Fibroblast Growth Factors 19 and 21 in Gestational Diabetes Mellitus

Gestational Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01858597
• Other study ID #: 5010dong
• Status: Completed
• Phase: N/A
• Start date: March 2013
• Est. completion date: March 2016

Study information

• Verified date: July 2022
• Source: First Affiliated Hospital, Sun Yat-Sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: March 2016
• Est. primary completion date: March 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes, Gestational
• Gestational Diabetes Mellitus

Intervention

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 ßKlotho(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.

Locations

Country	Name	City	State
China	Obstetrics and Gynechology Department of the 1st affiliated hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital, Sun Yat-Sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Concentration of Serum FGF19		in fasting state during 24-28 gestational weeks
Secondary	Expression of FGF19 in Term Placenta		term delivery (when participants come back to hospital to give birth during 37-41 gestational weeks)