Women with history of gestational diabetes at risk for diabetes years after pregnancy

Lifestyle intervention and metformin were effective in delaying or preventing diabetes.

Progression to diabetes was more common in women with a history of gestational diabetes compared with those without a history of disease despite a similar degree of glucose intolerance.

Researchers examined the differences between women enrolled in the Diabetes Prevention Program with and without a history of gestational diabetes. They randomly assigned 2,190 women to the Diabetes Prevention Program; 350 women reported a past history of disease and 1,416 women reported no history of disease. Participants were assigned to receive placebo, metformin or intensive lifestyle intervention.

Reduced incidence

Women with a history of gestational diabetes in the placebo group had an incidence rate of diabetes 71% higher than that of women without disease history.

“The risk for developing diabetes following an episode of gestational diabetes mellitus probably persists over a lifetime, as our women were almost 12 years postpartum at the time of entry into the study,” Robert E. Ratner, MD, vice president for Scientific Affairs, MedStar Research Institute in Hyattsville, Md., told Endocrine Today.

“Therefore, the need to screen and intervene in these women cannot stop after the six-week or one-year visit,” he said.

In women with a history of gestational diabetes, metformin therapy reduced the incidence of diabetes by 50% (P=.006) compared with placebo. Intensive lifestyle reduced the incidence of diabetes by 53% (P=.002) compared with the placebo group, according to the study.

In parous women without a history of gestational diabetes, there was a 49% risk reduction in the intensive lifestyle group compared with the placebo group (P<.001) and a 41% risk reduction compared with the metformin group (P=.001). Metformin showed a 14% reduction when compared with placebo.

Metformin may be more effective in women with a history of gestational diabetes mellitus compared with those without a history of disease, according to the study.

“Women with a history of gestational diabetes mellitus who currently have impaired glucose tolerance remain at an increased risk for developing diabetes years after the index pregnancy and appear to benefit from either lifestyle or pharmacologic interventions,” they wrote. – by Christen Haigh

J Clin Endocrinol Metab. 2008;93:4774-4779.

Many clinicians do not recognize just how many women with a past history of gestational diabetes go on to develop frank glucose intolerance. This is an important study because the results offer ways to reduce the incidence of subsequent diabetes in these women.

– Robert W. Rebar, MD

Endocrine Today Editorial Board member

The findings are interesting, although a bit perplexing, since I am unaware of a biological reason for more rapid progression to type 2 diabetes from gestational diabetes mellitus and impaired glucose tolerance than from impaired glucose tolerance alone or for better apparent protection from diabetes with metformin and relatively poor protection with lifestyle in women with a history of gestational diabetes. It is important to keep in mind that gestational diabetes was self reported and that the women who gave a history of gestational diabetes were younger and closer to pregnancy than those who did not, so there could easily be an ascertainment bias with regard to who really did have gestational diabetes. The age difference could also have contributed to the apparently good response to metformin (recall that metformin worked better in relatively young individuals in the Diabetes Prevention Program cohort overall).

These things said, the results are clearly consistent with current recommendations to evaluate women with prior gestational diabetes early and often to see if they are developing impaired glucose levels or diabetes. The apparent poor response to intensive lifestyle modification is disappointing, but given the post-hoc nature of the analysis, this should not discourage the use of weight loss and exercise in women with prior gestational diabetes — at least until there are some more definitive data about whether or not it works. The results also suggest that gestational diabetes should be added to the list (eg, the one provided by the ADA) of specific characteristics to consider when deciding about using metformin for diabetes prevention. But again, more definitive results would be useful in that regard.

– Thomas A. Buchanan, MD

Professor, University of Southern California, Los Angeles