Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1997 Oct 1;100(7):1775–1781. doi: 10.1172/JCI119704

Glucose turnover and gluconeogenesis in human pregnancy.

S Kalhan 1, K Rossi 1, L Gruca 1, E Burkett 1, A O'Brien 1
PMCID: PMC508362  PMID: 9312177

Abstract

The rate of appearance (Ra) of glucose in plasma and the contribution of gluconeogenesis were quantified in normal pregnant women early ( approximately 10 wk) and late ( approximately 34 wk) in gestation. Their data were compared with those of normal nonpregnant women. Glucose Ra was measured using the [U-13C]glucose tracer dilution method. Gluconeogenesis was quantified by the appearance of 2H on carbon 5 and 6 of glucose after deuterium labeling of body water pool. Weight-specific glucose Ra was unchanged during pregnancy (nonpregnant, 1.89+/-0.24; first trimester, 2.05+/-0.21; and third trimester 2.17+/-0.28 mg/kg.min, mean+/-SD), while total glucose Ra was significantly increased (early, 133.5+/-7.2; late, 162.6+/-16.4 mg/min; P = 0.005). The fractional contribution of gluconeogenesis via pyruvate measured by 2H enrichment on C-6 of glucose (45-61%), and of total gluconeogenesis quantified from 2H 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+/-15.9 mg/min; late pregnancy, 122.7+/-9.3 mg/min; P = 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.

