Gestational diabetes: an opportunity for improvement.

Pregnancy has long been recognized as a state of relative insulin resistance, and those women who cannot meet the increased demands for insulin during pregnancy have been labeled as having gestational diabetes mellitus (GDM). What threshold should be used in defining GDM (1) and the benefits of (2) and best methods for treating GDM (3, 4) continue to be matters of ongoing investigation and debate. There should be no debate, however, about the relationship between GDM and later diabetes mellitus (DM). Indeed the pioneering work by O’Sullivan and Mahan (5) in the 1960s focused on pregnancy as a stress test for the pancreas that identified women at significant risk for future DM. Results of the Diabetes Prevention Program (DPP) published in this issue of JCEM now argue that identifying GDM offers not just a warning for future DM but also an important opportunity to intervene and prevent incident cases (6). DPP randomized over 3000 individuals with impaired glucose tolerance (IGT), including women identified with IGT as a result of a history of GDM, to treatment with metformin, intensive lifestyle (ILS), or placebo and subsequently evaluated those enrolled semiannually to determine who developed DM. The DPP investigators have previously reported that in the overall cohort, both ILS and metformin reduced the incidence of diabetes by 58 and 31%, respectively, compared with placebo. Their current analysis focuses on women in DPP who reported a history of GDM and compares their outcomes to those of parous women who reported no such history. The results emphasize the risk GDM confers for future DM but, happily given this risk, also argue that women with GDM are more likely to benefit from pharmacological intervention. Among those in the placebo arm, 38% of women with a history of GDM developed DM in the 3 yr after randomization, an alarming rate of progression that echoes many past studies. Moreover, women with a history of GDM were at a 71% increased risk for developing DM compared with other parous subjects, an increase that is remarkable given that all, by definition, had demonstrated IGT and similar glucose levels at entry into DPP. Women with and without a history of GDM benefited similarly from ILS, demonstrating an approximately 50% reduction in risk of progression. Yet, whereas parous women without a history of GDM who were randomized to metformin treatment demonstrated a nonsignificant 14% reduction in progression, the benefits of metformin in the group with a history of GDM matched that of ILS: women with IGT and a history of GDM who were treated with medication were 50% less likely to progress to DM than those with an equivalent history in the placebo group. The investigators estimate that only five to six women with IGT and a history of GDM would need to be treated over 3 yr with either metformin or lifestyle changes to prevent one case of DM. In summary, this report emphasizes what previous DPP results argued: women with IGT after GDM should be encouraged to follow a plan of lifestyle modification or begin metformin treatment. In choosing between these alternatives, some may question whether pharmacological intervention truly prevents DM or simply restores euglycemia in those with preclinical disease. Further follow-up of those treated with metformin may be useful in answering this question, but, in the meantime, normalizing values on glucose testing seems a reasonable and reasonably important surrogate outcome. Because metformin is generally well tolerated, such therapy seems an appropriate alternative to use in treating women with IGT and a history of GDM. Given the time that had elapsed from the identification of GDM until enrollment in DPP, details about the diagnosis and management of GDM were not available. Accordingly, the investigators could not confirm the diagnosis or identify whether further variables—specific results from glucose tolerance testing in pregnancy, need for insulin, fetal macrosomia—could identify those cases at greatest risk. Nor for that matter, were they able to say whether similar variables in the parous controls might be similarly useful. One other important limitation is that because DPP required those enrolled to have identified IGT, the question