POST-LOAD PLASMA GLUCOSE INCREASE (PG-GAP) AS A RISK FACTOR FOR DEVELOPING DYSGLYCEMIA IN PATIENTS WITH TRANSFUSION-DEPENDENT Β-THALASSEMIA (Β-TDT): RETROSPECTIVE ANALYSIS OVER 8 YEARS Post load plasma glucose increase and the risk of glucose dysregulation in thalassemia
Main Article Content
Keywords
Transfusion-dependent β-thalassemia patients, oral glucose tolerance test, post-load plasma glucose gap, glucose dysregulation, risk factors
Abstract
Abstract. Background: Glucose dysregulation (GD) in transfusion-dependent β-thalassemia (β-TDT) patients demands early detection and intervention. However, current diagnostic criteria of patients with a normal oral glucose tolerance test (OGTT) may fail to detect all high-risk individuals.
Objectives: Our objective was to evaluate the incremental rise gap in plasma glucose (PG) during oral glucose tolerance tests (OGTTs), defined as the difference between 2h-PG and fasting PG, as a predictor for the future risk of developing glucose dysregulation (GD) and overt diabetes in patients with transfusion-dependent β-thalassemia (β-TDT) with normal glucose tolerance (NGT) .
Research design and methods: 58 β-TDT patients, recruited from three Thalassemia centers (Iran, Italy and Greece), were selected for the study. β-TDT patients were categorized into three groups, based on the difference between 2 h-PG and FPG (2 h-PG – FPG): "Low post-load", when the gap (2-h PG mg/dL - FPG ) was < 20th percentile ( < 10 mg/dL) Group A; "Medium post-load and High post-load" groups, when the differences was distributed between 20th and <75th centile (> 10 mg/dL and < 30 mg/dL (Group B). and ≥75th percentile ( ≥ 30 mg/dL; Group C.).
Results: In all 58 β-TDT patients, follow-up was available for 6-years and in 45 patients for 8 years within 2 years interval. The incidence of GD, [isolated high 1-h PG (>155 mg/dL) and Th-RD], after an 8-year follow-up, was significantly lower in Groups A and B (27/45 patients) compared to Group C (18/45 patients) (χ2: 4.8214;P:0.028). Noteworthy, three patients of group C ("High post-load gap") developed thalassemia-related diabetes mellitus (Th-RDM). At last evaluation in 13/45 (28.8%) patients the SF level was < 800 µg/L, in 17/45 (37.7%) between ≥ 800 µg/L and < 1,500 µg/L, in 14/45 (31,1 %) between ≥ 1,500 µg/L and < 3,000 µg/L, and in 1/45 (2.3%) ≥ 3,000 µg/L.
Conclusions: Our findings suggest that a high rise of postload plasma glucose gap, above 10 mg/dL, is associated with a progressively increased risk of glucose dysregulation over the next 6- 8-year period. These findings highlight the need for a personalized approach to assess the risk of early glucose metabolic disorders in β-TDT patients who are traditionally classified as normoglycemic.
Downloads
Abstract 24
PDF Downloads 9
HTML Downloads 5
References
2. Khamseh EM, Malek M, Hashemi-madani N, Ghassemi F, Rahimian N, Ziaee A,Foroughi-Gilvaee MR, Faranoush P, Sadighnia N, Elahinia A, Rezvany MR, Saeedi V, Faranoush M . Guideline for the diagnosis and treatment of diabetes mellitus in patients with transfusion-dependent thalassemia. Iran J Blood Cancer. 2023;15(4):293-303.https://doi.org/ not available.
3. World Health Organization. Classification of diabetes mellitus. Geneva: World Health Organization. 2019. p.1–36.
4. American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2021. Diabetes Care.2021;44 (Suppl 1):S15-S33. https://doi.org/10.2337/dc21-S002.
5. De Sanctis V, Soliman AT, Elsedfy H, AL Yaarubi S, Skordis N, Khater D, El Kholy M, Stoeva I, Fiscina B, Angastiniotis M, Daar S, Kattamis C. The ICET-A recommendations for the diagnosis and management of disturbances of glucose homeostasis in thalassemia major patients. Mediterr J Hematol Infect Dis. 2016; 8 (1): e2016058. https://doi.org/10.4084/mjhid.2016.058.
6. Farmakis D, Porter J, Taher A, Cappellini MD, Angastiniotis M, Eleftheriou A. 2021 Thalassaemia International Federation Guidelines for the Management of Transfusion-dependent Thalassemia. Hemasphere. 2022;6 (8):e732. https://doi.org/10.1097/HS9.0000000000000732.
7. De Sanctis V, Daar S, Soliman AT, Tzoulis P, Karimi M, Di Maio S, Kattamis C. Screening for glucose dysregulation in β-thalassemia major (β-TM): An update of current evidences and personal experience. Acta Biomed. 2022;93(1):e2022158. https://doi.org/10.23750/ abm.v93i1. 12802.