Full Text

The Full Text of this article is available as a PDF (218.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Assel B., Rossi K., Kalhan S. Glucose metabolism during fasting through human pregnancy: comparison of tracer method with respiratory calorimetry. Am J Physiol. 1993 Sep;265(3 Pt 1):E351–E356. doi: 10.1152/ajpendo.1993.265.3.E351. [DOI] [PubMed] [Google Scholar]
  2. Casado J., Remesar X., Pastor-Anglada M. Hepatic uptake of amino acids in late-pregnant rats. Effect of food deprivation. Biochem J. 1987 Nov 15;248(1):117–122. doi: 10.1042/bj2480117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Catalano P. M., Tyzbir E. D., Wolfe R. R., Calles J., Roman N. M., Amini S. B., Sims E. A. Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes. Am J Physiol. 1993 Jan;264(1 Pt 1):E60–E67. doi: 10.1152/ajpendo.1993.264.1.E60. [DOI] [PubMed] [Google Scholar]
  4. Catalano P. M., Tyzbir E. D., Wolfe R. R., Roman N. M., Amini S. B., Sims E. A. Longitudinal changes in basal hepatic glucose production and suppression during insulin infusion in normal pregnant women. Am J Obstet Gynecol. 1992 Oct;167(4 Pt 1):913–919. doi: 10.1016/s0002-9378(12)80011-1. [DOI] [PubMed] [Google Scholar]
  5. Consoli A., Kennedy F., Miles J., Gerich J. Determination of Krebs cycle metabolic carbon exchange in vivo and its use to estimate the individual contributions of gluconeogenesis and glycogenolysis to overall glucose output in man. J Clin Invest. 1987 Nov;80(5):1303–1310. doi: 10.1172/JCI113206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Consoli A., Nurjhan N., Capani F., Gerich J. Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM. Diabetes. 1989 May;38(5):550–557. doi: 10.2337/diab.38.5.550. [DOI] [PubMed] [Google Scholar]
  7. Consoli A., Nurjhan N., Reilly J. J., Jr, Bier D. M., Gerich J. E. Mechanism of increased gluconeogenesis in noninsulin-dependent diabetes mellitus. Role of alterations in systemic, hepatic, and muscle lactate and alanine metabolism. J Clin Invest. 1990 Dec;86(6):2038–2045. doi: 10.1172/JCI114940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cowett R. M., Susa J. B., Kahn C. B., Giletti B., Oh W., Schwartz R. Glucose kinetics in nondiabetic and diabetic women during the third trimester of pregnancy. Am J Obstet Gynecol. 1983 Aug 1;146(7):773–780. doi: 10.1016/0002-9378(83)91076-1. [DOI] [PubMed] [Google Scholar]
  9. Felig P. Maternal and fetal fuel homeostasis in human pregnancy. Am J Clin Nutr. 1973 Sep;26(9):998–1005. doi: 10.1093/ajcn/26.9.998. [DOI] [PubMed] [Google Scholar]
  10. Ferrannini E., Barrett E. J., Bevilacqua S., DeFronzo R. A. Effect of fatty acids on glucose production and utilization in man. J Clin Invest. 1983 Nov;72(5):1737–1747. doi: 10.1172/JCI111133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Freinkel N. Banting Lecture 1980. Of pregnancy and progeny. Diabetes. 1980 Dec;29(12):1023–1035. doi: 10.2337/diab.29.12.1023. [DOI] [PubMed] [Google Scholar]
  12. Gilbert M., Sparks J. W., Girard J., Battaglia F. C. Glucose turnover rate during pregnancy in the conscious guinea pig. Pediatr Res. 1982 Apr;16(4 Pt 1):310–313. doi: 10.1203/00006450-198204000-00014. [DOI] [PubMed] [Google Scholar]
  13. Golden S., Chenoweth M., Dunn A., Okajima F., Katz J. Metabolism of tritium- and 14C-labeled alanine in rats. Am J Physiol. 1981 Aug;241(2):E121–E128. doi: 10.1152/ajpendo.1981.241.2.E121. [DOI] [PubMed] [Google Scholar]
  14. Hay W. W., Jr, Sparks J. W., Battaglia F. C., Meschia G. Maternal-fetal glucose exchange: necessity of a three-pool model. Am J Physiol. 1984 Jun;246(6 Pt 1):E528–E534. doi: 10.1152/ajpendo.1984.246.6.E528. [DOI] [PubMed] [Google Scholar]
  15. Hetenyi G., Jr, Lussier B., Ferrarotto C., Radziuk J. Calculation of the rate of gluconeogenesis from the incorporation of 14C atoms from labelled bicarbonate or acetate. Can J Physiol Pharmacol. 1982 Dec;60(12):1603–1609. doi: 10.1139/y82-237. [DOI] [PubMed] [Google Scholar]
  16. Jahoor F., Klein S., Wolfe R. Mechanism of regulation of glucose production by lipolysis in humans. Am J Physiol. 1992 Mar;262(3 Pt 1):E353–E358. doi: 10.1152/ajpendo.1992.262.3.E353. [DOI] [PubMed] [Google Scholar]
  17. Kalhan S. C., Adam P. A. Quantitative estimation of systemic glucose production in normal and diabetic pregnancy. Diabetes Care. 1980 May-Jun;3(3):410–415. doi: 10.2337/diacare.3.3.410. [DOI] [PubMed] [Google Scholar]
  18. Kalhan S. C., D'Angelo L. J., Savin S. M., Adam P. A. Glucose production in pregnant women at term gestation. Sources of glucose for human fetus. J Clin Invest. 1979 Mar;63(3):388–394. doi: 10.1172/JCI109314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kalhan S. C., Gilfillan C. A., Tserng K. Y., Savin S. M. Glucose-alanine relationship in normal human pregnancy. Metabolism. 1988 Feb;37(2):152–158. doi: 10.1016/s0026-0495(98)90010-5. [DOI] [PubMed] [Google Scholar]
  20. Kalhan S. C., Hertz R. H., Rossi K. Q., Savin S. M. Glucose-alanine relationship in diabetes in human pregnancy. Metabolism. 1991 Jun;40(6):629–633. doi: 10.1016/0026-0495(91)90055-2. [DOI] [PubMed] [Google Scholar]
  21. Kalhan S. C., Tserng K. Y., Gilfillan C., Dierker L. J. Metabolism of urea and glucose in normal and diabetic pregnancy. Metabolism. 1982 Aug;31(8):824–833. doi: 10.1016/0026-0495(82)90082-8. [DOI] [PubMed] [Google Scholar]
