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

  • Efrath Barta and Arieh Drugan EMAIL logo
Published/Copyright: November 19, 2015
Journal of Perinatal Medicine
From the journal Journal of Perinatal Medicine Volume 44 Issue 4

Abstract

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

Methods: 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.

Results: 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.

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

Keywords: Blood glucose; diabetes; gestational diabetes; growth; pregnancy
Corresponding author: Arieh Drugan, MD, Rambam Health Care Campus and the Rappaport Faculty of Medicine, Department of Obstetrics and Gynecology, Technion Institute of Technology, POB 9602, Haifa 3109601, Israel, Tel.: +972 48542744, Fax: +972 48541778, E-mail:

Appendix A. Typical parameter values for the diabetic placenta

Here we elaborate on the calibration of the parameter values used by the theoretical simulation [9].

A1. Morphometric data

Most measurements [20–25] indicate that the shape of the terminal villi is preserved under diabetic conditions therefore, we entail here, as in Barta et al. [9], two confocal truncated spheroids to describe the two bordering membranes. We assume that a diabetic terminal villus has the same length as a normal one but a slightly larger radius, rt and that the diabetic BM expands as a result of the increased capillaries surface area. Table A1 specifies the details of our choice of parameter values that induces: 4% and 15.5% higher villi surface area and 8% and 30% higher villi volume for GDM and PGDM, respectively. The BM encloses a volume which is 18% and 42% higher than in control while its surface area is 8.5% and 20% higher for GDM and PGDM, respectively. The distance for the diffusion of glucose (i.e. the average thickness of the syncytiotrophoblast) does not change.

Table A1

Parameter values used in the theoretical simulation for various diabetic conditions.

ParameterNormalGDMPGDM
Radius of a terminal villus, rt22 μm23 μm25 μm
Radius of the BM, rc16.5 μm18 μm20 μm
Consumption rate constant, kg0.0025 s–10.0018 s–10.0017 s–1
Permeability constant at MVM, P0g0.3×10–6 cms–10.23×10–6 cms–10.23×10–6 cms–1
Permeability constant at BM, P1g1.2×10–6 cms–10.92×10–6 cms–10.92×10–6 cms–1
Translocation rate constant, koMVM4×10–5 cms–13.5×10–5 cms–13.2×10–5 cms–1
Translocation rate constant, koBM4×10–5 cms–13.5×10–5 cms–13.2×10–5 cms–1
Glut1 concentration at MVM, CGLUTMVM16 mM16 mM16 mM
Glut1 concentration at BM, CGLUTBM5 mM5.3 mM7 mM

A2. Glucose utilization rate

Osmond et al. [14, 23] detected a major decrease of glucose utilization in the placenta under GDM. When simulating GDM, we reduced the control value of the glucose utilization rate constant kg by more than 25%. Based on Osmond et al. [14] and Haugel et al. [26] we assumed a slightly higher than normal glucose utilization in PGDM. This implies almost similar kg values for GDM and PGDM in spite of the high glucose level in PGDM.

A3. Permeability of membranes

Honda et al. [20] measured diabetic BM to be 67% thicker than the normal BM and others [27, 28] reported on thickening of the BM that varies from minimal to very prominent. Diabetic MVM has a reduced fluidity and increased cholesterol content [23]. These findings, related to higher micro-viscosity of the syncytiotrophoblast membranes in GDM [29], led us to reduce the permeability constants for simple diffusion at the two bordering membranes (P0g , P1g) to about 77% of their normal values.

A4. GLUT1 characteristics

We concluded in the past [9] that the most probable scenario is one with a symmetric activity of glucose transporters at the two faces of the two membranes. There are no experimental evidences regarding the effect of diabetic conditions on the translocation rate constants koMVM and koBM therefore, we assumed that they are decreased as the permeability constants do.

The glucose diffusion rate within the syncytiotrophoblast and affinities of the transporter and glucose at the two faces of both membranes remain unchanged under diabetic conditions [10, 16, 19, 30].

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The authors stated that there are no conflicts of interest regarding the publication of this article.

