Interleukin 6 as a key inflammatory predictor of gestational diabetes – clinical and biochemical evidence

Authors

  • Sadiq Hassan Hadi Department of Medical Laboratory Techniques, College of Health and Medical Techniques, Kufa, Al-Furat Al-Awsat Technical University, Al-Kufa, Iraq https://orcid.org/0009-0009-0599-3017
  • Abdul-Samad Uleiwi Hassan Department of Medical Laboratory Techniques, College of Health and Medical Techniques, Kufa, Al-Furat Al-Awsat Technical University, Al-Kufa, Iraq https://orcid.org/0000-0003-2957-4641
  • Redha Dawud Abdalredha Department of Medical Laboratory Techniques, College of Health and Medical Techniques, Kufa, Al-Furat Al-Awsat Technical University, Al-Kufa, Iraq https://orcid.org/0009-0005-6774-5036

DOI:

https://doi.org/10.15584/ejcem.2025.3.17

Keywords:

gestational diabetes mellitus, insulin resistance, interleukin-6, maternal inflammation, metabolic dysregulation, pregnancy complications

Abstract

Introduction and aim. Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder in pregnancy associated with significant maternal and fetal complications. Chronic low-grade inflammation is increasingly recognized as a key contributor to GDM pathophysiology, with interleukin 6 (IL-6) emerging as an important mediator of insulin resistance. The aim was to investigate the relationship between IL-6 levels and metabolic parameters in pregnant women with and without GDM, and to evaluate the diagnostic performance of IL-6 for distinguishing GDM.

Material and methods. A total of 45 pregnant women with GDM and 45 normoglycemic controls between 24 and 28 weeks of gestation were enrolled. Clinical data age, body mass index (BMI), gestational age, fasting insulin, oral glucose tolerance test (OGTT), and lipid profile were assessed. IL-6 was quantified by high-sensitivity enzyme-linked immunosorbent assay. Correlation analysis, multiple linear regression, and receiver operating characteristic (ROC) curve analysis were performed using SPSS.

Results. Women with GDM exhibited significantly higher IL-6 levels (25.35±11.76 ng/L) than controls (11.02±3.59 ng/L, p<0.001). IL-6 showed strong positive correlations with fasting insulin (r=0.900, p<0.001) and OGTT (r=0.684, p<0.001). Multiple regression indicated that gestational age, BMI, and total cholesterol were significant predictors of IL-6 in GDM (p<0.05). ROC analysis revealed an area under the curve of 0.923 (p<0.001) for IL-6, with a sensitivity of 88.9% and specificity of 78.3% at the cutoff of 13.243 ng/L.

Conclusion. Elevated IL-6 is strongly associated with insulin resistance and dyslipidemia in GDM, suggesting a potential role as an inflammatory biomarker for early risk stratification. Incorporating IL-6 measurement into GDM screening protocols may enhance diagnostic accuracy and facilitate timely interventions to improve pregnancy outcomes.

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References

Lee J, Lee NK, Moon JH. Gestational Diabetes Mellitus: Mechanisms Underlying Maternal and Fetal Complications. Endocrinol Metab (Seoul). 2025;40(1):10-25. doi: 10.3803/EnM.2024.2264

Avilez RG, Ponti L, Gabini S, Camats S. Impact of Gestational Diabetes on Maternal and Fetal Health: Prevalence, Risks and Interdisciplinary Treatment. SCT Proceedings in Interdisciplinary Insights and Innovations. 2025;3:481.

