Relationship between Maternal and Fetal Plasma Glucose and Insulin Concentrations during Graded Maternal Hyperglycemic States in Primates

 

 Buy Article Permissions and Reprints

ABSTRACT

Our goal was to conduct a controlled study using an established timed-pregnant baboon model to describe the maternal and fetal plasma glucose and insulin concentrations during graded increases in maternal circulating glucose levels. Timed-pregnant baboons were operated on during the second half of pregnancy, and after recovery from surgery, maternal glucose infusions were started. To determine changes in plasma glucose and insulin concentrations, maternal and fetal blood samples were obtained before glucose infusion and at 30-minute intervals to include 30 minutes postinfusion. Maternal plasma glucose concentrations ranged from 97 to 392 mg/dL and fetal plasma glucose concentrations from 78 to 278 mg/dL. Maternal plasma insulin concentrations ranged from 123 to 1384 U/mL, and the fetal plasma insulin concentrations from 76 to 260 U/mL. Significant correlations were noted between maternal plasma glucose and insulin concentrations (N = 10; R ², 80%; p < 0.001), as well as maternal and fetal plasma glucose concentrations (N = 10; R ², 97%; p < 0.001). Maternal-to-fetal glucose gradient ranged from 16 to 34% (mean, 23%) and did not correlate with maternal plasma glucose concentration. No correlation was found between fetal plasma glucose and insulin concentration. Maternal-to-fetal insulin gradient ranged from 31 to 87% (mean, 70.7%) and was significantly different from the glucose gradient (p < 0.0001). Results from this study suggests that (1) there is a relatively steady transplacental glucose transfer during the second half of pregnancy at maternal plasma glucose concentrations ranging from 97 to 392 mg/dL; and (2) there is also a relative incapacity of the fetal pancreas, compared with the maternal pancreas, to respond to graded increases of hyperglycemia. Studies aimed at determining whether particular thresholds of maternal hyperglycemia at different gestational ages can lead to transitory hyperosmolar and polyuric fetal states could provide further insights into the mechanisms leading to idiopathic polyhydramnios.

REFERENCES

• 1 Edlund H. Pancreatic organogenesis-developmental mechanisms and implications for therapy.  Nat Rev Genet. 2002;  3 524-532
  PubMedGoogle Scholar
• 2 Bell G I, Pictet R L, Rutter W J, Cordell B, Tischer E, Goodman H M. Sequence of the human insulin gene.  Nature. 1980;  284 26-32
  PubMedGoogle Scholar
• 3 Adesanya T, Grillo I, Shima K. Insulin content and enzyme histochemistry of the human foetal pancreatic islet.  J Endocrinol. 1966;  36 151-158
  PubMedGoogle Scholar
• 4 Espinosa de los Monteros A, Driscoll S G, Steinke J. Insulin release from isolated human fetal pancreatic islets.  Science. 1970;  168 1111-1112
  PubMedGoogle Scholar
• 5 Milner R D, Hill D J. Fetal growth control: the role of insulin and related peptides.  Clin Endocrinol (Oxf). 1984;  21 415-433
  PubMedGoogle Scholar
• 6 Sara V R, Hall K, Misaki M, Fryklund L, Christensen N, Wetterberg L. Ontogenesis of somatomedin and insulin receptors in the human fetus.  J Clin Invest. 1983;  71 1084-1094
  PubMedGoogle Scholar
• 7 Pedersen J, Bojsen-Moller B, Poulsen H. Blood sugar in newborn infants of diabetic mothers.  Acta Endocrinol (Copenh). 1954;  15 33-52
  PubMedGoogle Scholar
• 8 Bell A W, Kennaugh J M, Battaglia F C, Makowski E L, Meschia G. Metabolic and circulatory studies of fetal lamb at midgestation.  Am J Physiol. 1986;  250 E538-E544
  PubMedGoogle Scholar
• 9 Nicolini U, Hubinont C, Santolaya J, Fisk N M, Coe A M, Rodeck C H. Maternal-fetal glucose gradient in normal pregnancies and in pregnancies complicated by alloimmunization and fetal growth retardation.  Am J Obstet Gynecol. 1989;  161 924-927
  PubMedGoogle Scholar
• 10 Nicolini U, Hubinont C, Santolaya J, Fisk N M, Rodeck C H. Effects of fetal intravenous glucose challenge in normal and growth retarded fetuses.  Horm Metab Res. 1990;  22 426-430
  Article in Thieme ConnectPubMedGoogle Scholar
• 11 Herring J M, Fortman J D, Anderson R J, Bennett B T. Ultrasonic determination of fetal parameters in baboons (Papio anubis).  Lab Anim Sci. 1991;  41 602-605
  PubMedGoogle Scholar
• 12 Santolaya-Forgas J, Romero R, Mehendale R. The effect of continuous morphine administration on maternal plasma oxytocin concentration and uterine contractions after open fetal surgery.  J Matern Fetal Neonatal Med. 2006;  , In press
  PubMedGoogle Scholar
• 13 Susa J B, Neave C, Sehgal P, Singer D B, Zeller W P, Schwartz R. Chronic hyperinsulinemia in the fetal rhesus monkey. Effects of physiologic hyperinsulinemia on fetal growth and composition.  Diabetes. 1984;  33 656-660
  PubMedGoogle Scholar
• 14 De Prins F A, Hill D J, Fekete M et al.. Reduced plasma somatomedin activity and costal cartilage sulfate incorporation activity during experimental growth retardation in the fetal rat.  Pediatr Res. 1984;  18 1100-1104
  PubMedGoogle Scholar
• 15 Hill D J, Milner R D. Insulin as a growth factor.  Pediatr Res. 1985;  19 879-886
  CrossrefPubMedGoogle Scholar
• 16 Henry J B. Clinical Diagnosis and Management by Laboratory Methods. 17th ed. Philadelphia; WB Saunders 1984: 411
  Google Scholar

Joaquin Santolaya-ForgasM.D. Ph.D. 

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, WSU/Hutzel Women's Hospital

3990 John R Road, 7 Brush North, Detroit, MI, 48201