Glucose metabolism during fasting through human pregnancy: comparison of tracer method with respiratory calorimetry

Abstract

Glucose turnover and glucose oxidation were quantified in six normal pregnant women serially throughout pregnancy, using [U-13C]glucose tracer in combination with open-circuit indirect respiratory calorimetry. Five normal nonpregnant women were studied for comparison. With advancing gestation and increase in maternal body weight, there was a proportionate increase in the rate of appearance (Ra) of glucose so that Ra expressed per kilogram body weight did not change from the first to third trimester. The tracer measured rate of glucose oxidation expressed per kilogram body weight also did not change significantly throughout pregnancy. Oxygen consumption (VO2) in pregnant subjects did not differ from that in nonpregnant subjects. However, the respiratory exchange ratio (RER) increased significantly during pregnancy (0.88 +/- 0.53 3rd trimester and 0.76 +/- 0.50 nonpregnant, P < 0.01). The estimated contribution of carbohydrate to VO2 measured by respiratory calorimetry was greater than that measured by the tracer method. This discrepancy became wider as the respiratory quotient increased in late pregnancy. These data suggest that maternal glucose metabolism adjusts throughout pregnancy to meet the increased demands of the conceptus. The discrepancy between tracer method and respiratory calorimetry was probably due to the contribution of (fetal) lipogenesis and (maternal) gluconeogenesis to RER.

Glucose turnover and gluconeogenesis in human pregnancy.

“…The maternal and fetal glucose pools have been shown to be in equilibrium in human and in other species, and a rapid transfer of glucose along a concentration gradient has been demonstrated. Using tracer isotope dilution methods, it has been shown that with advancing gestation there is an increase in the rate of appearance of glucose in the maternal circulation (2,(4)(5)(6), and that this increase is related to the increase in weight of the mother, and to the mass of the conceptus (7). Freinkel described pregnancy as a state of accelerated starvation, wherein there is a rapid decline in maternal glucose concentration during periods of fasting as well as an increase in circulating ketones (8).…”

“…Such inference was based upon the observed unchanged rate of urea excretion in early pregnancy (9), and decreased rate of urea synthesis after an overnight fast in late pregnancy (4). Using [2,[3][4][5][6][7][8][9][10][11][12][13] C 2 ]alanine tracer, we have previously observed a decreased incorporation of alanine C in glucose in humans in late gestation (10). Since the tracer C of alanine or lactate may be lost, in part via exchanges at the oxaloacetate level, the use of C-labeled gluconeogenic precursors results in underestimation of the contribution of gluconeogenesis (11).…”

“…The dose of prime was adjusted depending upon the prevailing glucose concentration. The rate of tracer infusion was checked at the end of each study, as described (4,6).…”

“…The rate of glucose appearance was calculated from the dilution of uniformly labeled glucose in plasma, as described (6).…”

Maternal and Fetal Carbohydrate, Lipid and Protein Metabolisms

“…Glucose production from the glycogen depots in the liver also contributes hyperglycemia (11). In pregnancy basal hepatic glucose production has been shown to increase by 16-30% to meet the increasing needs of fetus (5,12). In spite of progressive decrease in insulin sensitivity with advancing pregnancy, endogenous hepatic glucose production was shown to remain sensitive to increased insulin concentration in normal pregnancy (1).…”