Screening for glucose dysregulation in β-thalassemia major (β-TM): An update of current evidences and personal experience Screening for glucose dysregulation in β-thalassemia major

Main Article Content

Vincenzo De Sanctis
Shahina Daar
Ashraf T Soliman
Ploutarchos Tzoulis
Mehran Karimi
Salvatore Di Maio
Christos Kattamis

Keywords

β-thalassemia major, glucose dysregulation, prediabetes, screening

Abstract

Abstract. Glucose dysregulation (GD) in patients with β-thalassemia major (β-TM) usually develops gradually. Prediabetes consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), the latter detected by a standardized oral glucose tolerance test (OGTT). Diagnosis of prediabetes is essential for an early identification of high-risk individuals who will benefit from intensive iron chelation therapy and lifestyle modification. Therefore, patients with β-TM should undergo annual screening for glucose abnormalities, according to international recommendations, starting from the age of 10 years. OGTT remains the preferred screening method as it is more sensitive for GD than fasting plasma glucose (FPG), although it is poorly reproducible. The use of HbA1c measurement has limited use as it is generally considered unreliable in patients with thalassemia. Continuous glucose monitoring system (CGMS) is an accurate method to detect the variability of glucose fluctuations and offers the opportunity for better assessment of glucose homeostasis in a selected group of β-TM patients. Pancreatic Magnetic Resonance Imaging (MRI) associated with insulin secretion-sensitivity index-2 (ISSI-2) could be a complementary test, minimizing the necessity for OGTT and identifying high-risk patients before irreversible pancreatic damage occurs. The aims of this short report are to give practical guidance for an early identification of GD in β-TM patients, to summarise our experience, and to offer an impetus for further research in the field.