  22. Katz J. Determination of gluconeogenesis in vivo with 14C-labeled substrates. Am J Physiol. 1985 Apr;248(4 Pt 2):R391–R399. doi: 10.1152/ajpregu.1985.248.4.R391. [DOI] [PubMed] [Google Scholar]
  23. Krebs H. A., Hems R., Weidemann M. J., Speake R. N. The fate of isotopic carbon in kidney cortex synthesizing glucose from lactate. Biochem J. 1966 Oct;101(1):242–249. doi: 10.1042/bj1010242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Landau B. R. Estimating gluconeogenic rates in NIDDM. Adv Exp Med Biol. 1993;334:209–220. doi: 10.1007/978-1-4615-2910-1_15. [DOI] [PubMed] [Google Scholar]
  25. Landau B. R., Wahren J., Chandramouli V., Schumann W. C., Ekberg K., Kalhan S. C. Contributions of gluconeogenesis to glucose production in the fasted state. J Clin Invest. 1996 Jul 15;98(2):378–385. doi: 10.1172/JCI118803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Landau B. R., Wahren J., Chandramouli V., Schumann W. C., Ekberg K., Kalhan S. C. Use of 2H2O for estimating rates of gluconeogenesis. Application to the fasted state. J Clin Invest. 1995 Jan;95(1):172–178. doi: 10.1172/JCI117635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Magnusson I., Rothman D. L., Katz L. D., Shulman R. G., Shulman G. I. Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. J Clin Invest. 1992 Oct;90(4):1323–1327. doi: 10.1172/JCI115997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Marconi A. M., Davoli E., Cetin I., Lanfranchi A., Zerbe G., Fanelli R., Fennessey P. V., Pardi G., Battaglia F. C. Impact of conceptus mass on glucose disposal rate in pregnant women. Am J Physiol. 1993 Apr;264(4 Pt 1):E514–E518. doi: 10.1152/ajpendo.1993.264.4.E514. [DOI] [PubMed] [Google Scholar]
  29. Morriss F. H., Jr, Makowski E. L., Meschia G., Battaglia F. C. The glucose/oxygen quotient of the term human fetus. Biol Neonate. 1974;25(1-2):44–52. doi: 10.1159/000240677. [DOI] [PubMed] [Google Scholar]
  30. Nolan C. J., Proietto J. The feto-placental glucose steal phenomenon is a major cause of maternal metabolic adaptation during late pregnancy in the rat. Diabetologia. 1994 Oct;37(10):976–984. doi: 10.1007/BF00400460. [DOI] [PubMed] [Google Scholar]
  31. Nolan C. J., Proietto J. The set point for maternal glucose homeostasis is lowered during late pregnancy in the rat: the role of the islet beta-cell and liver. Diabetologia. 1996 Jul;39(7):785–792. doi: 10.1007/s001250050511. [DOI] [PubMed] [Google Scholar]
  32. Ogata E. S., Metzger B. E., Freinkel N. Carbohydrate metabolism in pregnancy XVI: longitudinal estimates of the effects of pregnancy on D-(63H) glucose and D-(6-14C) glucose turnovers during fasting in the rat. Metabolism. 1981 May;30(5):487–492. doi: 10.1016/0026-0495(81)90185-2. [DOI] [PubMed] [Google Scholar]
  33. Pastor-Anglada M., Champigny O., Ferré P., Remesar X., Girard J. Alanine turnover rate and its hepatic metabolism are increased in midpregnant rat. Biol Neonate. 1988;54(3):126–132. doi: 10.1159/000242843. [DOI] [PubMed] [Google Scholar]
  34. Pastor-Anglada M., Remesar X., Bourdel G. Alanine uptake by liver at midpregnancy in rats. Am J Physiol. 1987 Mar;252(3 Pt 1):E408–E413. doi: 10.1152/ajpendo.1987.252.3.E408. [DOI] [PubMed] [Google Scholar]
  35. Petersen K. F., Price T., Cline G. W., Rothman D. L., Shulman G. I. Contribution of net hepatic glycogenolysis to glucose production during the early postprandial period. Am J Physiol. 1996 Jan;270(1 Pt 1):E186–E191. doi: 10.1152/ajpendo.1996.270.1.E186. [DOI] [PubMed] [Google Scholar]
  36. Pimenta W., Nurjhan N., Jansson P. A., Stumvoll M., Gerich J., Korytkowski M. Glycogen: its mode of formation and contribution to hepatic glucose output in postabsorptive humans. Diabetologia. 1994 Jul;37(7):697–702. doi: 10.1007/BF00417694. [DOI] [PubMed] [Google Scholar]
  37. Puhakainen I., Yki-Järvinen H. Inhibition of lipolysis decreases lipid oxidation and gluconeogenesis from lactate but not fasting hyperglycemia or total hepatic glucose production in NIDDM. Diabetes. 1993 Dec;42(12):1694–1699. doi: 10.2337/diab.42.12.1694. [DOI] [PubMed] [Google Scholar]
  38. Rothman D. L., Magnusson I., Katz L. D., Shulman R. G., Shulman G. I. Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR. Science. 1991 Oct 25;254(5031):573–576. doi: 10.1126/science.1948033. [DOI] [PubMed] [Google Scholar]
  39. Tayek J. A., Katz J. Glucose production, recycling, and gluconeogenesis in normals and diabetics: a mass isotopomer [U-13C]glucose study. Am J Physiol. 1996 Apr;270(4 Pt 1):E709–E717. doi: 10.1152/ajpendo.1996.270.4.E709. [DOI] [PubMed] [Google Scholar]
  40. Tserng K. Y., Kalhan S. C. Estimation of glucose carbon recycling and glucose turnover with [U-13C] glucose. Am J Physiol. 1983 Nov;245(5 Pt 1):E476–E482. doi: 10.1152/ajpendo.1983.245.5.E476. [DOI] [PubMed] [Google Scholar]
  41. Valcarce C., Cuezva J. M., Medina J. M. Increased gluconeogenesis in the rat at term gestation. Life Sci. 1985 Aug 12;37(6):553–560. doi: 10.1016/0024-3205(85)90468-0. [DOI] [PubMed] [Google Scholar]
  42. Yang R. D., Matthews D. E., Bier D. M., Lo C., Young V. R. Alanine kinetics in humans: influence of different isotopic tracers. Am J Physiol. 1984 Nov;247(5 Pt 1):E634–E638. doi: 10.1152/ajpendo.1984.247.5.E634. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES