Fibroblast Growth Factors 19 and 21 in Gestational Diabetes Mellitus
Condition: Gestational Diabetes Mellitus
MeSH terms: Diabetes, Gestational; Diabetes Mellitus
Study type: Interventional

Summary: 
      Gestational diabetes mellitus (GDM) is the most common complication in pregnancy. Both mother
      and offspring have a significantly increased future risk for metabolic and cardiovascular
      disease as a consequence of GDM. Pathological insulin resistance and the pancreatic β-cell
      dysfunction may contribute to the development and adverse outcomes of GDM.

      Recently, fibroblast growth factor 19 (FGF19) and FGF21 have emerged as key endocrine
      regulators of glucose, lipid and energy metabolism. Both factors activate FGFRs in the
      context of co-receptor βKlotho(KLB) expression. After that, both proteins alter ERK
      phosphorylation and stimulate glucose uptake. Furthermore, these two factors ameliorate
      insulin resistance through various ways including up-regulating insulin mRNA, IRS-1, GLUT-1
      expressions, down-regulating GH-IGF-1 levels in different tissues and blood circulation and
      also improving dyslipidemia.

      Our previous studies showed that several factors which involved in insulin resistance and
      FGF19/FGF21 signaling pathway had differential expression in placenta from GDM and normal
      glucose tolerance pregnancy. Those led us to hypothesize that FGF19/FGF21 signaling pathway
      could play an important role in the pathogenesis and development of insulin resistance state
      in GDM.

      In the present study, we will further investigate whether maternal and neonatal FGF19/FGF21
      signaling pathway are altered and associated with insulin resistance, glucose intolerance,
      dyslipidemia and adverse pregnancy outcomes. Thus we will evaluate the regulating action of
      FGF19/FGF21 on gestational insulin resistance.

      The aim of this study is to elucidate the role of FGF19/FGF21 in insulin resistance and
      metabolic disorder in GDM.
    

Detailed description: 
      First，30 pregnant women with GDM and 60 pregnant control women with normal glucose tolerance
      (NGT) matched for maternal and gestational age were enrolled in the study. All the subjects
      underwent antepartum screening in the First Affiliated Hospital of Sun Yat-sen University.
      Blood samples were obtained after overnight fasting at the time of oral glucose tolerance
      test (OGTT). Serum FGF19 and FGF21 levels were determined by enzyme-linked immunosorbent
      assay (ELISA) and were correlated with anthropometric, metabolic, and endocrine parameters.
      Homeostasis model assessment (HOMA-IR) index was calculated and analysed.

      Second, samples for measurement were obtained from 30 women with GDM and 35 healthy pregnant
      controls undergoing caesarean sections at term. mRNA and protein expression levels of
      FGF19/FGF21 and their co-receptor βKlotho（KLB）in placenta, rectus muscle and subcutaneous fat
      tissues were investigated with real-time quantitative polymerase chain reaction (qRT-PCR),
      western-blot and immunohistochemistry (IHC), respectively. Clinical data were collected and
      analysed.

      Data were analyzed by SPSS 20.0 database. The results were expressed as mean ± standard
      deviations or median with interquartile range. Differences between groups were assessed by
      Student's unpaired t test, Mann-Whitney U test, or Chi-square test as appropriate.
      Correlation analysis was performed using the Spearman rank correlation method. To identify
      independent relationships and adjust the effects of covariates, multiple linear regression
      analyses were performed. P values of <0.05 were considered significant.
    

Intervention name(s): biachemical detection
Intervention type(s): Diagnostic Test
Intervention description(s): Serum FGF19 and FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA) and were correlated with anthropometric, metabolic, and endocrine parameters. Homeostasis model assessment (HOMA-IR) index was calculated and analysed.
Second, samples for measurement were obtained from 30 women with GDM and 35 healthy pregnant controls undergoing caesarean sections at term. mRNA and protein expression levels of FGF19/FGF21 and their co-receptor βKlotho（KLB）in placenta, rectus muscle and subcutaneous fat tissues were investigated with real-time quantitative polymerase chain reaction (qRT-PCR), western-blot and immunohistochemistry (IHC), respectively. Clinical data were collected and analysed.
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Diagnostic
Keywords: GDM, FGF