Balancing Weight and Glucose in Gestational Diabetes Mellitus

The instinctive concern of a pregnant woman for her baby creates a receptive environment for advice, and so it is particularly important that medical recommendations during pregnancy should be factual and reasoned. In this issue ofDiabetes Care, Black et al. (1) have shown in a group of women who did not have gestational diabetes mellitus (GDM) by traditional thresholds that maternal overweight and obesity accounted for 21.6% of large-for-gestational-age (LGA) infants, and when GDM as defined by the newer American Diabetes Association (ADA) criteria was added into the equation, the combination was responsible for 23.3% of neonatal LGA. This article is a helpful addition to the debate balancing the impact of maternal adiposity or hyperglycemia on the risk of LGA in the baby. The historical poor outcomes of pregestational diabetes are testimony to the harmful effects of high glucose in early pregnancy as manifest by congenital malformations and in later pregnancy as evidenced by LGA and its consequences. Interestingly, over time with better glucose control the risk for congenital malformations has decreased but not the risk for LGA (2). A proportion of women with no known diabetes have a pancreas that cannot respond to the increased insulin requirements of pregnancy, and they therefore develop GDM. These women have more LGA and shoulder dystocia (3), and there is good evidence that treatment reduces these problems (4). Overweight mothers also have less favorable outcomes. In population studies, obesity is associated with more LGA, gestational hypertension, preeclampsia, GDM, and extra pounds retained postpartum, whereas excess weight gain during pregnancy is more closely associated with preeclampsia, LGA, and retained weight postpartum (5–7). Women who have bariatric surgery have less LGA infants on subsequent pregnancies, indicating a role for obesity (8). The prospective study of Vinter et al. (9) using nutrition counseling and physical activity in obese pregnant women showed that less weight gain could be achieved but the maternal outcomes (including the risk of GDM) were similar in control and intervention groups, and the birth weights were not significantly different. In fact, the intervention group babies were slightly heavier at 3,742 vs. 3,593 g. Recent meta-analyses showed similar patterns: weight gain in pregnancy can be attenuated by intervention, but birth weight is unchanged (10–12). Both hyperglycemia and maternal adiposity increase the risk of LGA. Teasing out the relative importance of these components is a challenge. An analysis of the HAPO (Hyperglycemia and Adverse Pregnancy Outcome) observational data by Catalano et al. (13) showed increased adjusted odds ratios (ORs) for LGA derived from maternal GDM as defined by IADPSG (International Association of the Diabetes and Pregnancy Study Groups) criteria (OR 2.58) and maternal obesity (OR 2.07), and these were additive when both risk factors were present (OR 5.35). Prospective studies have indicated that obesity may be more important in driving LGA (14,15)—perhaps mediated by increased lipids (16). The article of Black et al. is a retrospective analysis of the records of 9,835 women, all of whom had a 75-g oral glucose tolerance test, and excludes those meeting criteria for GDM used in 2005– 2010 (1). In this group of women, 60% were overweight and 19% had GDM by IADPSG criteria, and of these 76% were obese. The obese GDM women had a 5.5-fold increased risk of LGA, whereas obesity alone or GDM alone had a 1.7or 2.0-fold increased risk of LGA, respectively, similar to the HAPO report (13). Overall however, obesity and overweight accounted for 21.6% of LGA, and when GDM was added to obesity or overweight the combination accounted for a total of 23.3% of LGA. Only in this combined group was birth trauma increased, but this did not reach statistical significance. A recent article by Retnakaran et al. (17) showed similar results, with maternal weight and weight gain but not glucose being predictors of LGA, and these metabolic factors only accounted for 26% of LGA. Thus in study populations that include women diagnosed as GDM by the new ADA criteria obesity appears to play amore important role in determining LGA but, all told, three-quarters of LGA remains unexplained bymaternal obesity, weight gain, or glucose. This leaves us with some quandaries: 1) What can we do to lessen LGA, 2) where do we draw the line to diagnose GDM, and 3) what is the real cause of most cases of LGA? Treating hyperglycemia in pregnancy will reduce LGA, and therapy is straightforward. If nutrition/lifestyle intervention is not successful, then insulin or oral hypoglycemic agents can be used. While on a diet, excess weight gain may be attenuated, but with the addition of insulin or sulfonylurea increased weight gain often ensues, perhaps negating some of the benefits of controlling glycemia. Pursuing diet/activity for longer may be advantageous if the elevation of glucose is mild, rather than rushing into therapy with insulin. In obese women, dieting will reduce weight gain and benefit the mother with less preeclampsia, postpartum weight retention, and perhaps GDM, but the evidence for decreasing LGA is not there at present. It may be that as Symonds et al. (18) suggested, food restriction in early pregnancy can actually be a stimulus for more white adipose tissue accumulation in the fetus, and it is of note that nearly all of the dietary intervention studies started before 20 weeks’ gestation. Maybe more advantageous would be public awareness of the adverse consequences of obesity for the baby so that the mother’s starting body weight might be lowered. Society has successfully got themessage out about smoking and alcohol in pregnancy; obesity and pregnancy weight gain should now be the next targets. The diagnosis of GDM remains controversial, and there is a National Institutes of Health (NIH) Consensus Conference to examine the issue inMarch. The new ADA criteria will diagnose between 9–25% of the pregnant population with a disease (19), have major implications for the mother in terms of glucose monitoring, may involve diabetes medications, will mean more obstetrical monitoring and