Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 Jul;74(1):279–286. doi: 10.1172/JCI111412

Effects of chronic fetal hyperglycemia upon oxygen consumption in the ovine uterus and conceptus.

A F Philipps, P J Porte, S Stabinsky, T S Rosenkrantz, J R Raye
PMCID: PMC425210  PMID: 6429196

Abstract

Hyperglycemia has been shown to induce arterial hypoxemia in the chronically catheterized fetal sheep. To investigate the mechanism behind this glucose-induced hypoxemia, eight pregnant ewes and their fetuses were studied. Fetal glucose infusion (11.9 +/- 0.6 mg glucose/kg per min) was associated with a doubling of the fetal plasma glucose concentration with concomitant elevation of the umbilical vein-distal arterial O2 content difference by 24 h of infusion (P less than 0.01). Calculated fetal O2 consumption increased from 8.1 +/- 0.4 ml/kg per min in the control period to a maximum value of 10.6 +/- 0.3 ml/kg per min by third infusion day (P less than 0.01), which is an increase of approximately 30%. The degree of stimulation of fetal O2 consumption was related to the degree of fetal hyperglycemia but not to the degree of fetal hyperinsulinemia. The increase in fetal O2 consumption was accompanied by a significant increase in fetal O2 extraction with no change in either fetal O2 delivery or fetal blood O2 affinity. In addition, fetal hypercapnea with a mild fetal respiratory acidosis was induced by fetal hyperglycemia. The increase in fetal arterial PCO2 was linearly related (P less than 0.001) to the magnitude of increase in fetal O2 consumption. These studies suggest that chronic fetal hyperglycemia induces a state of accelerated fetal oxidative metabolism and may be important in explaining the etiology behind certain unusual findings in human infants of diabetic mothers.

