Weight gain in women with gestational diabetes.

OBJECTIVE: To evaluate weight gain during pregnancy in women with gestational diabetes, and to determine whether there was a stronger or weaker correlation of maternal weight gain with neonatal birth weight in women with gestational diabetes as compared with a control group. METHODS: At delivery, 78 women with gestational diabetes and 312 control subjects were evaluated and classified according to pregravid weight for height (underweight, average weight, and overweight). Weight gain during pregnancy and neonatal birth weight in the women with gestational diabetes and in the control group were compared using analysis of covariance, controlling for selected covariables. A weight gain curve for each patient was generated to assess the rate of weight gain during early, middle, and late gestation. Linear regression analysis was used to correlate maternal weight gain and birth weight. RESULTS: Weight gain was 2.5 kg less in the women with gestational diabetes as compared with the controls (P = .0006). When adjusted for pregravid weight, maternal age, and gestational age at delivery, only underweight women with gestational diabetes persisted in having significantly less weight gain as compared with the control subjects (P = .035). There were no significant differences in infant birth weight between any gestational diabetes and control weight categories. The rate of weight gain was decreased in over-weight women with gestational diabetes versus control subjects in late pregnancy (P = .05). There was a significant correlation between maternal weight gain and birth weight in underweight (r = 0.46, P = .0001) and average-weight (r = 0.17, P = .02) control women but not in overweight controls or in any patients with gestational diabetes. CONCLUSION: Weight gain in women with gestational diabetes is less than in control patients, primarily because of greater pregravid weight, and does not correlate with neonatal birth weight.

Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes.

The purpose of this study was to characterize carbohydrate metabolism associated with the development of gestational diabetes. Six control (Ctl) and ten women with gestational diabetes mellitus (GDM) were evaluated using an intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp with [6,6-2H2]glucose prior to conception (P) and at 12-14 (E), and 34-36 wk of gestation (L). There was an increase (P = 0.0001) in first-phase insulin response in Ctl (P 174 +/- 133, E 388 +/- 120, and L 587 +/- 303 microU/ml) and GDM (P 197 +/- 94, E 267 +/- 77, and L 376 +/- 162 microU/ml) but a significant (P = 0.02) lag in change in GDM with advancing gestation. Basal endogenous glucose production increased during gestation [Ctl: P 2.74 +/- 0.23, E 2.62 +/- 0.38, and L 3.14 +/- 0.36; GDM: P 2.68 +/- 0.51, E 2.78 +/- 0.45, and L 2.98 +/- 0.48 mg.kg fat-free mass (FFM)-1 x min-1; P = 0.02], but there was resistance to suppression by insulin infusion (P = 0.03) in late gestation (GDM: 0.61 +/- 0.44 vs. Ctl: 0.16 +/- 0.17 mg.kg FFM-1 x min-1). Insulin sensitivity decreased during gestation (Ctl: P 10.78 +/- 2.78, E 8.34 +/- 2.36, and L 4.75 +/- 1.22; GDM: P 7.49 +/- 2.13, E 7.40 +/- 1.45, and L 4.21 +/- 1.01 mg.kg FFM-1 x min-1; P = 0.0001) and was primarily decreased (P = 0.04) in GDM compared with Ctl from P through E. These findings closely resemble those of non-insulin-dependent, predominantly insulin-resistant diabetes, which is often a sequel of GDM.

Longitudinal changes in basal hepatic glucose production and suppression during insulin infusion in normal pregnant women.

OBJECTIVE: The purpose of this study was to evaluate basal endogenous glucose production and suppression during insulin infusion in normal pregnant women. STUDY DESIGN: This prospective, longitudinal study was conducted at the Medical Center Hospital of Vermont. Six healthy women were evaluated before conception and at 12 to 14 and 34 to 36 weeks' gestation. Body composition was estimated by hydrodensitometry. Basal endogenous glucose production was estimated with a primed constant infusion of 6-6 2H2 glucose, and suppression of endogenous glucose production was estimated with insulin infusion during a hyperinsulinemic-euglycemic clamp. RESULTS: There was a significant (p = 0.02) 65% increase in fasting insulin concentration by late gestation. Moreover, there was a significant 30% (p = 0.0005) increase in basal endogenous glucose production (mg/min) with advancing gestation, which remained significant (p = 0.05) when corrected for fat-free mass. During insulin infusion endogenous glucose production was almost completely suppressed (i.e., > 90%) throughout gestation. CONCLUSIONS: There is a significant increase in basal endogenous glucose production at 34 to 36 weeks' gestation in spite of a significant increase in fasting insulin concentration. However, endogenous glucose production remains sensitive to insulin infusion throughout gestation.

