Correspondence
Treatment for Mild Gestational Diabetes
N Engl J Med 2010; 362:365-367January 28, 2010
- Article
To the Editor:
The trial of treatment of mild gestational diabetes mellitus showed no difference in primary outcomes (Oct. 1 issue).1 However, the rate of fetal overgrowth was lower in the treatment group (7.1%) than in the control group (14.5%). Reductions in secondary outcomes (cesarean deliveries, shoulder dystocia, preeclampsia) in the treatment group were significant. Among mothers in both groups the mean body-mass index (BMI, calculated as the weight in kilograms divided by the square of the height in meters) exceeded 30, and the women in the treatment group (who received formal nutritional counseling and diet therapy) showed significantly less weight gain than those in the control group.
The adverse effects of fetal overgrowth have been recognized in many studies of overweight and obese women.2-4 The benefits attributed to the management of mild gestational diabetes mellitus probably resulted from limiting gestational weight gain. Excess maternal weight contributes to the birth of more than four times as many infants who are large for their gestational age than does diabetes.5 The current preoccupation with ever more minor derangements in the results of glucose-tolerance tests combined with a failure to address maternal overweight and obesity as dominant drivers of fetal and neonatal morbidity comes at enormous cost. We should concentrate resources on weight control rather than glucose levels to do the maximum good in pregnancy, as Odent suggests.6
Barry N.J. Walters, F.R.A.C.P., F.R.A.N.Z.C.O.G.
University of Western Australia, Perth, WA, Australia
banjow@iinet.net. au No potential conflict of interest relevant to this letter was reported.
6 References1
Landon MB ,Spong CY ,Thom E , et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009;361:1339-1348
Full Text | Web of Science | Medline2
Stotland NE ,Cheng YW ,Hopkins LM ,Caughey AB . Gestational weight gain and adverse neonatal outcome among term infants. Obstet Gynecol 2006;108:635-643
CrossRef | Web of Science | Medline3
Nohr EA ,Vaeth M ,Baker JL ,Sorensen TIA ,Olsen J ,Rasmussen KM . Combined associations of prepregnancy body mass index and gestational weight gain with the outcome of pregnancy. Am J Clin Nutr 2008;87:1750-1759
Web of Science | Medline4
Cedergren M . Effects of gestational weight gain and body mass index on obstetric outcome in Sweden. Int J Gynaecol Obstet 2006;93:269-274
CrossRef | Web of Science | Medline5
Catalano PM ,Ehrenberg HM . The short- and long-term implications of maternal obesity on the mother and her offspring. BJOG 2006;113:1126-1133
CrossRef | Web of Science | Medline6
Odent M . Gestational diabetes and health promotion. Lancet 2009;374:684-684
CrossRef | Web of Science | Medline
To the Editor:
To minimize what Landon et al. referred to as a “limitation” in earlier studies of the treatment of gestational diabetes mellitus, the investigators chose not to inform the women in the control group (or their caregivers) of the results of oral glucose-tolerance tests. This approach limited out-of-study treatment of diabetes in these women.
The decision to perform a placebo-controlled trial requires “clinical equipoise.”1 In the current report, women in the control group gained more weight, had more hypertension and preeclampsia, and were more likely to require cesarean delivery. Their infants had significant levels of excess weight gain and shoulder dystocia, and greater (although not significant) levels of excess preterm deliveries, admissions to neonatal intensive care units, requirements for intravenous glucose, respiratory distress syndrome, and nonspecified birth trauma.
Although the study may encourage physicians to use approaches to treatment that we have advocated for several decades, we question whether it was worth exposing the control group to harm. We comment on these issues in a special set of articles in the Journal of Diabetes. 2-4
Zachary Bloomgarden, M.D.
Mount Sinai School of Medicine, New York, NY
zbloom@gmail.com Lance Stell, Ph.D.
Carolinas Medical Center, Concord, NCLois Jovanovic, M.D.
