Serum concentrations of fibroblast growth factors 19 and 21 in women with gestational diabetes mellitus: association with insulin resistance, adiponectin, and polycystic ovary syndrome history.

BACKGROUND: Fibroblast growth factor 19 (FGF19) and FGF21 are considered to be novel adipokines that improve glucose tolerance and insulin sensitivity. In the current study, we investigated serum FGF19 and FGF21 levels in patients with gestational diabetes mellitus (GDM) and explored their relationships with anthropometric and endocrine parameters. METHOD: Serum FGF19 and FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA) in patients with GDM (n = 30) and healthy pregnant controls (n = 60) matched for maternal and gestational age. Serum FGF19 and FGF21 levels were correlated with anthropometric, metabolic, and endocrine parameters. RESULTS: Circulating levels of FGF19 were significantly reduced in patients with GDM relative to healthy pregnant subjects, whereas FGF21 levels were increased in GDM patients. Serum FGF19 levels independently and inversely correlated with insulin resistance (increased homeostasis model assessment of insulin resistance, HOMA-IR) and were positively related to serum adiponectin in both groups. In contrast, serum FGF21 levels independently and positively correlated with insulin resistance and serum triglycerides and were inversely related to serum adiponectin. In addition, in the combined population of both groups, those women with preconception polycystic ovary syndrome (PCOS) history had the lowest levels of FGF19, which were significantly lower than those in GDM patients without PCOS history and those in controls without PCOS history. CONCLUSIONS: Circulating FGF19 levels are reduced in GDM patients, in contrast with FGF21 levels. Both serum FGF19 and FGF21 levels are strongly related to insulin resistance and serum levels of adiponectin. Considering the different situation between FGF19 and FGF21, we suggest that reduced serum FGF19 levels could be involved in the pathophysiology of GDM, while increased serum FGF21 levels could be in a compensatory response to this disease

Relationships of FGF19 and FGF21 with clinical, anthropometric and biochemical parameters calculated in a combined population of healthy pregnant controls and patients with GDM (n = 90).

<p>The correlations were calculated in the combined population of GDM patients and controls. Units and abbreviations are as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081190#pone-0081190-t001" target="_blank">Table 1</a>.</p><p>*Significant correlation as assessed by Spearman correlation method.</p

Multiple linear regression analysis between FGF19 (dependent variable) and age, BMI, HOMA-IR, adiponectin, and PCOS history, as well as between FGF21 (dependent variable) and age, BMI, HOMA-IR, adiponectin and TG.

<p>β Coefficients and P values are given. Abbreviations are indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081190#pone-0081190-t001" target="_blank">Table 1</a>.</p><p>*Significant correlation.</p

General characteristics of the study participants.

<p>Data are presented as means and SD, counts, or medians and interquartile ranges, as appropriate. HOMA-IR: homeostasis model of insulin resistance; HDL: high-density lipoprotein; LDL: low-density lipoprotein. <i>P</i> values are presented for comparison between GDM subjects and control subjects. The characteristics of the PCOS group are shown.</p

Scattergram of serum FGF19 levels in patients with PCOS history, GDM patients without PCOS history.

<p>Horizontal lines across the scatter diagram represent median values. Differences between groups were assessed by Mann-Whitney <i>U</i> test with Bonferroni adjustment for multiple testing.</p

Scattergram of serum FGF21 levels in patients with PCOS history, GDM patients without PCOS history.

<p>Horizontal lines across the scatter diagram represent median values. Differences between groups were assessed by Mann-Whitney <i>U</i> test with Bonferroni adjustment for multiple testing.</p

Fetal growth is associated with maternal fasting plasma glucose at first prenatal visit.

Fasting plasma glucose (FPG) concentration measured at the first prenatal visit is a predictor of gestational diabetes mellitus (GDM); however, whether this test is indicative of fetal growth has not been clarified. Thus, the purpose of this study was to determine whether birth weight and birth length were related to FPG levels at the first prenatal visit.Research samples were collected from pregnant women who took an FPG test at their first prenatal visit (10-24 gestational weeks), received regular prenatal care, and delivered in our center. FPG value, maternal pre-gravid BMI, weight gain before FPG test, before and after Oral Glucose Tolerance Test (OGTT), neonatal birthweight, birth length, Ponderal Index and birthing method were recorded for analysis. Data were analyzed by independent sample t test, Pearson correlation, and Chi-square test, followed by partial correlation or logistic regression to confirm differences. Statistical significance level was α = 0.05.2284 pregnant women, including 462 GDM and 1822 with normal glucose tolerance (NGT) were recruited for the present study. FPG concentration at the first prenatal visit was associated with neonatal birth weight (partial correlation coefficient r' = 0.089, P<0.001) and birth length (partial correlation coefficient r' = 0.061, P = 0.005), but not with Ponderal Index or birthing method. Maternal pre-gravid BMI was associated with FPG value (partial correlation coefficient r' = 0.113, P<0.001). FPG concentration at the first prenatal visit (OR = 2.945, P<0.001), weight gain before OGTT test (OR = 1.039, P = 0.010), and age (OR = 1.107, P<0.001) were independent related factors of GDM.Fasting plasma glucose concentration at the first prenatal visit is associated with fetal growth. Maternal pre-gravid BMI and weight gain are related to glucose metabolism

Baseline characteristics of the research population.

<p>Baseline characteristics of the research population.</p

Relationship between fasting plasma glucose concentration, pre-gravid BMI and weight gain before FPG test.

<p>Panel A. FPG is associated with pre-gravid BMI across the tested population. Panel B. FPG is associated with weight gain before FPG test in GDM group.</p

Relationship between maternal glycemic metabolism, maternal weight pattern and neonatal birthweight, birth length and Ponderal index.

<p>Partial correlation between FPG concentration and birth weight, birth length and Ponderal index were adjusted with maternal age, pre-gravid BMI, weight gain before and after OGTT, gestational age, GDM diagnosis and neonatal gender. r: correlation coefficient; r′: partial correlation coefficient.</p><p>Relationship between maternal glycemic metabolism, maternal weight pattern and neonatal birthweight, birth length and Ponderal index.</p