Original Articles
Vol. 18 No. 1 (2026): Mediterranean Journal of Hematology and Infectious Diseases

THE IMPACT OF PRE-ANALYTICAL FACTORS ON BLOOD GLUCOSE MEASUREMENTS AND  and recommendations THE IMPACT OF PRE-ANALYTICAL FACTORS ON BLOOD GLUCOSE MEASUREMENTS AND RECOMMENDATIONS  FOR CLINICAL PRACTICE: AN ICET-A MULTICENTER SURVEY IN TRANSFUSION-DEPENDENT Β THALASSEMIA (Β-TDT) PATIENTS

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Published: April 30, 2026
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Abstract. Background: During the last few decades, screening for dysglycemia in transfusion-dependent β-thalassemia patients (β-TDT) with an oral glucose tolerance test (OGTT) using fasting (FPG) and 2-hour plasma glucose (2h-PG) samples has been recommended at 10, 12, 14, and 16 years and annually thereafter. A precise measurement of blood glucose (BG) concentration is the mainstay for an accurate diagnosis of dysglycemia, in order to limit the risk of false-positive (i.e., overdiagnosis) and false-negative (i.e., underdiagnosis) results, especially in patients with BG values near the cut-off values.

Research objective: The primary objective of our survey was to describe the procedures followed during the pre-analytical phase of screening for dysglycemia, based on the actual clinical practice of Centers following β-TDT patients. Answers from the survey were compared with international recommendations (American Diabetes Association and World Health Organization).

Methods: This observational study was based on an online questionnaire survey.  All members of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) were officially invited. The questionnaire consisted of  6 sections and 22 questions, including single-choice, multiple-choice, and open-ended descriptive answers.

Results: 14 out of 18 invited Centers [Bulgaria, Cyprus, Greece, Iran (2), Italy (2), Oman, Qatar, Sri Lanka, Türkiye (3) and  United Kingdom] accepted and completed the survey promoted by the ICET-A with a response rate of  77.7 % The total number of β-TDT patients followed in the participating Centers was 3,372 and 2,932 (86.9 %) were over the age of 10 years. The total number of  thalassemia related diabetes mellitus (Th-RDM) reported by all Centers was 549. The total mean prevalence of  Th-RDM was 14.7 ± 10.2 % . Generally, the survey has shown that there was a variable adherence to, and deviations from, current international guidelines. The lowest adherence rate regarded the information and instructions given to patients prior to OGTT (~56%), and how the BG samples were stored from the time of collection to time of centrifugation and analysis (~80 %). Differences in  these factors may result in unintended variations in the prevalence of dysglycemia and have important implications for clinical practice.

Conclusions: Many factors across the total testing process (sample collection, storage and transport during the preanalytical phase) can significantly impact OGTT accuracy and reproducibility, especially in patients with blood glucose values closer to the cut-off values. To minimize pre-analytical errors, a more precise diagnostic approach associated with closer patient follow-up is  needed to reduce  the risk of errors in glucose measurement.