Sansum Diabetes Research Institute, Santa Barbara, CANo potential conflict of interest relevant to this letter was reported.
4 References1
Gifford F . Clinical equipoise and the uncertainty principles both require further scrutiny. BMJ 2001;322:795-795
CrossRef | Web of Science | Medline2
Bloomgarden ZT. Troubling issues raised by gestational diabetes trial. J Diabetes 2009 October 14 (Epub ahead of print).
3
Stell LK. Conflict of interest in diabetes research. J Diabetes 2009 October 14 (Epub ahead of print).
4
Jovanovic L. Rationale for the treatment of mild hyperglycemia during pregnancy. J Diabetes 2009 October 14 (Epub ahead of print).
Author/Editor Response
Walters suggests that the observed benefits of treating mild gestational diabetes mellitus may have resulted from simply limiting excess maternal weight gain and that treating “minor” degrees of hyperglycemia during pregnancy may be of limited value. We conducted a secondary analysis, which suggests that specific treatment for gestational diabetes may have benefits that are independent from those of reduced maternal weight gain. In one analysis (unpublished data), the frequency of large-for-gestational-age infants in women with excessive weight gain1 was 9.2% in women who were treated for gestational diabetes as compared with 20.8% in untreated women. Furthermore, in a study of overweight, nonobese pregnant women (BMI, 25.0 to 29.9), 7% of those in the group receiving treatment for gestational diabetes had large-for-gestational-age infants as compared with 12% of those in the control group (unpublished data). Thus, it appears to be inadvisable to focus solely on the nutritional management of obese gravidae or to neglect hyperglycemia during pregnancy in nonobese women.
Bloomgarden and colleagues suggest that we violated the principle of “clinical equipoise.” Their apparently long-established certainty concerning management of mild gestational diabetes is not in keeping with the prevailing evidence-based assessment of the value of screening for and treating gestational diabetes. The U.S. Preventive Services Task Force recently concluded that current evidence was insufficient to assess the balance of benefit versus harm with respect to the treatment of gestational diabetes.2 This alone is prima facie evidence that a stance of clinical equipoise was reasonable. The suggestion that there is near-absolute certainty concerning the benefit of treating mild gestational diabetes would have ethically precluded not only our trial but also the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) and the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study.3,4 Fifteen institutional review boards approved our protocol, and none rejected the trial on ethical grounds. In addition, an independent data and safety monitoring committee regularly reviewed the trial. Some participants would not even have met the criteria for gestational diabetes (more evidence of clinical equipoise). We strongly disagree with an assertion that we unnecessarily exposed participants to harm. Randomized trials are necessary provided that there is sufficient uncertainty and that the results will resolve the dispute among physicians, which was the case for the treatment of mild gestational diabetes.5 We agree that our results may encourage previously reluctant physicians to treat gestational diabetes, but such treatment is now supported by evidence from a clinical trial rather than by expert opinion alone.
Mark B. Landon, M.D.
Ohio State University College of Medicine, Columbus, OHCatherine Y. Spong, M.D.
Eunice Kennedy Shriver National Institute of Child Health, and Human Development, Bethesda, MDElizabeth Thom, Ph.D.
George Washington University, Washington, DCSince publication of their article, the authors report no further potential conflict of interest.
5 References1
Weight gain during pregnancy: reexamining the guidelines. Washington, DC: National Academies Press, 2009.
2
Screening for gestational diabetes mellitus: US. Preventive Services Task Force recommendation statement. Ann Intern Med 2008;148:759-765
Web of Science | Medline3
Crowther CA ,Hiller JE ,Moss JR ,McPhee AJ ,Jeffries WS ,Robinson JS . Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005;352:2477-2486
Full Text | Web of Science | Medline4
The HAPO Study Cooperative Research Group
Full Text | Web of Science | Medline5
Holt RIG . The Hyperglycemia and Adverse Pregnancy Outcomes trial: answers but still more questions about the management of gestational diabetes. Diabet Med 2008;25:1013-1014
CrossRef | Web of Science | Medline
