FETUIN-A LEVELS AND THEIR RELATIONSHIP WITH INSULIN RESISTANCE AND LOW-GRADE INFLAMMATION
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Objective: This work was aimed to evaluate serum Fetuin-A levels and its probable association with insulin resistance and other relevant metabolic and inflammatory parameters in patients with insulin resistance (IR) and type 2 diabetes mellitus (T2DM). Method: A cross-sectional analytic study was carried out at Tikrit Teaching Hospital from August 2025 to January 2026. Two hundred and fifty subjects, 25–55 years in age were included in the study as follows – healthy (n = 50), insulin resistant but with no overt diabetes mellitus (n = 100) and type two diabetic patients with coexisting insulin resistance (T2D-IR, n = 100). The serum Fetuin-A level, fasting plasma glucose (FPG), fasting insulin, glycosylated hemoglobin (HbA1c), lipid profile, inflammatory markers including high sensitivity C-reactive protein (hs-CRP), IL-6 and TNF-α, as well as liver enzymes were determined. Insulin resistance was evaluated based on the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Results: The serum levels of Fetuin-A were significantly increased in both insulin resistant subjects with the highest level in type 2 diabetes mellitus patients (p < 0.001). Serum Fetuin-A levels were positively associated with HOMA-IR, fasting insulin, inflammatory parameters, triglycerides, body mass index and liver enzymes and inversely correlated with HDL-C. Novelty: The results of this study corroborate the potential value of Fetuin-A as a biomarker for metabolic disturbance and disease progression. High circulating levels of Fetuin-A strongly correlated with insulin resistance, chronic inflammation and metabolic profile unfavourability.
D. Accili, Z. Deng, and Q. Liu, “Insulin resistance in type 2 diabetes mellitus,” Nature Reviews Endocrinology, vol. 21, no. 7, pp. 413–426, 2025, doi: 10.1038/s41574-025-01114-y.
M. Apostolopoulou, V. Lambadiari, M. Roden, and G. D. Dimitriadis, “Insulin resistance in type 1 diabetes: Pathophysiological, clinical, and therapeutic relevance,” Endocrine Reviews, vol. 46, no. 3, pp. 317–348, 2025, doi: 10.1210/endrev/bnae032.
D. A. Mahmoud and S. S. Saleh, “Determination of the level of homocysteine and antioxidants in the blood serum of women with gestational diabetes,” Solid State Technology, vol. 64, no. 1, pp. 1129–1135, 2021.
Z. Wang, C. Yuan, T. Huang, and B. Lu, “Early nutritional interventions for chronic low-grade inflammation,” Trends in Endocrinology & Metabolism, 2025, doi: 10.1016/j.tem.2025.06.001.
B. Singh, A. Goyal, and B. C. Patel, “C-reactive protein: Clinical relevance and interpretation,” in StatPearls. Treasure Island, FL, USA: StatPearls Publishing, 2025.
E. M. M. Gkrinia and A. Belančić, “The mechanisms of chronic inflammation in obesity and potential therapeutic strategies: A narrative review,” Current Issues in Molecular Biology, vol. 47, no. 5, p. 357, 2025, doi: 10.3390/cimb47050357.
A. Z. K. Al-Quraghuli and D. A. Mahmood, “Determination of high-sensitivity C-reactive protein in chronic kidney disease patients in Al-Hawija General Hospital in Kirkuk City-Iraq,” International Journal of Biological and Pharmaceutical Sciences Archive, vol. 10, no. 1, pp. 173–187, 2025, doi: 10.53771/ijbpsa.2025.10.1.0068.
P. Iglesias, “The endocrine role of hepatokines: Implications for human health and disease,” Frontiers in Endocrinology, vol. 16, p. 1663353, 2025, doi: 10.3389/fendo.2025.1663353.
T. W. Jung, H. J. Yoo, and K. M. Choi, “Implication of hepatokines in metabolic disorders and cardiovascular diseases,” BBA Clinical, vol. 5, pp. 108–113, 2016, doi: 10.1016/j.bbacli.2016.03.002.