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References
1. 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
2. De Sanctis V, Canatan D, Daar S, Kattamis C. (Steering Committee); Banchev A, Modeva I, Savvidou I, Christou S, Kattamis A, Delaporta P, Kostaridou-Nikolopoulou S, Karim 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, Ay Tuncel D, Karakas Z, Gül N, Yildiz M, Elhakim I, Tzoulis P. (Participants). 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. Mediterr J Hematol Infect Dis. 2025, 17(1): e2025008. http://doi.org/10.4084/MJHID.2025.008
3.Tzoulis P, Yavropoulou MP, Banchev A, Modeva I, Daar S, De Sanctis V. Recent advancements in glucose dysregulation and pharmacological management of osteoporosis in transfusion-dependent thalassemia (TDT): an update of ICET-A (International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine). Acta Biomed. 2023;94(3)3:e2023178. http://doi.org/10.23750/ abm.v94i3.1480
4. American Diabetes Association Professional Practice Committee; 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2025. Diabetes Care. 2025; 48 (Supplement 1): S27–S49. https://doi.org/10.2337/dc25-S002
5. World Health Organization. Classification of diabetes mellitus. Geneva: World Health Organization. 2019. p.1-36. https://iris.who.int/ server/api/core/ bitstreams/ 2cb3ab68-a52a-402e-ad47-8bc5a4edc834/content
6. Bogdanet D, O'Shea P, Lyons C, Shafat A, Dunne F. The Oral Glucose Tolerance Test-Is It Time for a Change?-A Literature Review with an Emphasis on Pregnancy. J Clin Med. 2020; 9 (11):3451. https://doi.org/10.3390/jcm9113451
7.Sacks DB, Arnold M, Bakris GL, Bruns DE, Horvath AR, Lernmark Å, Metzger BE, Nathan DM, Kirkman MS. Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus. Diabetes Care. 2023;46(10):e151-e199. https://doi.org/10.2337/ dci23-0036
8 Mshelia DS, Adamu S, Galli RM. Oral glucose tolerance test (OGTT): Undeniably the first choice investigation of dysglycaemia, reproducibility can be improved.In: Type 2 Diabetes - From Pathophysiology to Cyber Systems. Intech Open. Ed.Anca Pantea Stoian. 2021:1-38.http://doi.org/10.5772/ intechopen. 96549
9. Bergman M, Manco M, Satman I, Chan J, Schmidt MI, 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
10. International Organization for Standardization. ISO 15189 - Medical Laboratories Requirements for Quality and Competence. 4th ed. Geneva: ISO, Ed., 2022
11. Plebani M. The detection and prevention of errors in laboratory medicine. Ann Clin Biochem. 2010; 47:101–110. https://doi.org/10.1258/acb.2009.009222
12.Klein KR, Walker CP, McFerren AL, Huffman H, Frohlich F, Buse JB. Carbohydrate intake prior to oral glucose tolerance testing. J Endocr Soc. 2021;5:bvab049. https://doi.org/10.1210/jendso/bvab049
13. Bogdanet D, O’Shea P, Lyons C, Shafat A, Dunne F. The Oral Glucose Tolerance Test—Is It Time for a Change ?—A Literature Review with an Emphasis on Pregnancy. J Clin Med. 2020; 9:3451. https://doi.org/ 10.3390/jcm9113451
14. Zubair M, Launico MV. Glucose tolerance test [Updated2025 Sept.15]. In: Statpearls [Internet] Available from: https//www.ncbi.nlm. nih.gov./books/ NBK532915/
15. Nevraumont A, Deltombe M, Bayart J L. How pre-analytical conditions impact glucose measurement and (gestational) diabetes diagnosis: A real-world stability study and a call for harmonization. Clin Chim Acta. 2024;562: 119875.https://doi.org/ 10.10167j.cca.2024.119875
16. Balboni F, Burbui S, Lippi G. Glucose variation in centrifuged serum and lithium-heparin gel tubes stored for up to 96 hours at room temperature or 4 °C. Scand J Clin Lab Invest. 2018;78:546-550. https://doi.org/10.1080/00365513.2018.1517221
17. Gambino R, Piscitelli J, Ackattupathil TA, Theriault JL, Andrin RD, Sanfilippo ML, Etienne M. Acidification of blood is superior to sodium fluoride alone as an inhibitor of glycolysis, Clin Chem. 2009; 55 (5):1019–1021, https://doi.org/10.1373/clinchem.2008.121707
18.Nevraumont A, Deltombe M, Bayart JL. How pre-analytical conditions impact glucose measurement and (gestational) diabetes diagnosis: A real-world stability study and a call for harmonization. Clin Chim Acta. 2024;562:119875. doi: 10.1016/j.cca.2024.119875
19. Gupta S, Kaur H.Inhibition of Glycolysis for Glucose Estimation in Plasma: Recent Guidelines and their Implications. Ind J Clin Biochem.2014;29 (2):262–264. https://doi. org/10.1007/s12291-013-0405-1
20. Grzych G, Defauwes I, de Tullio P, Pekar JD, Brousseau T, Lippi G, Cavalier E. Blood glucose measurement inside and outside the laboratory: both preanalytical and analytical challenges. Crit Rev Clin Lab Sci. 2025;62(8):613-630.http//doi.org/10.1080/10408363.2025.2533855
21. Pasqualetti S, Braga F, Panteghini M. Pre-analytical and analytical aspects affecting clinical reliability of plasma glucose results. Clin Biochem. 2017;50(10-11):587-594. http//doi.org/ doi: 10.1016/j.clinbiochem. 2017.03.009
22. Saracevic A, Dukic L, Juricic G, Milevoj Kopcinovic L, Mirosevic G, Simundic AM. Various glycolysis inhibitor-containingtubes for glucose measurement can not be used interchangeably due to clinically unacceptable biases betweent hem. Clin Chem Lab Med. 2018;56:236-241. https://doi.org/10.1515/cclm-2017-0279
23. Bonetti G, Giavarina D, Carta M. Clinical impact of citrate- containing tubes on the detection of glucose abnormalities by the oral glucose tolerance test. Diagnosis (Berl). 2019;6:377-383. https://doi.org/10. 1515/ dx-2018-0100
24. Pasqualetti S, Panteghini M. Clinical impact of glycolysis inhibition on plasma glucose results requires caution. Ann Clin Biochem. 2017;54:302-303. https://doi.org/10.1177/0004563216659091
25. Rebekah Carey R, Lunt H, Heenan HF, Frampton CMA, Florkowski CM. Collection tubes containing citrate stabiliser over-estimate plasma glucose, when compared to other samples undergoing immediate plasma separation. Clin Biochem.2016; 49:1406–1411. http://doi.org/10.1016/j.clinbiochem.2016.05.017
26. Pintaudi B, Di Vieste G, D’Anna R, Chiereghin F, Biamonte E, Corrado F, Di Benedetto A. The analytical reliability of the oral glucose tolerance test for the diagnosis of gestational diabetes: An observational, retrospective study in a caucasian population. J Clin Med. 2022;11:564. https:// doi.org/10. 3390/jcm11030564

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Blood measurement in thalassemia

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“THE IMPACT OF PRE-ANALYTICAL FACTORS ON BLOOD GLUCOSE MEASUREMENTS AND  and recommendations THE IMPACT OF PRE-ANALYTICAL FACTORS ON BLOOD GLUCOSE MEASUREMENTS AND RECOMMENDATIONS  FOR CLINICAL PRACTICE: AN ICET-A MULTICENTER SURVEY IN TRANSFUSION-DEPENDENT Β THALASSEMIA (Β-TDT) PATIENTS” (2026) Mediterranean Journal of Hematology and Infectious Diseases, 18(1). doi:10.4084/MJHID.2026.035.