformin also received supplemental insulin.

The question remaining, according to the authors of an accompanying editorial, is how metformin stacks up against glyburide, which has been reported to require supplemental insulin in far fewer women.

HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358:1991-2002.

Rowan JA, Hague WM, Gao W, et al. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008;358:2003-2015.

Ecker JL, Greene MF. Gestational diabetes––setting limits, exploring treatments. N Engl J Med. 2008;358:2061-2063.