Full text

PDF
284

Selected References

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

  1. Abrams R., Caton D., Clapp J., Barron D. H. Thermal and metabolic features of life in utero. Clin Obstet Gynecol. 1970 Sep;13(3):549–564. doi: 10.1097/00003081-197009000-00005. [DOI] [PubMed] [Google Scholar]
  2. Askanazi J., Carpentier Y. A., Elwyn D. H., Nordenström J., Jeevanandam M., Rosenbaum S. H., Gump F. E., Kinney J. M. Influence of total parenteral nutrition on fuel utilization in injury and sepsis. Ann Surg. 1980 Jan;191(1):40–46. doi: 10.1097/00000658-198001000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Askanazi J., Elwyn D. H., Silverberg P. A., Rosenbaum S. H., Kinney J. M. Respiratory distress secondary to a high carbohydrate load: a case report. Surgery. 1980 May;87(5):596–598. [PubMed] [Google Scholar]
  4. Askanazi J., Rosenbaum S. H., Hyman A. I., Silverberg P. A., Milic-Emili J., Kinney J. M. Respiratory changes induced by the large glucose loads of total parenteral nutrition. JAMA. 1980 Apr 11;243(14):1444–1447. [PubMed] [Google Scholar]
  5. Battaglia F. C., Meschia G. Principal substrates of fetal metabolism. Physiol Rev. 1978 Apr;58(2):499–527. doi: 10.1152/physrev.1978.58.2.499. [DOI] [PubMed] [Google Scholar]
  6. Blechner J. N. Fetal acid-base homeostasis. Clin Obstet Gynecol. 1970 Sep;13(3):621–637. doi: 10.1097/00003081-197009000-00010. [DOI] [PubMed] [Google Scholar]
  7. Boyd R. D., Morriss F. H., Jr, Meschia G., Makowski E. L., Battaglia F. C. Growth of glucose and oxygen uptakes by fetuses of fed and starved ewes. Am J Physiol. 1973 Oct;225(4):897–902. doi: 10.1152/ajplegacy.1973.225.4.897. [DOI] [PubMed] [Google Scholar]
  8. Boyle P. C., Storlien L. H., Harper A. E., Keesey R. E. Oxygen consumption and locomotor activity during restricted feeding and realimentation. Am J Physiol. 1981 Nov;241(5):R392–R397. doi: 10.1152/ajpregu.1981.241.5.R392. [DOI] [PubMed] [Google Scholar]
  9. Carson B. S., Philipps A. F., Simmons M. A., Battaglia F. C., Meschia G. Effects of a sustained insulin infusion upon glucose uptake and oxygenation of the ovine fetus. Pediatr Res. 1980 Feb;14(2):147–152. doi: 10.1203/00006450-198002000-00016. [DOI] [PubMed] [Google Scholar]
  10. Cowett R. M., Schwartz R. The infant of the diabetic mother. Pediatr Clin North Am. 1982 Oct;29(5):1213–1231. doi: 10.1016/s0031-3955(16)34256-0. [DOI] [PubMed] [Google Scholar]
  11. Ditzel J., Standl E. The problem of tissue oxygenation in diabetes mellitus. Acta Med Scand Suppl. 1975;578:59–68. doi: 10.1111/j.0954-6820.1975.tb06503.x. [DOI] [PubMed] [Google Scholar]
  12. Fernandez Mondejar E., Duro Lombardo M., Perez de la Cruz A. J., Merida Morales A., Torres Ruiz J. M., Ferron Orihuela J. A. Variations in oxygen consumption and carbon dioxide production during parenteral nutrition. Intensive Care Med. 1982;8(4):169–172. doi: 10.1007/BF01725733. [DOI] [PubMed] [Google Scholar]
  13. Gelman S. R., Spellacy W. N., Wood S., Birk S. A., Buhi W. C. Fetal movements and ultrasound: effect of maternal intravenous glucose administration. Am J Obstet Gynecol. 1980 Jun 15;137(4):459–461. doi: 10.1016/0002-9378(80)91128-x. [DOI] [PubMed] [Google Scholar]
  14. Hill E. P., Power G. G., Longo L. D. A mathematical model of carbon dioxide transfer in the placenta and its interaction with oxygen. Am J Physiol. 1973 Feb;224(2):283–299. doi: 10.1152/ajplegacy.1973.224.2.283. [DOI] [PubMed] [Google Scholar]
  15. Itskovitz J., Goetzman B. W., Rudolph A. M. Effects of hemorrhage on umbilical venous return and oxygen delivery in fetal lambs. Am J Physiol. 1982 Apr;242(4):H543–H548. doi: 10.1152/ajpheart.1982.242.4.H543. [DOI] [PubMed] [Google Scholar]
  16. Itskovitz J., LaGamma E. F., Rudolph A. M. The effect of reducing umbilical blood flow on fetal oxygenation. Am J Obstet Gynecol. 1983 Apr 1;145(7):813–818. doi: 10.1016/0002-9378(83)90684-1. [DOI] [PubMed] [Google Scholar]
  17. James E. J., Raye J. R., Gresham E. L., Makowski E. L., Meschia G., Battaglia F. C. Fetal oxygen consumption, carbon dioxide production, and glucose uptake in a chronic sheep preparation. Pediatrics. 1972 Sep;50(3):361–371. [PubMed] [Google Scholar]
