First-trimester follistatin-like-3 levels in pregnancies complicated by subsequent gestational diabetes mellitus

Abstract

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 (> or =2 abnormal values on a 100-g glucose tolerance test at approximately 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 approximately 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.

Figure 1

First-trimester FSTL3 levels in women who did and did not develop GDM. FSTL3 levels were measured in serum collected from women with GDM and control subjects at the first prenatal obstetric visit. FSTL3 levels were significantly lower in women who developed GDM (P < 0.001). Box plots depict the median (horizontal line in each box), the 25th percentile (bottom of each box), and the 75th percentile (top of each box). Box whiskers extend to the highest/lowest nonoutlier value. Outliers were defined as lying greater than three interquartile ranges outside the 25th or 75th percentile. Scatter plot overlay depicts levels of FSTL3 in individual subjects.

Figure 2

Odds of developing GDM by first-trimester FSTL3 tertile. Subjects were divided into tertiles based on the first-trimester FSTL3 level. Univariate (dark blue) and multivariate (light blue) logistic regression analyses were used to determine odds ratios for the development of GDM in each tertile. The multivariate logistic regression model includes adjustment for age, gestational age, diastolic blood pressure, BMI, nonwhite race, and multiparity. *Significantly different from the reference tertile at the P < 0.05 level.

Figure 3

Relationship between first trimester FSTL3 and GCT result. Glucose challenge test (GDM screening) was performed at 24–28 weeks of gestation. A 50-g glucose load was administered orally, and blood glucose was measured after 1 h. r = −0.30, P < 0.001 (Spearman correlation). Red markers represent GDM case subjects; blue markers represent control subjects.