The Role of IL-6 and TNF-α as Early Biomarkers in the Prediction and Diagnosis of Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) occurs in approximately 9–25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first recognition durin...

Full description

Saved in:
Bibliographic Details
Main Authors: Antonia Varthaliti, Vasilios Lygizos, Maria Fanaki, Vasilios Pergialiotis, Angeliki Papapanagiotou, Kalliopi Pappa, Marianna Theodora, Maria Anastasia Daskalaki, Panos Antsaklis, George Daskalakis
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/13/7/1627
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849407705046843392
author Antonia Varthaliti
Vasilios Lygizos
Maria Fanaki
Vasilios Pergialiotis
Angeliki Papapanagiotou
Kalliopi Pappa
Marianna Theodora
Maria Anastasia Daskalaki
Panos Antsaklis
George Daskalakis
author_facet Antonia Varthaliti
Vasilios Lygizos
Maria Fanaki
Vasilios Pergialiotis
Angeliki Papapanagiotou
Kalliopi Pappa
Marianna Theodora
Maria Anastasia Daskalaki
Panos Antsaklis
George Daskalakis
author_sort Antonia Varthaliti
collection DOAJ
description Gestational diabetes mellitus (GDM) occurs in approximately 9–25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first recognition during pregnancy and is a multifactorial condition with a pathophysiology that remains incompletely understood. It is strongly associated with a chronic low-grade inflammatory state that contributes to insulin resistance, a hallmark of GDM pathogenesis. Among the fundamental pro-inflammatory cytokines implicated in this process, TNF-α and IL-6 play central roles. TNF-α is a cytokine primarily secreted by activated macrophages, as well as by adipocytes in the context of obesity. Many studies have shown that its levels are elevated in pregnant women with GDM compared to normoglycemic pregnant individuals. IL-6 is another pro-inflammatory cytokine secreted by immune cells, adipose tissue, and the placenta. It is found in higher concentrations in the maternal circulation during pregnancies complicated by GDM. Both TNF-α and IL-6 act synergistically to perpetuate a pro-inflammatory intrauterine environment. Their combined effects exacerbate insulin resistance and may impair pancreatic β-cell compensation during pregnancy, facilitating the onset of GDM in genetically or metabolically susceptible individuals. Recent research has identified various maternal serum biomarkers, such as TNF-α and IL-6, that may hold promise for the early detection of GDM. The aim of our study is to evaluate whether TNF-α and IL-6 can be used as diagnostic tools for the early diagnosis of GDM, allowing for timely intervention and reducing the risk of associated maternal and fetal complications.
format Article
id doaj-art-305534fe64a548a89732fe31dcf65432
institution Kabale University
issn 2227-9059
language English
publishDate 2025-07-01
publisher MDPI AG
record_format Article
series Biomedicines
spelling doaj-art-305534fe64a548a89732fe31dcf654322025-08-20T03:35:58ZengMDPI AGBiomedicines2227-90592025-07-01137162710.3390/biomedicines13071627The Role of IL-6 and TNF-α as Early Biomarkers in the Prediction and Diagnosis of Gestational Diabetes MellitusAntonia Varthaliti0Vasilios Lygizos1Maria Fanaki2Vasilios Pergialiotis3Angeliki Papapanagiotou4Kalliopi Pappa5Marianna Theodora6Maria Anastasia Daskalaki7Panos Antsaklis8George Daskalakis91st Department of Obstetrics and Gynecology, “Alexandra” General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece1st Department of Obstetrics and Gynecology, “Alexandra” General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece1st Department of Obstetrics and Gynecology, “Alexandra” General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece1st Department of Obstetrics and Gynecology, “Alexandra” General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, GreeceDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece1st Department of Obstetrics and Gynecology, “Alexandra” General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece1st Department of Obstetrics and Gynecology, “Alexandra” General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece1st Department of Obstetrics and Gynecology, “Alexandra” General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece1st Department of Obstetrics and Gynecology, “Alexandra” General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece1st Department of Obstetrics and Gynecology, “Alexandra” General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, GreeceGestational diabetes mellitus (GDM) occurs in