Intermediate Hyperglycemia and its Association with Iron Chelation Therapy in Children with Transfusion-Dependent Beta-Thalassemia in Kirkuk, Iraq
Keywords:
beta-thalassemia, hyperglycemia, iron chelation, OGT, IraqAbstract
Background: Iron overload in transfusion-dependent β-thalassemia (TDT) disrupts pancreatic β-cell function, predisposing children to intermediate hyperglycemia.
Methods: A cross-sectional study of 150 Iraqi children with TDT assessed glycemic status using fasting plasma glucose and OGTT. Clinical and laboratory variables were compared between normoglycaemic and hyperglycemic groups.
Results: Intermediate hyperglycemia was detected in 28 patients (18.5%): 15 with isolated IGT and 13 with isolated IFG. Older age was significantly associated with hyperglycemia (14.8 ± 4.5 vs. 11.8 ± 4.9 years; p = 0.01). Irregular chelation therapy showed the strongest modifiable association 29.1% of irregularly chelated children had hyperglycemia versus 11.4% of regularly chelated children (p = 0.007). No significant associations were found for gender, BMI, ferritin, chelation type, or viral hepatitis.
Conclusion: Intermediate hyperglycemia affects 18.5% of Iraqi children with TDT. Chelation adherence is the key modifiable risk factor, supporting routine OGTT screening from age 10 years.
References
[1] A. Kattamis, J. L. Kwiatkowski, and Y. Aydinok, “Thalassaemia,” Lancet, vol. 399, no. 10343, pp. 2310–2324, 2022, doi: 10.1016/S0140-6736(22)00536-0.
[2] K. A. Kadhim, K. H. Baldawi, and F. H. Lami, “Prevalence, incidence, trend, and complications of thalassemia in Iraq,” Hemoglobin, vol. 41, no. 3, pp. 164–168, 2017, doi: 10.1080/03630269.2017.1354877.
[3] R. K. Lafta, R. Sadiq, and Z. Muhammed, “Burden of thalassemia in Iraq,” Public Health Open Access, vol. 7, no. 1, Art. no. 000242, 2023, doi: 10.23880/phoa-16000242.
[4] G. L. Forni, B. Gianesin, K. M. Musallam, F. Longo, R. Rosso, R. Lisi, et al., “Overall and complication-free survival in a large cohort of patients with β-thalassemia major followed over 50 years,” American Journal of Hematology, vol. 98, no. 3, pp. 381–387, 2023, doi: 10.1002/ajh.26798.
[5] J. L. Kwiatkowski, “Clinical challenges with iron chelation in beta thalassemia,” Hematology/Oncology Clinics of North America, vol. 37, no. 2, pp. 379–391, 2023, doi: 10.1016/j.hoc.2022.12.013.
[6] A. Adramerina and M. Economou, “Challenges of iron chelation in thalassemic children,” Thalassemia Reports, vol. 14, no. 1, pp. 1–9, 2024, doi: 10.3390/thalassrep14010001.
[7] G. L. Forni, A. Kattamis, K. H. M. Kuo, A. Maggio, S. Sheth, A. T. Taher, et al., “Iron chelation therapy for children with transfusion-dependent β-thalassemia: How young is too young?” Pediatric Blood & Cancer, vol. 71, no. 8, Art. no. e31035, 2024, doi: 10.1002/pbc.31035.
[8] V. De Sanctis, S. Daar, A. T. Soliman, P. Tzoulis, M. Karimi, S. Di Maio, et al., “Screening for glucose dysregulation in β-thalassemia major (β-TM): An update of current evidences and personal experience,” Acta Biomedica, vol. 93, no. 1, Art. no. e2022158, 2022, doi: 10.23750/abm.v93i1.12802.
[9] American Diabetes Association Professional Practice Committee, “2. Diagnosis and classification of diabetes: Standards of Care in Diabetes—2024,” Diabetes Care, vol. 47, suppl. 1, pp. S20–S42, 2024, doi: 10.2337/dc24-S002.
[10] I. M. Almusawi, M. H. Alaraji, and A. A. Hasan, “Epidemiology of B. thalassemia in Karbala city, Iraq,” IJPPR Human, vol. 25, no. 1, pp. 17–32, 2022.
[11] B. A. Zaman, Z. R. Mustafa, D. A. Mohamed, H. A. Aswad, and D. M. Abdulah, “Epidemiological and clinical profile of hemoglobinopathies and thalassemia in Duhok, Kurdistan Region of Iraq: A retrospective study,” Thalassemia Reports, vol. 15, no. 4, Art. no. 12, 2025, doi: 10.3390/thalassrep15040012.
[12] J. Taneera, E. Mahgoub, R. Qannita, A. Alalami, O. A. Shehadat, M. Youssef, et al., “β-Thalassemia and diabetes mellitus: Current state and future directions,” Hormone and Metabolic Research, vol. 56, no. 4, pp. 272–278, 2023, doi: 10.1055/a-2185-5073.
[13] J. Huang, J. Shen, Q. Yang, Z. Cheng, X. Chen, T. Yu, et al., “Quantification of pancreatic iron overload and fat infiltration and their correlation with glucose disturbance in pediatric thalassemia major patients,” Quantitative Imaging in Medicine and Surgery, vol. 11, no. 2, pp. 665–675, 2021, doi: 10.21037/qims-20-292.
