Person:

Powe, Camille

Objective: To determine whether maternal levels of follistatin-like-3 (FSTL3), an inhibitor of activin and myostatin involved in glucose homeostasis, are altered in the first trimester of pregnancies complicated by subsequent gestational diabetes mellitus (GDM). Research Design and Methods: This was a nested case-control study of subjects enrolled in a prospective cohort of pregnant women with and without GDM ((\geq)2 abnormal values on a 100-g glucose tolerance test at ~28 weeks of gestation). We measured FSTL3 levels in serum collected during the first trimester of pregnancy. Logistic regression analyses were used to determine the risk of GDM. Results: Women who developed GDM (n = 37) had lower first-trimester serum levels of FSTL3 compared with women who did not (n = 127) (median 10,789 [interquartile range 7,013-18,939] vs. 30,670 [18,370-55,484] pg/ml, P < 0.001). When subjects were divided into tertiles based on FSTL3 levels, women with the lowest levels demonstrated a marked increase in risk for developing GDM in univariate (odds ratio 11.2 [95% CI 3.6-35.3]) and multivariate (14.0 [4.1-47.9]) analyses. There was a significant negative correlation between first-trimester FSTL3 levels and ~28-week nonfasting glucose levels (r = -0.30, P < 0.001). Conclusions: First-trimester FSTL3 levels are associated with glucose intolerance and GDM later in pregnancy.

Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the bioavailable vitamin D (that fraction not bound to vitamin D binding protein) associates more strongly with measures of mineral metabolism than total levels, we identified 94 patients with previously measured 25(OH)D and 1,25-dihydroxyvitamin D ((1,25(OH)_2D)) from a cohort of incident hemodialysis patients. Vitamin D binding protein was measured from stored serum samples. Bioavailable 25(OH)D and (1,25(OH)_2D) were determined using previously validated formulae. Associations with demographic factors and measures of mineral metabolism were examined. When compared with whites, black patients had lower levels of total, but not bioavailable, 25(OH)D. Bioavailable, but not total, 25(OH)D and (1,25(OH)_2D) were each significantly correlated with serum calcium. In univariate and multivariate regression analysis, only bioavailable 25(OH)D was significantly associated with parathyroid hormone levels. Hence, bioavailable vitamin D levels are better correlated with measures of mineral metabolism than total levels in patients on hemodialysis.

Context: Changes in vitamin D binding protein (DBP) concentrations and catabolism of 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D (24,25D) after vitamin D2 supplementation may alter concentrations and bioavailability of circulating 25-hydroxyvitamin D (25D). Objective: Examine acute changes in vitamin D metabolism and bioavailability after vitamin D2 supplementation. Methods: Study design was secondary analysis of a single-arm interventional study. Thirty consenting volunteers were treated with five 50,000 IU oral doses of ergocalciferol over 2 weeks. Main outcome measures included concentrations of DBP, vitamin D metabolites, and bioavailable 25-hydroxyvitamin D (25D) in pre- and posttreatment serum samples. Results: After supplementation, 25D2 (mean ± standard deviation) increased from 1.4 ± 0.9 ng/mL to 45.3 ± 16.5 ng/mL (P < 0.0001), and 25D3 levels decreased from 26.8 ± 9.9 ng/mL to 19.7 ± 8.2 ng/mL (P < 0.0001). Total 25D (25D2 plus 25D3) increased from 28.2 ± 10.0 ng/mL to 65.0 ± 21.1 ng/mL (152.2% ± 102.5%; P < 0.0001). DBP and total 24,25D concentrations increased 39.1% ± 39.4% (165.6 ± 53.8 µg/mL to 222.0 ± 61.1 µg/mL; P < 0.0001) and 31.3% ± 48.9% (3.9 ± 2.0 ng/mL to 4.7 ± 2.1 ng/mL; P = 0.0147), respectively. In contrast to total 25D, bioavailable 25D increased by 104.4% ± 99.6% (from 5.0 ± 2.0 ng/mL to 8.7 ± 2.7 ng/mL; P < 0.001), and 1,25D increased by 32.3% ± 38.8% (from 45.5 ± 10.7 pg/mL to 58.1 ± 13.0 pg/mL; P = 0.0006). There were no changes in calcium or parathyroid hormone (P > 0.05 for both). Conclusion: Changes after vitamin D2 supplementation involve acute rise in serum DBP and 24,25D, both of which may attenuate the rise in bioavailable 25D and 1,25D.