J Perinat Med. 2016 May 1;44(4):405-10. doi: 10.1515/jpm-2015-0091. 

A clinical study which relates to a theoretical simulation of the glucose transport in the human placenta under various diabetic conditions.

Barta E, Drugan A.

Barcod Computers Ltd and Department of Obstetrics and Gynecology, Rambam Health Care Campus, the Technion Faculty of Medicine, Haifa, Israel




To characterize placental glucose delivery under normoglycemic conditions, gestational and pre-gestational diabetes and to relate the clinical data to theoretical predictions.


Data from 125 pregnancies: 50 normal gestations and 75 ones with various types of diabetes were collected. In parallel, we formulated a theoretical model for the transport of glucose under various diabetic conditions. Measured glucose blood levels were fed into the theoretical model that predicts glucose supply to the fetus and the results were confronted with measured fetal weights.


Measured fetal weight and computed glucose delivery in gestational diabetic parturients resemble the situation in normal pregnancies. However, pre-gestational diabetes has a major effect as it involves heavier fetuses and enhanced computed glucose fluxes via placental membranes.


Fetal weight (increased in pre-gestational and unaltered in gestational diabetes) correlates with the predicted rate of glucose delivery through the placenta. 

PMID: 26584352          DOI:10.1515/jpm-2015-0091 



Diabetes mellitus (DM) is a common complication of pregnancy that may be first manifested during pregnancy (gestational diabetes mellitus = GDM) or may have pre-gestational origins (PGDM). It may affect both mother and fetus. About 7% of pregnancies are com­plicated by DM; 90% of those rep­resent women with GDM [1]. Especially during the first trimester, the diabetic milieu influences placental development and function – thickening of the trophoblastic basement membrane and some edematous changes of the villous stroma that are compensated by an increased surface of exchange in the periphery of the villous tree and by capillary hyper-vascularization [2]. In term placentas from insulin-dependent DM pregnancies, the expression of the glucose transporter GLUT1 and mediated glucose uptake in the basal membrane of the syncytiotrophoblast are probably upregulated by hyperglycaemia acting in early pregnancy. Thus, placental functional changes related to diabetes are expected to be more pronounced in PGDM than in GDM; the latter is expressed clinically late in the second trimester and has not been shown to be associated with changes in placental glucose transporting capacity in vitro [3]. However, despite intensive glycemic control, fetal macrosomia (defined as birth weight higher than 4000 gr) complicates as many as 40% of diabetic pregnancies.


In this study we evaluated maternal and neonatal glucose levels in normoglicemic and in diabetic pregnancies and the rate of macrosomia in the different groups. The maternal and fetal glucose levels were fed into a theoretical model which is based on our earlier simulation [4,5] of glucose transport in the placentas of healthy women. We found that the effect of maternal diabetes on placental glucose transport to the fetus is expressed mainly in PGDM patients while in GDM the changes are minimal. In GDM, glucose fluxes are close to normal, while in PGDM glucose delivery is more than twice the normal value. PGDM involves a lower translocation rate via the membranes and a higher transporter density there. We found that the mean fetal weight in the GDM group did not differ significantly from the control, however fetal weight in the PGDM group was about 20% higher than in controls. In all diabetics, glucose blood levels of both mothers and fetuses were significantly different from the control values. Neonatal arterial and venous glucose levels under GDM conditions conform with those previously reported [3]. In PGDM both the glucose gradient between the mother and the fetus (shown to highly affect the glucose delivery [5]) and the difference between gf and gfa (0.94mM in PGDM versus 0.41mM in control group) are significantly increased. These might explain the varying percentage of macrosomic fetuses, defined as birth weight ≥ 4000g in our study: 44% in the PGDM group, as compared to 11.5% in GDM pregnancies and 7.7% in controls ( χ2= 8.54, p=0.003).


Based on the model of glucose transport we demonstrated here a correlation between measured fetal weight and computed glucose delivery rate. Our study suggests that it is not the higher glucose concentration but rather the higher glucose flux through the placenta that results in fetal macrosomia. As suggested by Desoye et al. [6], fetal macrosomia is the result of placental failure to manage excess glucose and to store it in the form of glycogen. The reflux of glucose from the fetus into the placenta is increased in diabetes as a result of fetal hyperglycemia and of excess of the storage capacity of fetal glycogen. These processes, mediated by the glucose transporters GLUT1 and GLUT3 on cells surrounding the fetoplacental vasculature, might be under the control of fetal insulin, since insulin injected into the fetal circulation increases placental glycogen stores.


In previous work we showed that the glucose flux is to a leading order a function of the product of the GLUT1 concentration and of the translocation rate constants [4] but this product hardly changes under diabetic conditions. In addition, although the PGDM placenta devours more glucose, the glucose delivery to the fetus was shown here to be just slightly sensitive with respect to this factor. We speculate that as long as the diabetic mother is under control (and her glucose level is lower than 12mM ) the antagonist effects of the thicker, more viscous diabetic membranes and the higher expression of the transporter leaves the gradient of the glucose concentration as the “single player” that determines the fluxes; they are raised but don’t cause fatal harms. When hyperglycemia prevails, the transporter density declines in order to lessen the extremely high, harmful glucose flux. An alteration of the transporter’s affinity, its translocation rate, density of the transporter, placental metabolic rate or a combination of all those might contribute to the enhanced glucose flux under PGDM condition. However, the characteristics of the diabetic basement membrane, namely its GLUT1 concentrations and the translocation rate constants, seem to play the most important role.



  1. Albrecht SS, Kuklina EV, Bansil P, Jamieson DJ, Whiteman MK, Kourtis AP, et al. Diabetes trends among delivery hospitalizations in the US 1994-2004. Diabetes Care 2010; 33:768-73.
  2. Vambergue A, Fajardy I. Consequences of gestational and pregestational diabetes on placental function and birth weight    World J Diabetes 2011; 2(11):196-203.
  3. Taricco E, Radaelli T, Rossi G, Nobile de Santis M, Bulfamante G, Avagliano L, Cetin I. Effects of gestational diabetes on fetal oxygen and glucose levels in vivo. BJOG 2009;
  4. Barta E, Drugan A. Glucose transport from mother to fetus-a theoretical study. J. Theor. Biol. 2010; 263(3):295-302.
  5. Barta E, Drugan A. A theoretical model of glucose transports suggests symmetric GLUT1 characteristics at placental membranes.  J. Memb. Biol. 2014; 247:685-94
  6. Desoye G, Korgun ET, Ghaffari-Tabrizi N, Hahn T. Is fetal macrosomia in adequately controlled diabetic women the result of a placental defect? – a hypothesis.  Journal of Maternal–Fetal and Neonatal Medicine 2002; 11:258-61.



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