approximately 9–25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first recognition during pregnancy and is a multifactorial condition with a pathophysiology that remains incompletely understood. It is strongly associated with a chronic low-grade inflammatory state that contributes to insulin resistance, a hallmark of GDM pathogenesis. Among the fundamental pro-inflammatory cytokines implicated in this process, TNF-α and IL-6 play central roles. TNF-α is a cytokine primarily secreted by activated macrophages, as well as by adipocytes in the context of obesity. Many studies have shown that its levels are elevated in pregnant women with GDM compared to normoglycemic pregnant individuals. IL-6 is another pro-inflammatory cytokine secreted by immune cells, adipose tissue, and the placenta. It is found in higher concentrations in the maternal circulation during pregnancies complicated by GDM. Both TNF-α and IL-6 act synergistically to perpetuate a pro-inflammatory intrauterine environment. Their combined effects exacerbate insulin resistance and may impair pancreatic β-cell compensation during pregnancy, facilitating the onset of GDM in genetically or metabolically susceptible individuals. Recent research has identified various maternal serum biomarkers, such as TNF-α and IL-6, that may hold promise for the early detection of GDM. The aim of our study is to evaluate whether TNF-α and IL-6 can be used as diagnostic tools for the early diagnosis of GDM, allowing for timely intervention and reducing the risk of associated maternal and fetal complications.https://www.mdpi.com/2227-9059/13/7/1627gestational diabetes mellitusdiagnosisbiomarkersIL-6TNF-αpregnancy
spellingShingle Antonia Varthaliti
Vasilios Lygizos
Maria Fanaki
Vasilios Pergialiotis
Angeliki Papapanagiotou
Kalliopi Pappa
Marianna Theodora
Maria Anastasia Daskalaki
Panos Antsaklis
George Daskalakis
The Role of IL-6 and TNF-α as Early Biomarkers in the Prediction and Diagnosis of Gestational Diabetes Mellitus
Biomedicines
gestational diabetes mellitus
diagnosis
biomarkers
IL-6
TNF-α
pregnancy
title The Role of IL-6 and TNF-α as Early Biomarkers in the Prediction and Diagnosis of Gestational Diabetes Mellitus
title_full The Role of IL-6 and TNF-α as Early Biomarkers in the Prediction and Diagnosis of Gestational Diabetes Mellitus
title_fullStr The Role of IL-6 and TNF-α as Early Biomarkers in the Prediction and Diagnosis of Gestational Diabetes Mellitus
title_full_unstemmed The Role of IL-6 and TNF-α as Early Biomarkers in the Prediction and Diagnosis of Gestational Diabetes Mellitus
title_short The Role of IL-6 and TNF-α as Early Biomarkers in the Prediction and Diagnosis of Gestational Diabetes Mellitus
title_sort role of il 6 and tnf α as early biomarkers in the prediction and diagnosis of gestational diabetes mellitus
topic gestational diabetes mellitus
diagnosis
biomarkers
IL-6
TNF-α
pregnancy
url https://www.mdpi.com/2227-9059/13/7/1627
work_keys_str_mv AT antoniavarthaliti theroleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT vasilioslygizos theroleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT mariafanaki theroleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT vasiliospergialiotis theroleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT angelikipapapanagiotou theroleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT kalliopipappa theroleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT mariannatheodora theroleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT mariaanastasiadaskalaki theroleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT panosantsaklis theroleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT georgedaskalakis theroleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT antoniavarthaliti roleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT vasilioslygizos roleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT mariafanaki roleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT vasiliospergialiotis roleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT angelikipapapanagiotou roleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT kalliopipappa roleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT mariannatheodora roleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT mariaanastasiadaskalaki roleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT panosantsaklis roleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus
AT georgedaskalakis roleofil6andtnfaasearlybiomarkersinthepredictionanddiagnosisofgestationaldiabetesmellitus