Plasma Vitamin D Metabolites and Binding Protein Predict Preeclampsia in Diabetic Women

by | Sep 1, 2020 | 2020, Diabetes, Pregnancy and Lactation, Vitamin D - General, Women's Health

Written by Angeline De Leon, Staff Writer. Study finds that in the late second trimester of pregnancy, 1,25-dihydroxyvitamin D (1,25(OH)2D) and the 1,25(OH)2D/ VDBP (vitamin D binding protein) ratio were good predictors of preeclampsia (PE), in women with type 1 diabetes.

women's health - pregnancyVitamin D serves several biological functions in the human body, its involvement ranging from immune function and bone development to insulin regulation and vascular health 1. During pregnancy, vitamin D levels are known to significantly fluctuate, with plasma concentrations of 1,25(OH)2D (active form of vitamin D) showing marked and continuous increases starting in the first trimester 2,3. In cases of vitamin D deficiency (defined as < 20 ng/mL) during pregnancy, poor health outcomes have been observed for both mother and child 4. Vitamin D deficiency has been linked to abnormal formation of placenta, altered development of blood vessels, as well as poorer cardiometabolic function 3,5. Insufficient levels of vitamin D are also associated with preeclampsia (PE), a complication involving high blood pressure and potential organ damage in mothers 6. Women with type 1 diabetes are not only more likely to be vitamin D deficient 7, they also have a 20% higher risk of developing PE 8. Animal research suggests that intake of 1,25(OH)2D can significantly mitigate symptoms of PE 9, however, studies in human models of PE are scarce. To this end, a recent study 10 published in Nutrients (2020) evaluated the relationship between plasma concentrations of 1,25(OH)2D and development of PE in diabetic women.

A longitudinal, prospective study was conducted with 23 women with type 1 diabetes and PE (mean age = 28.5 years), 24 women with type 1 diabetes without PE (mean age = 29.9 years), and 19 non-diabetic women as controls (mean age = 31.4 years). Enrollment began in the first trimester, and subjects were followed up until the time of delivery. Plasma and urine samples were collected during the first trimester, mid-second trimester, and early third trimester, and circulating levels of total, free, and bioavailable 1,25(OH)2D, 25(OH)D (measure of vitamin D status in the body), and VDBP were assessed.

Results showed that diabetic women were more likely to be deficient in 25(OH)D than non-diabetic women (69% vs. 22%, p = 0.009), however, 25(OH)D deficiency was not found to be associated with subsequent development of PE in diabetic women. By comparison, 1,25(OH)2D concentrations showed significant association with subsequent PE: higher concentrations of 1,25(OH)2D during the second trimester (p < 0.01 for total, bioavailable, and free) and third trimester (p < 0.05 for bioavailable, p < 0.01 for free) were associated with PE in diabetic women. Lower concentrations of VDBP in the third trimester were also associated with subsequent PE: each 1 mg/dL increase in VDBP during the third trimester was associated with an 8% reduction in risk of PE development (Odds Ratio = 0.92, p < 0.05).

Findings from the study suggest a unique profile of vitamin D metabolite and binding protein concentrations among diabetic women with PE. More specifically, concentrations of 1,25(OH)2D were higher during the second and third trimester of pregnancy, and concentrations of VDBP were lower during the third trimester. Additional analyses also showed that the ratio of total 1,25(OH)2D to VDBP during the second and third trimester were linked to subsequent PE, while 25(OH)D, the recognized metric for vitamin D, was not found to predict PE at all. Measures of 1,25(OH)2D and VDBP concentrations during the course of mid- to late-pregnancy, therefore, may serve as key biomarkers of PE. More studies are needed to determine whether a causal relationship exists between vitamin D status and PE and whether supplementation with vitamin D could modulate PE risk in diabetic women. Study limitations include a relatively small sample size, failure to account for potential differences in vitamin D metabolism, and the absence of subjects with sufficient levels of vitamin D.

Source: Kelly CB, Wagner CL, Shary JR, et al. Vitamin D metabolites and binding protein predict preeclampsia in women with type 1 diabetes. Nutrients. 2020; 12: 2048. DOI: 10.3390/nu12072048.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Posted September 1, 2020.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

References:

  1. Roth DE, Abrams SA, Aloia J, et al. Global prevalence and disease burden of vitamin D deficiency: a roadmap for action in low- and middle-income countries. Ann N Y Acad Sci. 2018;1430(1):44-79.
  2. Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2011;26(10):2341-2357.
  3. Ganguly A, Tamblyn JA, Finn-Sell S, et al. Vitamin D, the placenta and early pregnancy: effects on trophoblast function. The Journal of endocrinology. 2018;236(2):R93-r103.
  4. Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin D deficiency increases the risk of preeclampsia. The Journal of clinical endocrinology and metabolism. 2007;92(9):3517-3522.
  5. O’Callaghan KM, Kiely M. Systematic Review of Vitamin D and Hypertensive Disorders of Pregnancy. Nutrients. 2018;10(3).
  6. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):1122-1131.
  7. Azar M, Basu A, Jenkins AJ, et al. Serum carotenoids and fat-soluble vitamins in women with type 1 diabetes and preeclampsia: a longitudinal study. Diabetes Care. 2011;34(6):1258-1264.
  8. Persson M, Norman M, Hanson U. Obstetric and perinatal outcomes in type 1 diabetic pregnancies: A large, population-based study. Diabetes Care. 2009;32(11):2005-2009.
  9. Tian X, Ma S, Wang Y, et al. Effects of Placental Ischemia Are Attenuated by 1,25-Dihydroxyvitamin D Treatment and Associated with Reduced Apoptosis and Increased Autophagy. DNA and cell biology. 2016;35(2):59-70.
  10. Kelly CB, Wagner CL, Shary JR, et al. Vitamin D Metabolites and Binding Protein Predict Preeclampsia in Women with Type 1 Diabetes. Nutrients. 2020;12(7).