Gestational Diabetes Mellitus and Obesity

Gestational diabetes mellitus In a symposium on advances in the understanding of obesity and weight gain during pregnancy, Teresa A. Hillier (Portland, OR) discussed the implications that pregnancy weight gain in gestational diabetes mellitus (GDM) has for the fetus. Much of the discussion following her lecture and those of the other speakers concerned the May 2009 guidelines of the Institute of Medicine (IOM) for weight gain during pregnancy (www.iom.edu/ pregnancyweightgain), which suggest that recommendations to patients be based on prepregnancy BMI. For BMI levels 18.5, 18.5–24.9, 25–29.9, and 30 kg/m, weight gain ranges are suggested at 28–40, 25–35, 15–25, and 11–20 pounds, respectively, and the recommended rates of weight gain are 1–1.3, 0.8–1, 0.5–0.7, and 0.4–0.6 pounds/ week. GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Hillier noted the lack of consensus on screening and diagnostic criteria for GDM. In the U.S. two steps are used, a 1-h 50-g glucose challenge followed by a 75or 100-g oral glucose tolerance test (OGTT); outside the U.S., a 2-h 75-g OGTT is recommended. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study of providers blinded to GDM status reported correlations between fasting, 1-h, and 2-h glucose levels and adverse outcomes, including Caesarian section (1). The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) was a randomized controlled trial of 1,000 women with normal fasting glucose not having GDM by World Health Organization criteria (2-h glucose 140–199 mg/dl) assigned to treatment with dietary advice, self-monitoring, and insulin as required or to routine care (2). There was gestational weight gain of 8.1 vs. 9.8 kg, and adverse fetal outcomes occurred in 7 of 506 infants in the intervention group versus 23 of 524 infants in the routine care group; incidences of large for gestational age (LGA) status and macrosomia were reduced, and those was no increased risk of small for gestational age (SGA) status. Similar findings were reported in the National Institute of Child Health and Human Development (NICHD) maternal fetal study (3). (I have criticized what I consider lack of “clinical equipoise” in the design of this study, in which the women in the control group [and their caregivers] were deliberately not informed of the results of their OGTTs [4], despite our extensive knowledge of benefit of treatment of GDM summarized above and elsewhere [5].) Hillier also pointed out that macrosomia increases the risk of metabolic syndrome developing in the children at age 6–11 years (6). In an observational study of outcomes associated with gestational weight gain among 30,000 women with GDM, greater weight gain increased the likelihood of need for insulin, of preterm delivery, and of macrosomia, although it reduced the likelihood of low birth weight (7). When stratified by weight gain before versus after diagnosis of GDM, both were associated with an increase in the need for insulin, while preterm delivery rates increased only with weight gain that occurred prior to GDM diagnosis. Thus, weight gain prior to onset of GDM is important. (Studies presented at the ADA meeting further addressing this topic are discussed below.) Hillier described her study of 40,000 motherchild pairs, in which women with increasingly abnormal levels of glucose tolerance had greater risk of adverse outcome with greater weight gain (8). Follow-up observations of weight at age 5–7 years of 9,439 children from this study showed that abnormal maternal glucose tolerance increased the likelihood of the child’s weight being 95th percentile, suggesting GDM to be a modifiable risk factor, particularly in nonmacrosomic-atbirth children (9). Thus, excess weight gain increases LGA risk, risk of preterm delivery, and risk of childhood metabolic syndrome and obesity, and excessive maternal weight gain is a risk factor across all ranges of glucose intolerance; one cannot “just think about the glucose.” Ellen A. Nohr (Aarhus, Denmark) discussed risks associated with pregnancy weight gain in terms of outcomes for the mother and child. An issue with the IOM guidelines is the assessment of whether optimal weight gain for the infant is optimal for the mother. She addressed this in an analysis of 60,892 pregnancies in the Danish National Birth Cohort (10). Mothers were categorized by prepregnancy BMI, and gestational weight gain was subdivided at 10 kg (13%), 10 –15 kg (45%), 16–19 kg (21%), and 20 kg (21%). Outcomes studied included infants who were SGA and LGA, delivered by Caesarean section, and maternal weight retention of 5 kg 6 months postpartum. SGA risk was markedly increased with low weight gain only in the underweight group, although its frequency was somewhat greater with low gain in all baseline weight groups. LGA and Caesarean section risks showed similar patterns, occurring most often in the overweight and obese groups with greatest weight gain. The weight retention 6 months postpartum was greatest with greater pregnancy weight gain in all groups, but was of greatest consequence in those with greater baseline weight. Nohr concluded that ideal weight gain varies with baseline weight and appears to be 20 kg in underweight, 16 –19 kg in normal weight, 10–15 kg in overweight, and 10 kg in obese women. A follow-up study (11) compared findings among 27,000 primiparous and 32,000 multiparous women in the overall dataset. Among the latter, the risk of SGA was lower, perhaps justifying lower weight gain recommendations in this group of 10–15 kg for underweight, 5–9 kg for normal weight, and, perhaps, 5 kg both for overweight and obese multiparous women. “These suggestions ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●