  18. Katz J., Rognstad R. Futile cycles in the metabolism of glucose. Curr Top Cell Regul. 1976;10:237–289. doi: 10.1016/b978-0-12-152810-2.50013-9. [DOI] [PubMed] [Google Scholar]
  19. Keitt A. S. Reduced nicotinamide adenine dinucleotide-linked analysis of 2,3-diphosphoglyceric acid: spectrophotometric and fluorometric procedures. J Lab Clin Med. 1971 Mar;77(3):470–475. [PubMed] [Google Scholar]
  20. Koong L. J., Garrett W. N., Rattray P. V. A description of the dynamics of fetal growth in sheep. J Anim Sci. 1975 Oct;41(4):1065–1068. doi: 10.2527/jas1975.4141065x. [DOI] [PubMed] [Google Scholar]
  21. Lorijn R. H., Longo L. D. Norepinephrine elevation in the fetal lamb: oxygen consumption and cardiac output. Am J Physiol. 1980 Jul;239(1):R115–R122. doi: 10.1152/ajpregu.1980.239.1.R115. [DOI] [PubMed] [Google Scholar]
  22. Lorijn R. H., Nelson J. C., Longo L. D. Induced fetal hyperthyroidism: cardiac output and oxygen consumption. Am J Physiol. 1980 Sep;239(3):H302–H307. doi: 10.1152/ajpheart.1980.239.3.H302. [DOI] [PubMed] [Google Scholar]
  23. MACKAY R. B. Observations of the oxygenation of the foetus in normal and abnormal pregnancy. J Obstet Gynaecol Br Emp. 1957 Apr;64(2):185–197. doi: 10.1111/j.1471-0528.1957.tb02619.x. [DOI] [PubMed] [Google Scholar]
  24. NAEYE R. L. INFANTS OF DIABETIC MOTHERS: A QUANTITATIVE, MORPHOLOGIC STUDY. Pediatrics. 1965 Jun;35:980–988. [PubMed] [Google Scholar]
  25. Natale R., Patrick J., Richardson B. Effects of human maternal venous plasma glucose concentrations on fetal breathing movements. Am J Obstet Gynecol. 1978 Sep 1;132(1):36–41. doi: 10.1016/0002-9378(78)90795-0. [DOI] [PubMed] [Google Scholar]
  26. PEDERSEN J., BOJSEN-MØLLER B., POULSEN H. Blood sugar in newborn infants of diabetic mothers. Acta Endocrinol (Copenh) 1954 Jan;15(1):33–52. doi: 10.1530/acta.0.0150033. [DOI] [PubMed] [Google Scholar]
  27. Peeters L. L., Sheldon R. E., Jones M. D., Jr, Makowski E. L., Meschia G. Blood flow to fetal organs as a function of arterial oxygen content. Am J Obstet Gynecol. 1979 Nov 1;135(5):637–646. doi: 10.1016/s0002-9378(16)32989-1. [DOI] [PubMed] [Google Scholar]
  28. Philipps A. F., Carson B. S., Meschia G., Battaglia F. C. Insulin secretion in fetal and newborn sheep. Am J Physiol. 1978 Nov;235(5):E467–E474. doi: 10.1152/ajpendo.1978.235.5.E467. [DOI] [PubMed] [Google Scholar]
  29. Philipps A. F., Widness J. A., Garcia J. F., Raye J. R., Schwartz R. Erythropoietin elevation in the chronically hyperglycemic fetal lamb. Proc Soc Exp Biol Med. 1982 May;170(1):42–47. doi: 10.3181/00379727-170-41394. [DOI] [PubMed] [Google Scholar]
  30. Philips A. F., Dubin J. W., Matty P. J., Raye J. R. Arterial hypoxemia and hyperinsulinemia in the chronically hyperglycemic fetal lamb. Pediatr Res. 1982 Aug;16(8):653–658. doi: 10.1203/00006450-198208000-00013. [DOI] [PubMed] [Google Scholar]
  31. Rudolph A. M., Heymann M. A. Cardiac output in the fetal lamb: the effects of spontaneous and induced changes of heart rate on right and left ventricular output. Am J Obstet Gynecol. 1976 Jan 15;124(2):183–192. doi: 10.1016/s0002-9378(16)33296-3. [DOI] [PubMed] [Google Scholar]
  32. Rurak D. W., Gruber N. C. The effect of neuromuscular blockade on oxygen consumption and blood gases in the fetal lamb. Am J Obstet Gynecol. 1983 Jan 15;145(2):258–262. doi: 10.1016/0002-9378(83)90502-1. [DOI] [PubMed] [Google Scholar]
  33. Saltzman H. A., Salzano J. V. Effects of carbohydrate metabolism upon respiratory gas exchange in normal men. J Appl Physiol. 1971 Feb;30(2):228–231. doi: 10.1152/jappl.1971.30.2.228. [DOI] [PubMed] [Google Scholar]
  34. Widness J. A., Susa J. B., Garcia J. F., Singer D. B., Sehgal P., Oh W., Schwartz R., Schwartz H. C. Increased erythropoiesis and elevated erythropoietin in infants born to diabetic mothers and in hyperinsulinemic rhesus fetuses. J Clin Invest. 1981 Mar;67(3):637–642. doi: 10.1172/JCI110078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wilkening R. B., Meschia G. Fetal oxygen uptake, oxygenation, and acid-base balance as a function of uterine blood flow. Am J Physiol. 1983 Jun;244(6):H749–H755. doi: 10.1152/ajpheart.1983.244.6.H749. [DOI] [PubMed] [Google Scholar]

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

RESOURCES