First-Trimester Follistatin-Like-3 Levels in Pregnancies Complicated by Subsequent Gestational Diabetes Mellitus

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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 (≥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.