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NCT Number: NCT01858597

Fibroblast Growth Factors 19 and 21 in Gestational Diabetes Mellitus

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.

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Key information

Age range

18 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Obstetrics and Gynechology Department of the 1st affiliated hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Women with singleton pregnancy;
  • Regular antenatal examination from the first trimester;
  • Give birth in the university hospital (The 1st affiliated hospital of Sun Yat-sen University)

Exclusion criteria

  • Younger than 18 years old;
  • Older than 40 years old;
  • Multiple pregnancy;
  • Diagnosed DM before pregnancy;
  • Complicated with other diseases such as hypertension, eclampsia, thyroid diseases, etc.;
  • Taking any drug that affect glucose and lipid metabolism and insulin sensitivity.

Treatment and study plan

biachemical detection

Diagnostic Test

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.

Primary outcomes

  1. The Concentration of Serum FGF19

    Time frame: in fasting state during 24-28 gestational weeks

Secondary outcomes

  1. Expression of FGF19 in Term Placenta

    Time frame: term delivery (when participants come back to hospital to give birth during 37-41 gestational weeks)

Sponsors and collaborators

Lead sponsor

First Affiliated Hospital, Sun Yat-Sen University

Other

Registry information

Official study title

Endocrine Fibroblast Growth Factor 19 and 21 Regulate the Insulin Resistance State in Gestational Diabetes Mellitus

Important dates

Study start
2013
Primary completion
2015
Study completion
2016
First posted
May 21, 2013
Registry last updated
May 30, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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