[14] V. De Sanctis, A. Soliman, P. Tzoulis, S. Daar, G. C. Pozzobon, and C. Kattamis, “A study of isolated hyperglycemia (blood glucose ≥155 mg/dL) at 1-hour of OGTT in patients with β-TDT followed for 12 years,” Acta Biomedica, vol. 92, no. 4, Art. no. e2021322, 2021, doi: 10.23750/abm.v92i4.11105.
[15] A. El-Beshlawy, H. Dewedar, S. Hindawi, S. Alkindi, A. A. Tantawy, M. A. Yassin, et al., “Management of transfusion-dependent β-thalassemia (TDT): Expert insights and practical overview from the Middle East,” Blood Reviews, vol. 63, Art. no. 101138, 2024, doi: 10.1016/j.blre.2023.101138.
[16] V. De Sanctis, D. Canatan, S. Daar, C. Kattamis, A. Banchev, I. Modeva, et al., “A multicenter ICET-A survey on adherence to annual oral glucose tolerance test (OGTT) screening in transfusion-dependent thalassemia (TDT) patients—The expert clinicians' opinion on factors influencing the adherence and on alternative strategies for adherence optimization,” Mediterranean Journal of Hematology and Infectious Diseases, vol. 17, no. 1, Art. no. e2025008, 2025, doi: 10.4084/MJHID.2025.008.
[17] M. Rasel, M. F. Hashmi, and S. K. Mahboobi, “Transfusion iron overload,” StatPearls [Internet]. Treasure Island, FL, USA: StatPearls Publishing, 2026.
[18] S. Campisi, V. De Sanctis, A. Soliman, S. Daar, and C. Kattamis, “The credibility of intermediate hyperglycemia (IH) at one hour of OGTT in 30 β-thalassemia patients (β-thal) with persistent low iron overload,” Acta Biomedica, vol. 95, no. 4, Art. no. e2024137, 2024, doi: 10.23750/abm.v95i4.16137.
[19] A. A. Mezher and W. K. Ali, “Indicators of blood glucose imbalance in children with beta thalassemia major,” Academic International Journal of Medical Sciences, vol. 1, no. 2, pp. 35–42, 2024, doi: 10.59675/M213.
[20] T. Keowmani, S. C. Teo, K. C. Yap, W. L. Chua, N. F. Mohd Tahir, P. W. Chua, V. C. Lim, and H. H. Leong, “Adherence to iron chelation therapy among children with beta thalassemia major: A multicenter cross-sectional study,” Hemoglobin, vol. 47, no. 6, pp. 237–244, 2023, doi: 10.1080/03630269.2023.2295291.
[21] P. S. Reddy, M. Locke, and S. M. Badawy, “A systematic review of adherence to iron chelation therapy among children and adolescents with thalassemia,” Annals of Medicine, vol. 54, no. 1, pp. 326–342, 2022, doi: 10.1080/07853890.2022.2028894.
[22] W. J. Lee, N. A. Mohd Tahir, G. Y. Chun, and S. C. Li, “The impact of chelation compliance in health outcome and health related quality of life in thalassaemia patients: A systematic review,” Health and Quality of Life Outcomes, vol. 22, no. 1, Art. no. 14, 2024, doi: 10.1186/s12955-023-02221-y.
[23] M. Pines, D. Kleinert, C. Thomas, et al., “Real-world experience with iron chelation therapy in transfusion-dependent thalassemia: Impact of the oral chelators' era,” Annals of Hematology, vol. 103, no. 12, pp. 5229–5234, 2024, doi: 10.1007/s00277-024-06092-1.
[24] E. Dewiyanti, A. Aditiawati, and D. P. Sari, “Serum ferritin levels and endocrine disorders in children with thalassemia major,” Paediatrica Indonesiana, vol. 61, no. 3, pp. 125–132, 2021, doi: 10.14238/pi61.3.2021.125-32.
[25] A. Meloni, L. Pistoia, M. C. Putti, F. Longo, E. Corigliano, P. Ricchi, “Pancreatic iron in pediatric transfusion-dependent beta-thalassemia patients: A longitudinal MRI study,” Pediatric Blood & Cancer, vol. 71, no. 5, Art. no. e30923, 2024, doi: 10.1002/pbc.30923.
[26] İ. İncefidan, E. G. Kazancı, D. Güven, and Ö. Kara, “Association between iron overload and glucose metabolism in children and youth with transfusion-dependent beta thalassemia: The role of chelation therapy,” Mediterranean Journal of Hematology and Infectious Diseases, vol. 18, no. 1, Art. no. e2026017, 2026, doi: 10.4084/MJHID.2026.017.
[27] A. A. Mahmoud, M. A. El-Hawy, E. T. Allam, et al., “HbA1c or fructosamine on evaluating glucose intolerance in children with beta-thalassemia,” Pediatric Research, vol. 96, pp. 1292–1298, 2024, doi: 10.1038/s41390-024-03146-y.
[28] A. K. Khare, K. P. Patel, K. Singh, and A. Paliwal, “Study of thalassemia in pediatrics population,” International Journal of Community Medicine and Public Health, vol. 11, no. 10, pp. 3859–3864, 2024, doi: 10.18203/2394-6040.ijcmph20242865.