8. De Sanctis V, Canatan D, Daar S, Kattamis C, Banchev A, Modeva I, Savvidou I, Christou S, Kattamis A, Delaporta P, Kostaridou-Nikolopoulou S, Karimi M, Saki F, Faranoush M, Campisi S, Fortugno C, Gigliotti F, Wali Y, Al Yaarubi S, Yassin MA, Soliman AT, Kottahachchi D, Kurtoğlu E, Gorar S,Turkkahraman D, Unal S, Oymak Y,Tuncel AD, Karakas Z, Gül N, Yildiz M, Elhakim I, Tzoulis P. 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 adhension optimization. Mediterr J Hematol Infect Dis,2025:17 (1); e2025008; https://doi.org/10.4084/MJHID.2025.008.
9. Faranoush P, Elahinia A, Ziaee A, Faranoush M. Review of endocrine complications in transfusion-dependent thalassemia. Iran J Blood Cancer. 2023; 15(4):212-235. https://doi.org/ not available
10. Mahmoud AA, El-Hawy MA, Allam ET, Salem AH, Hola AS. HbA1c or fructosamine on evaluating glucose intolerance in children with beta- thalassemia. Pediatr Res. 2024;96 (5)1292-1298. https://doi.org/10. 1038/s41390-024-03146-y.
11. Dritsa M, EconomouM, Perifanis V, Teli A, Christoforidis A. Retrospective evaluation of oral glucose tolerance test in young patients with transfusion-dependent beta-thalassemia. Acta Haematol. 2025;148 (1):1–7. https://doi.org/10.1159/000523874.
12. Masrouri S, Tamehri Zadeh SS, Tohidi M, Azizi F, Hadaegh F. Linking extent of return to fasting state after oral glucose tolerance test to future risk of prediabetes and type 2 diabetes: Insights from the TLGS.J Diabetes Investig. 2024;15(12):1743-1752. https://doi.org/10.1111/jdi.14308.
13. WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser.1995;854:1-452. ISBN:92-4-120854-6.
14. Center for Disease Control and Prevention. Use and Interpretation of the WHO and CDC Growth Charts for Children from Birth to 20 Years in the United States 2014. Available online: https://www.cdc. gov/ nccdphp/dnpa/growth charts/resources/ growthchart.pdf (accessed on 1 February 2023).
15. American Diabetes Association Professional Practice Committee. 14. Children and adolescents: Standards of Care in Diabetes—2024. Diabetes Care. 2024;47(Suppl. 1):S258–S281.https://doi.org/ 10.2337/dc24-SDIS.
16. Fulwood R, Johnson CL, Bryner JD. Hematological and nutritional biochemistry reference data for persons 6 months–74 years of age: United States, 1976–1980. National Center for Health Statistics, Vital Health Stat Series.1982;11:p.1–173.
17. De Sanctis V, Soliman A, Tzoulis P, Daar S, Pozzobon GC, Kattamis C. A study of isolated hyperglycemia (blood glucose ≥155 mg/dL) at 1-hour of oral glucose tolerance test (OGTT) in patients with β-transfusion dependent thalassemia (β-TDT) followed for 12 years. Acta Biomed. 2021; 92(4): e2021322. https://doi.org/10.23750/abm.v92i4.11105.
18. Bergman M, Manco M, Satman I, Chan J, Inês Schmidt M, Sesti G, Vanessa Fiorentino T, Abdul-Ghani M, Jagannathan R, Kumar Thyparambil Aravindakshan P, Gabriel R, Mohan V, Buysschaert M, Bennakhi A, Pascal Kengne A, Dorcely B, Nilsson PM, Tuomi T, Battelino T, Hussain A, Ceriello A, Tuomilehto J. International Diabetes Federation Position Statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes. Diabetes Res Clin Pract. 2024:209:111589. https://doi.org/ 10.1016/j.diabres.2024.111589.
19. Alder R, Roesser EB. Introduction to probability and statistics. WH Freeman and Company Eds. Sixth Edition. San Francisco (USA).1977; p.1-426.
20. The Italian Data Protection Authority. Authorisation no. 9/2014—General Authorisation to Process Personal Data for Scientific Research Purposes. Available online: https://www.garanteprivacy.it/ web/ guest/home/ docweb/-/docweb-display/docweb/ 3786078 (accessed on 1 July 2023).
21. Abdul-Ghani MA, Williams K, DeFronzo R, Stern M. Risk of progression to type 2 diabetes based on relationship between postload plasma glucose and fasting plasma glucose. Diabetes Care. 2006; 29: 1613–1618. http://dx.doi.org/10.2337/dc05-1711.
22. Bartoli E, Fra GP,Carnevale Scianca GP. The oral glucose tolerance test (OGTT)revisited. Eur J Intern Med. 2011;22(1):8-12. http://dx.doi.org/10.1016/j.ejim.2010.07.008.
Article Sidebar
Article Details
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers. Authors will grant copyright of their articles to the Institute of Hematology, Catholic University, Rome . No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.