A computational model of 1,5‐AG dynamics during pregnancy
Abstract
The importance of 1,5-anhydroglucitol (1,5-AG) as an intermediate biomarker for diabetic pregnancy is multi-fold: (1) it serves as a reliable indicator of moderate-level glycemic control, especially during early gestation; (2) it has been associated with increased risk of diabetes, independent of HbA1c and fasting glucose; and (3) it is an independent risk factor for the development of eclampsia during pregnancy. However, the clinical use of this biomarker during pregnancy has been underutilized due to physiological changes in glomerular filtration rate, plasma volume, and other hemodynamic parameters which have been hypothesized to bias gestational serum 1,5-AG concentrations. Here, we develop an in-silico model of gestational 1,5-AG by combining pre-existing physiological data in the literature with a two-compartment mathematical model, building off of a previous kinetic model described by Stickle and Turk (1997) Am. J. Physiol., 273, E821. Our model quantitatively characterizes how renal and hemodynamic factors impact measured 1,5-AG during normal pregnancy and during pregnancy with gestational diabetes and diabetes mellitus. During both normal and diabetic pregnancy, we find that a simple two-compartment model of 1,5-AG kinetics, with all parameters but reabsorption fraction adjusted for time in pregnancy, efficiently models 1,5-AG kinetics throughout the first two trimesters. Allowing reabsorption fraction to decrease after 25 weeks permits parameters closer to expected physiological values during the last trimester. Our quantitative model of 1,5-AG confirms the involvement of hypothesized renal and hemodynamic mechanisms during pregnancy, clarifying the expected trends in 1,5-AG to aid clinical interpretation. Further research and data may elucidate biological changes during the third trimester that account for the drop in 1,5-AG concentrations, and clarify physiological differences between diabetes subtypes during pregnancy.
Additional Information
© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Version of Record online: 21 Aug 2017. Manuscript Accepted: 3 Jul 2017. Manuscript Revised: 1 Jul 2017. Manuscript Received: 26 May 2017. The authors would like to extend their gratitude to Meryem Ok for her insightful comments and support on this endeavor. This work was funded by the Massachusetts Institute of Technology IDEAS Global Challenge and Caltech George W. Housner Student Discovery Fund.Attached Files
Published - Zekavat_et_al-2017-Physiological_Reports.pdf
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Additional details
- PMCID
- PMC5582262
- Eprint ID
- 80650
- Resolver ID
- CaltechAUTHORS:20170821-141748525
- Massachusetts Institute of Technology (MIT)
- Caltech George W. Housner Student Discovery Fund
- Created
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2017-08-21Created from EPrint's datestamp field
- Updated
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2022-03-23Created from EPrint's last_modified field