Fibroblast Growth Factors 19 and 21 in Gestational Diabetes Mellitus

July 26, 2022 updated by: Dongyu Wang, First Affiliated Hospital, Sun Yat-Sen University

Endocrine Fibroblast Growth Factor 19 and 21 Regulate the Insulin Resistance State 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • Obstetrics and Gynechology Department of the 1st affiliated hospital of Sun Yat-sen University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Study Population

university hospital

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: gestational diabetes mellitus
Those women (subjects) with gestational diabetes mellitus
Diagnostic test: biachemical detection

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.
Other: control
Those healthy pregnant women
Diagnostic test: biachemical detection

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The Concentration of Serum FGF19
Time Frame: in fasting state during 24-28 gestational weeks
in fasting state during 24-28 gestational weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Expression of FGF19 in Term Placenta
Time Frame: term delivery (when participants come back to hospital to give birth during 37-41 gestational weeks)
term delivery (when participants come back to hospital to give birth during 37-41 gestational weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital, Sun Yat-Sen University

Investigators

  • Study Director: Zilian Wang, M.D., PhD, Obstetrics and Gynechology Department of the 1st affiliated hospital of SYSU

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

May 16, 2013

First Submitted That Met QC Criteria

May 17, 2013

First Posted (Estimated)

May 21, 2013

Study Record Updates

Last Update Posted (Actual)

May 30, 2023

Last Update Submitted That Met QC Criteria

July 26, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5010dong

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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