Longitudinal changes in body composition and energy balance in lean women with normal and abnormal glucose tolerance during pregnancy.

OBJECTIVE: The objective of this study was to evaluate the longitudinal changes in energy expenditure and body composition in relationship to alterations in carbohydrate metabolism in women with normal and abnormal glucose metabolism. We hypothesized that women with decreased insulin sensitivity before conception would have less fat accretion and smaller increases in energy expenditure. STUDY DESIGN: Six women with normal glucose tolerance and 10 women with abnormal glucose tolerance were evaluated before conception, and in early (12 to 14 weeks) and late (34 to 36 weeks) gestation. Body composition was estimated by hydrodensitometry, resting energy expenditure, and glucose and fat metabolism by indirect calorimetry, endogenous glucose production by infusion of [6-6 2H2] glucose, and insulin sensitivity using a hyperinsulinemic-euglycemic clamp (40 mU/m2/min). RESULTS: There was a smaller increase in fat mass (1.3 kg [P = .04]) in early pregnancy in women with abnormal glucose tolerance before pregnancy. Indirect calorimetry measured gestational age-related increases in basal oxygen utilization, with or without correction for fat-free mass (VO2, P = .002), resting energy expenditure (expressed in kilocalories, P = .0001), and carbohydrate oxidation (P = .0003). The insulin-mediated elevation in VO2 increased in later gestation VO2 (P = .005), as did resting energy expenditure (P = .0001) and fat oxidation (P = 0.0001). However, there was a decrease in respiratory quotient (P = .0001), carbohydrate oxidation (P = .002), and nonoxidative carbohydrate metabolism (P = .0001) with advancing gestation during insulin infusion. In early pregnancy, changes in fat mass correlated inversely with changes in insulin sensitivity (r= -0.52, P = .04) and changes in basal VO2 correlated inversely with decreases in basal endogenous glucose production (r = -0.74, P = .01). CONCLUSION: In early gestation, the changes in maternal fat mass and basal oxygen consumption are inversely related to the changes in insulin sensitivity. This response in lean women with decreased insulin sensitivity before conception may have survival value by providing a larger amount of available substrate to meet fetoplacental needs during gestation.

The effect of oral terbutaline on maternal glucose metabolism and energy expenditure in pregnancy.

OBJECTIVE: Terbutaline, a selective beta2-agonist, is a frequently used tocolytic known to affect maternal metabolism. The purpose of this study was to evaluate the effect of oral terbutaline on maternal glucose metabolism and energy expenditure. STUDY DESIGN: Six healthy pregnant women with normal glucose tolerance were evaluated between 30 and 34 weeks' gestation. Oral terbutaline was administered to determine the effects on hepatic glucose production with [6-6(2)H2] glucose tracer, insulin sensitivity (hyperinsulinemic-euglycemic clamp), and energy expenditure (indirect calorimetry). Terbutaline, insulin, and glucagon levels were also obtained. Subjects were randomly assigned to either oral terbutaline 5 mg every 6 hours for 24 hours or no medication. Repeat studies were conducted 1 week apart, each subject serving as her own control. RESULTS: In the basal state terbutaline was associated with a trend toward increased basal glucose levels (81.6 +/- 6.6 vs 93.7 +/- 12.0 mg/dl, p = 0.06) but no significant increase in hepatic glucose production (3.2 +/- 0.3 vs 3.6 +/- 0.4 mg/kg fat-free mass/min, p = 0.23). However, there was a significant increase in basal insulin concentration (17.6 +/- 9.2 vs 25.6 +/- 10.4 microU/ml, p = 0.02). There was a 28% decrease in insulin sensitivity as measured by the glucose infusion rate during the euglycemic clamp plus residual hepatic glucose turnover (5.78 +/- 1.91 vs 4.16 +/- 1.49 mg/kg fat-free mass/min, p = 0.005). Glucagon concentration was significantly decreased both in the basal state (163 +/- 26 vs 144 +/- 27 pg/ml, p = 0.0007) and during the clamp (144 +/- 27 vs 133 +/- 27 pg/ml, p = 0.003). Basal oxygen consumption increased 9% (270 +/- 49 vs 294 +/- 50 ml oxygen/min, p = 0.007) and caloric expenditure 14% (1.32 +/- 0.23 vs 1.50 +/- 0.31 kcal/min, p = 0.025) or 260 kcal/day with terbutaline. CONCLUSION: Decreased peripheral insulin sensitivity, and to a lesser degree increased endogenous glucose production, may represent the pathophysiology of abnormal glucose tolerance observed in many women treated with oral terbutaline. Common side effects such as tremors and tachycardia experienced by many women on a regimen of terbutaline are consistent with our finding of a significant increase in basal energy expenditure.