Zgutka K, Tkacz M, Tomasiak P, et al. Gestational Diabetes Mellitus-Induced Inflammation in the Placenta via IL-1β and Toll-like Receptor Pathways. Int J Mol Sci. 2024;25(21):11409. doi: 10.3390/ijms252111409

Taneera J, Khalique A, Mohammed AK, et al. Investigating the impact of IL6 on insulin secretion: evidence from INS-1 Cells, human pancreatic islets, and serum analysis. Cells. 2024;13(8):685. doi: 10.3390/cells13080685

Pioch A, Markwitz W, Litwin A, Szpera A. Inteleukin-6 secretion during pathophysiological events of pregnancy–preterm birth, preeclampsia, fetal growth restriction, gestational diabetes mellitus. J Med Sci. 2024;93(2):e984-e984. doi: 10.20883/medical.e984

Sakamoto K, Butera MA, Zhou C, et al. Overnutrition causes insulin resistance and metabolic disorder through increased sympathetic nervous system activity. Cell Metab. 2025;37(1):121-137. doi: 10.1016/j.cmet.2024.09.012

Giraldez MD, Carneros D, Garbers C, Rose-John S, Bustos M. New insights into IL-6 family cytokines in metabolism, hepatology and gastroenterology. Nat Rev Gastroenterol Hepatol. 2021;18(11):787-803. doi: 10.1038/s41575-021-00473-x

Azeez DD, AlKatib SR, Aziz ND. Exploring Interleukin 6 as a Promising Marker for The Diagnosis of Gestational Diabetes Mellitus. Karbala Journal of Pharmaceutical Sciences. 2023;14(23):106-115. doi: 10.62472/kjps.v14.i23.106-115

Shrestha B, Dunn L. The declaration of Helsinki on medical research involving human subjects: a review of seventh revision. 2019; doi:10.33314/jnhrc.v17i4.1042

Luo J, Tong L, Xu A, et al. Gestational Diabetes Mellitus: New Thinking on Diagnostic Criteria. Life. 2024;14(12):1665. doi: 10.3390/life14121665

Zhang X, Hartmann P. How to calculate sample size in animal and human studies. Frontiers in Medicine. 2023;10:215927. doi: 10.3389/fmed.2023.1215927

Inamdar A. Correlation Of Body Mass Index (BMI) With Systolic And Diastolic Blood Pressure In Rural Indian Patients. Journal of Hypertension. 2024;42(1):e227-e228. Doi: 10.1097/01.hjh.0001021788.95421.3f

Sullivan LM. Essentials of biostatistics in public health. Jones & Bartlett Learning; 2023.

Visiedo F, Vázquez-Fonseca L, Ábalos-Martínez J, et al. Maternal elevated inflammation impairs placental fatty acids β-oxidation in women with gestational diabetes mellitus. Front Endocrinol. 2023;14:1146574. doi: 10.3389/fendo.2023.1146574

McElwain C, McCarthy F, McCarthy C. Gestational Diabetes Mellitus and Maternal Immune Dysregulation: What We Know So Far. Int J Mol Sci. 2021;22(8):4261. doi: 10.3390/ijms22084261

Musumeci A, McElwain CJ, Manna S, McCarthy F, McCarthy C. Exposure to gestational diabetes mellitus increases subclinical inflammation mediated in part by obesity. Clin Exp Immunol. 2024;216(3):280-292. doi: 10.1093/cei/uxae010

Liu Y, Chen Y, Lin Y, Wei B, Luo Z. Impacts of pro‐inflammatory cytokines variant on cardiometabolic profile and premature coronary artery disease: A systematic review and meta‐analysis. J Cell Mol Med. 2024;28(8):e18311. Doi: 10.1111/jcmm.18311

Saucedo R, Ortega-Camarillo C, Ferreira-Hermosillo A, Díaz-Velázquez MF, Meixueiro-Calderón C, Valencia-Ortega J. Role of oxidative stress and inflammation in gestational diabetes mellitus. Antioxidants. 2023;12(10):1812. doi: 10.3390/antiox12101812

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Published

2025-09-30

How to Cite

Hadi, S. H., Hassan, A.-S. U., & Abdalredha, R. D. (2025). Interleukin 6 as a key inflammatory predictor of gestational diabetes – clinical and biochemical evidence. European Journal of Clinical and Experimental Medicine, 23(3), 633–640. https://doi.org/10.15584/ejcem.2025.3.17

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ORIGINAL PAPERS