Evidence in support of an association between betatrophin and insulin resistance (IR) is mounting, with studies demonstrating that betatrophin is elevated in patients with type 2 diabetes, obesity and gestational diabetes. The aim of this study was to evaluate the role of betatrophin in IR and physiological proliferation of beta cells during pregnancy in healthy women.

Eighty healthy pregnant women were examined at each trimester [T1 (first), T2 (second), T3 (third)], with a subgroup (n=45) that was also examined at 3 months postpartum (3MPP). The controls comprised 30 non-pregnant healthy women (HW) of reproductive age. Also measured were levels of betatrophin (ELISA), glucose (enzymatic method with hexokinase), insulin (IRMA), C-peptide (EASIA) and HbA_1c (HPLC), while HOMA-IR and HOMA-β scores were calculated.

Betatrophin concentration was highest at T1, and differed significantly from T2 and T3 (1.84 [Q₁=1.16, Q₃=2.67]ng/mL vs 1.46 [Q₁=0.96, Q₃=2.21]ng/mL; P<0.05 and 1.23 [Q₁=0.85, Q₃=2.14]ng/mL; P<0.01, respectively). The T3 median concentration of betatrophin was the lowest of all trimesters, and significantly lower than at 3MPP (1.23 [Q₁=0.85, Q₃=2.14]ng/mL vs 1.49 [Q₁=1.06, Q₃=2.60]ng/mL; P<0.01, respectively). At 3MPP, the level of betatrophin was similar to that of HW (1.47 [Q₁=0.89, Q₃=2.67]ng/mL). HOMA-IR and HOMA-%β index scores increased during gestation, peaking at T3 (2.3 [Q₁=1.66, Q₃=2.72] and 227.7 [Q₁=185.49, Q₃=326.31], respectively) and returning to levels similar to those of HW at 3MPP (1.53 [Q₁=1.12, Q₃=2.41] and 88.86 [Q₁=62.73, Q₃=130.45] vs 1.35 [Q₁=1.02, Q₃=1.62] and 92.5 [Q₁=74.20, Q₃=111.47], respectively).

Concentrations of betatrophin decrease during pregnancy, suggesting that the hormone does not play a significant role in the expansion of beta-cell mass and IR during pregnancy.