Vitamin D supplementation and the effects on glucose metabolism during pregnancy: a randomized controlled trial.
OBJECTIVE
Vitamin D deficiency in pregnancy is associated with an increased risk of gestational diabetes mellitus (GDM) and neonatal vitamin D deficiency. We conducted a double-blind, randomized controlled trial of low-dose (LD) versus high-dose (HD) vitamin D supplementation to investigate the effects of vitamin D supplementation on glucose metabolism during pregnancy.


METHODS
Women with plasma 25-hydroxyvitamin D (25OHD) levels <32 ng/mL before 20 weeks' gestation were randomized to oral vitamin D3 at 5,000 IU daily (HD) (n = 89) or the recommended pregnancy dose of 400 IU daily (LD) (n = 90) until delivery. The primary end point was maternal glucose levels on oral glucose tolerance test (OGTT) at 26-28 weeks' gestation. Secondary end points included neonatal 25OHD, obstetric and other neonatal outcomes, and maternal homeostasis model assessment of insulin resistance. Analysis was by intention to treat.


RESULTS
There was no difference in maternal glucose levels on OGTT. Twelve LD women (13%) developed GDM versus seven (8%) HD women (P = 0.25). Neonatal cord 25OHD was higher in HD offspring (46 ± 11 vs. 29 ± 12 ng/mL, P < 0.001), and deficiency was more common in LD offspring (24 vs. 10%, P = 0.06). Post hoc analysis in LD women showed an inverse relationship between pretreatment 25OHD and both fasting and 2-h blood glucose level on OGTT (both P < 0.001). Baseline 25OHD remained an independent predictor after multiple regression analysis.


CONCLUSIONS
HD vitamin D supplementation commencing at a mean of 14 weeks' gestation does not improve glucose levels in pregnancy. However, in women with baseline levels <32 ng/mL, 5,000 IU per day was well tolerated and highly effective at preventing neonatal vitamin D deficiency.
Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, AustraliaFaculty of Medicine, Western Clinical School, University of Sydney, Sydney, New South Wales, Australia constanceyap@yahoo.com.
Constance
C
Yap
Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, AustraliaFaculty of Medicine, Western Clinical School, University of Sydney, Sydney, New South Wales, Australia.
N Wah
NW
Cheung
Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, AustraliaFaculty of Medicine, Western Clinical School, University of Sydney, Sydney, New South Wales, AustraliaDiabetes and Transcription Factors Group, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Jenny E
JE
Gunton
Obstetrics and Gynaecology, Westmead Hospital, Sydney, New South Wales, Australia.
Neil
N
Athayde
Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
Craig F
CF
Munns
Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, Australia.
Anna
A
Duke
Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, AustraliaSchool of Medicine, University of Western Sydney, Sydney, New South Wales, Australia.
Mark
M
McLean
D000328:Adult; D002762:Cholecalciferol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016640:Diabetes, Gestational / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000150:complications / Q000188:drug therapy*; D055815:Young Adult
D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D; D005947:Glucose