Evaluation of fetal growth by estimation of neonatal body composition.

To characterize the variation in normal fetal growth by body composition analysis, 188 neonates from uncomplicated singleton term pregnancies were evaluated within 24 hours of birth. Anthropometric measures used to estimate lean body mass and body fat included the following: birth weight 3553 +/- 462 g, lean body mass 3060 +/- 377 g (86.3%), fat mass 495 +/- 196 g (13.7%), and ponderal index 2.65 +/- 0.25. There was a significant linear correlation between birth weight and lean body mass (r2 = 0.83, P = .0001), fat mass (r2 = 0.46, P = .0001), and ponderal index (r2 = 0.22, P = .001). Although the ponderal index has been used as an index of corpulence, the correlation between ponderal index and percent body fat was poor (r2 = 0.15). These results suggest that although neonatal fat mass constitutes only 14% of total birth weight, it explains 46% of its variance. In contrast, the ponderal index explains only 22% of the variance in birth weight and correlates poorly with percent body fat. Body composition analysis explains a significant amount of the variance in normal birth weight.

Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women.

To assess the longitudinal changes in insulin release and insulin sensitivity in nonobese normal women during gestation, six women were evaluated with oral glucose tolerance testing, body composition analysis, intravenous glucose tolerance tests, and the hyperinsulinemic-euglycemic clamp before conception, at 12 to 14 weeks, and at 34 to 36 weeks' gestation. There was a significant increase in the insulin/glucose ratio (p = 0.028) during the oral glucose tolerance test during gestation. There was also a significant 3.0- to 3.5-fold increase throughout gestation in first-phase (p = 0.001) and second-phase (p = 0.0001) insulin release during the intravenous glucose tolerance test. Peripheral insulin sensitivity was estimated as the glucose infusion rate (in milligrams per kilogram fat-free mass per minute) during the hyperinsulinemic-euglycemic clamp. There was a significant (p = 0.0003) 56% decrease in insulin sensitivity through 36 weeks' gestation. These results are the first to prospectively evaluate the longitudinal changes in maternal carbohydrate metabolism from the time before conception through late gestation with newer methods such as the hyperinsulinemic-euglycemic clamp.

Incidence and significance of islet cell antibodies in women with previous gestational diabetes.

Islet cell antibodies (ICAs) are markers for patients at risk for insulin-dependent diabetes and are associated with progressive beta-cell destruction. This prospective study was performed to estimate the incidence of these antibodies in 187 women with previous gestational diabetes. With a specific protein A monoclonal antibody (MoAb) assay, the incidence of ICAs was only 1.6% (3 of 187). Oral and intravenous glucose tolerance tests were performed in these 3 women and compared with 6 women with previous gestational diabetes without ICAs and 5 control women. Glucose tolerance was impaired only in the 3 women with ICAs, who also had an increase (P less than 0.03) in fasting plasma glucose and a decrease (P less than 0.03) in early first-phase insulin response. We conclude that the more specific MoAb method indicates a lower incidence of ICA in women with a history of gestational diabetes than previously reported and that a decreased first-phase insulin response is associated with the presence of ICAs, suggesting progressive islet cell damage.

Subclinical abnormalities of glucose metabolism in subjects with previous gestational diabetes.

To investigate whether there are subclinical abnormalities of glucose metabolism in women with previous gestational diabetes that are consistent with a high incidence of diabetes mellitus in later life, eight patients with previous gestational diabetes and normal oral glucose tolerance were evaluated by means of body composition studies, intravenous glucose tolerance tests, and the hyperinsulinemic-euglycemic clamp coupled with 6-6 dideuterated glucose infusion, indirect calorimetry, and measurement of islet cell antibodies. Eight control subjects were matched for percent body fat and diet and studied in a similar fashion. Abnormalities of insulin response and insulin resistance were present in four (50%) of patients with previous gestational diabetes. Insulin resistance was significantly greater in the patients than in the control subjects. When compared with lean patients, obese patients with previous gestational diabetes had significantly greater insulin response to the intravenous glucose tolerance test and insulin resistance. These changes are consistent with reported findings of an early and progressive development of overt diabetes in patients who had gestational diabetes.