T. H. Kim, D.-G. Hong, and Y. M. Yang, “Hepatokines and non-alcoholic fatty liver disease: Linking liver pathophysiology to metabolism,” Biomedicines, vol. 9, no. 12, p. 1903, 2021, doi: 10.3390/biomedicines9121903.
M. Jemal et al., “The evolving roles of fetuin-A in type 2 diabetes mellitus and its potential clinical implications: A review,” Therapeutic Advances in Chronic Disease, vol. 16, p. 20406223251389795, 2025, doi: 10.1177/20406223251389795.
L. Bourebaba and K. Marycz, “Pathophysiological implication of fetuin-A glycoprotein in the development of metabolic disorders: A concise review,” Journal of Clinical Medicine, vol. 8, no. 12, p. 2033, 2019, doi: 10.3390/jcm8122033.
G. Ren et al., “American Journal of Physiology–Endocrinology and Metabolism,” American Journal of Physiology-Endocrinology and Metabolism, vol. 317, no. 2, pp. E250–E260, 2019.
H. A. Salman, F. K. Hussein, and S. J. Abdulrahman, “A comparison of glutathione and malondialdehyde concentrations in athletes engaged in certain sports,” Thamar University Journal of Natural & Applied Sciences, vol. 9, no. 1, pp. 39–42, 2024, doi: 10.59167/tujnas.v9i1.2053.
O. I. Gavril et al., “Fetuin-A as a link between dyslipidemia and cardiovascular risk in type 2 diabetes: A metabolic insight for clinical practice,” Biomedicines, vol. 13, no. 9, p. 2098, 2025, doi: 10.3390/biomedicines13092098.
K. Kulik-Kupka et al., “Fetuin-A and its association with anthropometric, atherogenic, and biochemical parameters and indices among women with polycystic ovary syndrome,” Nutrients, vol. 14, no. 19, p. 4034, 2022, doi: 10.3390/nu14194034.
M. Karajibani et al., “Serum fetuin-A and adipsin levels in type II diabetes patients,” International Journal of High Risk Behaviors and Addiction, vol. 8, no. 3, p. e91963, 2019, doi: 10.5812/ijhrba.91963.
Y. Wang, W.-P. Koh, M. K. Jensen, J.-M. Yuan, and A. Pan, “Plasma fetuin-A levels and risk of type 2 diabetes mellitus in a Chinese population: A nested case-control study,” Diabetes & Metabolism Journal, vol. 43, no. 4, pp. 474–486, 2019, doi: 10.4093/dmj.2018.0171.
M. C. Petersen and G. I. Shulman, “Mechanisms of insulin action and insulin resistance,” Physiological Reviews, vol. 98, no. 4, pp. 2133–2223, 2018, doi: 10.1152/physrev.00063.2017.
M. J. Honka et al., “Insulin-stimulated glucose uptake in skeletal muscle, adipose tissue and liver: A positron emission tomography study,” European Journal of Endocrinology, vol. 178, no. 5, pp. 523–531, 2018, doi: 10.1530/EJE-17-0882.
D. Pal et al., “Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance,” Nature Medicine, vol. 18, no. 8, pp. 1279–1285, 2012, doi: 10.1038/nm.2851.
D. Banerjee and A. Mani, “Obesity's systemic impact: Exploring molecular and physiological links to diabetes, cardiovascular disease, and heart failure,” Frontiers in Endocrinology, vol. 16, p. 1681766, 2025, doi: 10.3389/fendo.2025.1681766.
A. González-Périz et al., “Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: A role for resolvins and protectins,” FASEB Journal, vol. 23, no. 6, pp. 1946–1957, 2009, doi: 10.1096/fj.08-125674.
J. F. Trepanowski, J. Mey, and K. A. Varady, “Fetuin-A: A novel link between obesity and related complications,” International Journal of Obesity, vol. 39, no. 5, pp. 734–741, 2015, doi: 10.1038/ijo.2014.203.
Copyright (c) 2026 Rasha Jamal Khudhur, Reham Hassan Thamer, Aisha Salah Azeez
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