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Vitamin D metabolites and binding protein predict preeclampsia in women with Type 1 diabetes: a cohort study
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  • Clare Kelly,
  • Carol Wagner,
  • Judy Shary,
  • Misti Leyva,
  • Jeremy Yu,
  • Alicia Jenkins,
  • Alison Nankervis,
  • Kristian Hanssen,
  • Satish Garg,
  • James Scardo,
  • Samar Hammad,
  • Christopher Aston,
  • Timothy Lyons
Clare Kelly
Medical University of South Carolina
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Carol Wagner
Medical University of South Carolina
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Judy Shary
Medical University of South Carolina
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Misti Leyva
Medical University of South Carolina
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Jeremy Yu
Medical University of South Carolina
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Alicia Jenkins
University of Sydney
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Alison Nankervis
Royal Women's Hospital
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Kristian Hanssen
Oslo University Hospital
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Satish Garg
University of Colorado
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James Scardo
Spartanburg Regional Medical Center
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Samar Hammad
Medical University of South Carolina
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Christopher Aston
The University of Oklahoma Health Sciences Center
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Timothy Lyons
Medical University of South Carolina
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Abstract

Objective: Preeclampsia (PE) occurs about four times more frequently in women with than without diabetes. Vitamin D is essential for healthy pregnancy. We investigated detailed measures of maternal plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and vitamin D binding protein (VDBP) to define associations with PE in women with Type 1 diabetes (T1DM). Design and setting: A multicentre prospective study in women at ~12, ~22 and ~32 weeks’ gestation (‘Visits’ (V) 1, 2, and 3, respectively). Population: We studied 23 T1DM women who subsequently developed PE, 24 who remained normotensive, and 19 non-diabetic, normotensive women (reference controls). Diabetic women were complication-free at V1, and all study visits preceded PE onset. Main Outcome Measures: Total, bioavailable, and free concentrations of 25(OH)D and 1,25(OH)2D; and VDBP. Results: 25(OH)D deficiency was more frequent in diabetic than non-diabetic women (69% vs 22%, p<0.05), but no measure of 25(OH)D predicted PE. In contrast, higher 1,25(OH)2D concentrations at V2 (total and bioavailable: p<0.01; free: p<0.05) and V3 (bioavailable: p<0.05; free: p<0.01) were associated with subsequent PE in T1DM women, as were lower concentrations of VDBP at V3 (p<0.05) and elevated ratios of 1,25(OH)2D/VDBP (V2, V3: p<0.01) and 1,25(OH)2D/25(OH)D (V3, p<0.05). Significance persisted after adjustment for covariates. Conclusions:In women with T1DM, concentrations of active vitamin D were higher, and VDBP lower, in the second and third trimesters in those who developed PE than in those who did not. Active vitamin D may serve as a new marker for PE risk, and could be implicated in pathogenesis.