Glucose turnover and gluconeogenesis in human pregnancy.

Abstract

The rate of appearance (Ra) of glucose in plasma and the contribution of gluconeogenesis were quantified in normal pregnant women early ( ‫ف‬ 10 wk) and late ( ‫ف‬ 34 wk) in gestation. Their data were compared with those of normal nonpregnant women. Glucose Ra was measured using the [U Ϫ 13 C]glucose tracer dilution method. Gluconeogenesis was quantified by the appearance of 2 H on carbon 5 and 6 of glucose after deuterium labeling of body water pool. Weightspecific glucose Ra was unchanged during pregnancy (nonpregnant, 1.89 Ϯ 0.24; first trimester, 2.05 Ϯ 0.21; and third trimester 2.17 Ϯ 0.28 mg/kg·min, mean Ϯ SD), while total glucose Ra was significantly increased (early, 133.5 Ϯ 7.2; late, 162.6 Ϯ 16.4 mg/min; P ϭ 0.005). The fractional contribution of gluconeogenesis via pyruvate measured by 2 H enrichment on C-6 of glucose (45-61%), and of total gluconeogenesis quantified from 2 H enrichment on C-5 of glucose (i.e., including glycerol [68-85%]) was not significantly different between pregnant and nonpregnant women. Inasmuch as total glucose Ra was significantly increased, total gluconeogenesis was also increased in pregnancy (early pregnancy, 94.7 Ϯ 15.9 mg/min; late pregnancy, 122.7 Ϯ 9.3 mg/min; P ϭ 0.003). These data demonstrate the ability of the mother to adapt to the increasing fetal demands for glucose with advancing gestation. The mechanism for this unique quantitative adjustment to the fetal demands remains undefined. ( J. Clin. Invest. 1997. 100:1775-1781.)

Pathophysiology of postprandial hyperglycaemia in women with type 1 diabetes during pregnancy

“…In the fasted state, glucose production and disposal rates were well matched in early and late gestation, with no differences between our study population and what had previously been described in healthy pregnancy [1]. In addition, we found no changes in glucose bioavailability or postprandial glucose appearance between early and late gestation.…”

“…A similar study using [6,6-2 H 2 ]glucose and [U- 13 C] glucose tracers in healthy pregnant women (seven in early and five in late gestation) was performed by Kalhan et al [1]. After a prolonged fast (14 h), they also found increases in total gluconeogenesis but no changes in EGP or glucose disposal rates, when adjusted for maternal weight gain.…”

“…Data from healthy pregnant women suggest that the mother adapts to the increasing fetal demands for glucose by increasing both the total rate of appearance of glucose and the endogenous glucose production in late gestation [1]. Women with type 1 diabetes spend on average 8 h per day in hyperglycaemia in late gestation, with most hyperglycaemic excursions following meals [2].…”

“…Carbohydrate digestion rates and gastric emptying are complex, with both intra-and interindividual variability, and in people with type 1 diabetes are further influenced by pre-meal glucose control [19]. Pregnancy adds further challenges of tight postprandial glucose control targets (<7.8 mmol/l at 1 h) as well as dynamic alterations in EGP, insulin kinetics and gastric emptying [1,20,21].…”

Unlike pregnant adult women, pregnant adolescent girls cannot maintain glycine flux during late pregnancy because of decreased synthesis from serine

“…It has been proposed that this is due to an inability of the adolescent mother to provide the nutrient needs for her own growth and the growth of her fetus. In particular, the requirement for amino acids increases as pregnancy progresses in order to sustain increased rates of protein deposition (3) and to support increased availability of glucose through gluconeogenesis (4) .Dispensable amino acids comprise the bulk of maternal amino acids transferred to the fetus in pregnancy (5) . A good example is glycine, which is a provider of methyl groups needed for the synthesis of DNA necessary for cell division to support maternal and fetal tissue deposition (6,7) .…”