Received: 2015-3-12
Accepted: 2015-10-23
Published Online: 2015-11-19
Published in Print: 2016-5-1

©2016 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Obesity and gestational diabetes in pregnancy: an evolving epidemic
  4. Original articles - Diabetes
  5. Is omitting the 3rd hour measurement in the 100 g oral glucose tolerance test feasible?
  6. Maternal hypoglycemia on 50 g glucose challenge test: outcomes are influenced by fetal gender
  7. Biological and biochemical characteristics of a Mediterranean population with Gestational Diabetes Mellitus
  8. Maternal and perinatal outcomes after bariatric surgery: a case control study
  9. A population-based comparison between actual maternal weight gain and the Institute of Medicine weight gain recommendations in singleton pregnancies
  10. The relationship between cesarean section rate in term singleton pregnancies, maternal weight, and weight gain during pregnancy
  11. Antenatal body mass index (BMI) and weight gain in pregnancy – its association with pregnancy and birthing complications
  12. A clinical study which relates to a theoretical simulation of the glucose transport in the human placenta under various diabetic conditions
  13. Academy’s Corner
  14. American medical education: the evolution of excellence
  15. Original articles - Obstetrics
  16. Is epidural analgesia during labor related to retained placenta?
  17. Preventing intellectual disability during pregnancy: what are the potentially high yield targets?
  18. Evaluation of measured postpartum blood loss after vaginal delivery using a collector bag in relation to postpartum hemorrhage management strategies: a prospective observational study
  19. Original articles - Fetus
  20. Mutation analysis and prenatal diagnosis in a Chinese family with succinic semialdehyde dehydrogenase and a systematic review of the literature of reported ALDH5A1 mutations
  21. Original articles - Newborn
  22. Neurological disease or intellectual disability among sons of female Swedish dental personnel
  23. Seeking the best training model for difficult conversations in neonatology
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  26. Congress Calendar
  27. Congress Calendar
https://doi.org/10.1515/jpm-2015-0091
Keywords for this article
Blood glucose; diabetes; gestational diabetes; growth; pregnancy

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Obesity and gestational diabetes in pregnancy: an evolving epidemic
  4. Original articles - Diabetes
  5. Is omitting the 3rd hour measurement in the 100 g oral glucose tolerance test feasible?
  6. Maternal hypoglycemia on 50 g glucose challenge test: outcomes are influenced by fetal gender
  7. Biological and biochemical characteristics of a Mediterranean population with Gestational Diabetes Mellitus
  8. Maternal and perinatal outcomes after bariatric surgery: a case control study
  9. A population-based comparison between actual maternal weight gain and the Institute of Medicine weight gain recommendations in singleton pregnancies
  10. The relationship between cesarean section rate in term singleton pregnancies, maternal weight, and weight gain during pregnancy
  11. Antenatal body mass index (BMI) and weight gain in pregnancy – its association with pregnancy and birthing complications
  12. A clinical study which relates to a theoretical simulation of the glucose transport in the human placenta under various diabetic conditions
  13. Academy’s Corner
  14. American medical education: the evolution of excellence
  15. Original articles - Obstetrics
  16. Is epidural analgesia during labor related to retained placenta?
  17. Preventing intellectual disability during pregnancy: what are the potentially high yield targets?
  18. Evaluation of measured postpartum blood loss after vaginal delivery using a collector bag in relation to postpartum hemorrhage management strategies: a prospective observational study
  19. Original articles - Fetus
  20. Mutation analysis and prenatal diagnosis in a Chinese family with succinic semialdehyde dehydrogenase and a systematic review of the literature of reported ALDH5A1 mutations
  21. Original articles - Newborn
  22. Neurological disease or intellectual disability among sons of female Swedish dental personnel
  23. Seeking the best training model for difficult conversations in neonatology
  24. Meconium aspiration syndrome in infants of HIV-positive women: a case-control study
  25. Dopamine treatment does not need speed recovery of newborns from transient tachypnea
  26. Congress Calendar
  27. Congress Calendar
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