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References

1. Ang AL, Tzoulis P, Prescott E, Davis BA, Barnard M, Shah FT. History of myocardial iron loading is a strong risk factor for diabetes mellitus and hypogonadism in adults with β thalassemia major. Eur J Haematol 2014;92:229-36.
2. Liang Y, Bajoria R, Jiang Y, Su H, Pan H, Xia N, et al. Prevalence of diabetes mellitus in Chinese children with thalassaemia major. Trop Med Int Health 2017;22:716-24.
3 Gomber S, Dabas A, Bagmar S, Madhu SV. Glucose Homeostasis and Effect of Chelation on β Cell Function in Children With β-Thalassemia Major. J Pediatr Hematol Oncol 2018;40:56-9.
4. He LN, Chen W, Yang Y, Xie YJ, Xiong ZY, Chen DY, et al. Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients with β-Thalassemia Major: A Meta-Analysis. Biomed Res Int 2019;2019:6573497.
5. De Sanctis V, Soliman A, Tzoulis P, Daar S, Kattamis A, Delaporta P, et al. The Prevalence of glucose dysregulations (GDs) in patients with β-thalassemias in different countries: A preliminary ICET-A survey. Acta Biomed 2021;92(3):e2021240.
6. De Sanctis V, Soliman A, Tzoulis P, Daar S, Fiscina B, Kattamis C. The Pancreatic changes affecting glucose homeostasis in transfusion dependent β- thalassemia (TDT): a short review. Acta Biomed 2021;92(3):e2021232.
7. De Sanctis V, Soliman AT, Tzoulis P, Daar S, Di Maio S, Fiscina B, et al. Glucose Metabolism and Insulin Response to Oral Glucose Tolerance Test (OGTT) in Prepubertal Patients with Transfusion-Dependent β-thalassemia (TDT): A Long-Term Retrospective Analysis. Mediterr J Hematol Infect Dis 2021;13(1): e2021051.
8. Berdoukas V, Nord A, Carson S, Puliyel M, Hofstra T, Wood J, et al. Tissue iron evaluation in chronically transfused children shows significant levels of iron loading at a very young age. Am J Hematol 2013;88: E 283-5.
9. Nimkarn N, Songdej D, Dumrongwongsiri O, Sirachainan N, Chuansumrit A; Thalassemia Study Group. Age as a major factor associated with zinc and copper deficiencies in pediatric thalassemia. J Trace Elem Med Biol 2021;68:126817.
10. Fung EB, Gildengorin G, Talwar S, Hagar L, Lal A. Zinc status affects glucose homeostasis and insulin secretion in patients with thalassemia. Nutrients 2015;7:4296–307.
11. Himoto T, Masaki T. Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with Chronic Liver Disease. Nutrients 2018;10(1):88.
12. De Sanctis V, Soliman AT, Elsedfy H, Yaarubi SA, Skordis N, Khater D, et al. 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.
13. Corrao S, Nobili A, Natoli G, Mannucci PM, Perticone F, Pietrangelo A, Argano C; REPOSI Investigators. Hyperglycemia at admission, comorbidities, and in-hospital mortality in elderly patients hospitalized in internal medicine wards: data from the RePoSI Registry. Acta Diabetol 2021;58:1225-36.
14. Moore MC, Coate KC, Winnick JJ, An Z, Cherrington AD. Regulation of hepatic glucose uptake and storage in vivo. Adv Nutr 2012;3:286–94.
15. Lin HV, Accili D. Hormonal regulation of hepatic glucose production in health and disease. Cell Metab 2011;14:9–19.
16. World Health Organization. Classification of diabetes mellitus. Geneva: World Health Organization; 2019.
17. American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2021. Diabetes Care 2021;44 (Suppl 1):S15-S33.
18. Leslie RD, Palmer J, Schloot NC, Lernmark A. Diabetes at the crossroads: relevance of disease classification to pathophysiology and treatment. Diabetologia 2016;59:13–20.
19. De Sanctis V, Soliman A, Tzoulis P, Daar S, Karimi M, Yassin MA, et al. Clinical characteristics, biochemical parameters and insulin response to oral glucose tolerance test (OGTT) in 25 transfusion dependent β-thalassemia (TDT) patients recently diagnosed with diabetes mellitus (DM). Acta Biomed 2021;92 (6): e2021488.
20.Tzoulis P, Shah F, Jones R, Prescott E, Barnard M. Joint Diabetes Thalassaemia Clinic: An Effective New Model of Care, Hemoglobin 2014; 38:104-10.
21. Loebstein R, Lehotay DC, Luo X, Bartfay W, Tyler B, Sher GD. Diabetic Nephropathy in Hypertransfused Patients With β-Thalassemia: The role of oxidative stress. Diabetes Care 1998;21: 1306-9.
22. Tzoulis P. Review of endocrine complications in adult patients with β-thalassaemia major. Thal Rep 2014; 4:4871.
23. De Sanctis V, Incorvaia C, Soliman AT, Candini G, Pepe A, Kattamis C, et al. Does Insulin Like Growth Factor-1 (IGF-1) Deficiency Have a "Protective" Role in the Development of Diabetic Retinopathy in Thalassamia Major Patients? Mediterr J Hematol Infect Dis 2015;7:e2015038.
24. Bansal N. Prediabetes diagnosis and treatment: A review. World J Diabetes 2015;6:296-303.
25. Chatterton H, Younger T, Fischer A, Khunti K; Programme Development Group. Risk identification and interventions to prevent type 2 diabetes in adults at high risk: summary of NICE guidance. BMJ 2012;345: e4624.
26. Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes Canada 2018 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2018;42 (Suppl 1):S1–325.
27. Farmaki K, Angelopoulos N, Anagnostopoulos G, Gotsis E, Rombopoulos G, Tolis G. Effect of enhanced iron chelation therapy on glucose metabolism in patients with beta-thalassaemia major. Br J Haematol 2006;134:438-44.
28. Klonoff DC. Hemoglobinopathies and Hemoglobin A1c in Diabetes Mellitus. J Diabetes Sci Technol 2020;14:3-7.
29. De Sanctis V, Soliman AT, Daar S, Di Maio S, Elsedfy H, Kattamis C. For Debate: Assessment of HbA1c in Transfusion Dependent Thalassemia Patients. Pediatr Endocrinol Rev 2020;17:226-34.
30. Choudhary A, Giardina P, Antal Z, Vogiatzi M. Unreliable oral glucose tolerance test and HbA1C in Beta Thalassaemia Major-A case for continuous glucose monitoring? Br J Haematol 2013; 162:132-53.
31. Kattamis C, Delaporta P, Dracopoulou M, Paleologos G, Chrousos GP, Papassotiriou I, et al. Credibility of HbA1c in diagnosis and management of disturbances of glucose and diabetes in transfused patients with thalassemia. Riv Ital Med Adolesc 2014;12:65–71.
32. Liang Y, Bajoria R, Jiang Y, Su H, Pan H, Xia N, et al. Prevalence of diabetes mellitus in Chinese children with thalassaemia major. Trop Med Int Health 2017;22:716-24.
33. Rimondi F, Banin P, Gamberini MR, De Sanctis V. The continuous glucose monitoring system (CGMS) in patients with beta-thalassemia major and impaired glucose homeostasis: preliminary results. Pediatr Endocrinol Rev 2008; 6 (Suppl 1):190-2.
34. Soliman A, De Sanctis V, Yassin M, Elalaily R. Therapeutic Use and Diagnostic Potential of Continuous Glucose Monitoring Systems (CGMS) in Adolescents. Adv Diab Metab 2014; 2:21-30.
35. El-Samahy MH, Tantawy AA, Adly AA, Abdelmaksoud AA, Ismail EA, Salah NY. Evaluation of continuous glucose monitoring system for detection of alterations in glucose homeostasis in pediatric patients with β-thalassemia major. Pediatr Diabetes 2019;20:65-72.
36. Kattamis C, Ladis V, Skafida M, Iacovidou N, Theodoridis C. The different patterns of insulin response during Oral Glucose Tolerance Test (OGTT) in transfused young patients with β-Thalassemia. Acta Biomed 2021;92(4):e2021265.
37. 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.
38. Karadas N, Yurekli B, Bayraktaroglu S, Aydinok Y. Insulin secretion-sensitivity index-2 could be a novel marker in the identification of the role of pancreatic iron deposition on beta-cell function in thalassemia major. Endocr J 2019;66:1093-9.
39. Davidson MB. Counterpoint: the oral glucose tolerance test is superfluous. Diabetes Care 2002 ;25:1883-5.
40. Noetzli LJ, Mittelman SD, Watanabe RM, Coates TD, Wood JC. Pancreatic iron and glucose dysregulation in thalassemia major. Am J Hematol 2012;87:155-60.
41. Pepe A, Pistoia L, Gamberini MR, Cuccia L, Peluso A, Messina G, et al. The Close Link of Pancreatic Iron With Glucose Metabolism and With Cardiac Complications in Thalassemia Major: A Large, Multicenter Observational Study. Diabetes Care 2020; 43: 2830-9.
42. Guerrero-Romero F, Violante R, Rodríguez-Morán M. Distribution of fasting plasma glucose and prevalence of impaired fasting glucose, impaired glucose tolerance and type 2 diabetes in the Mexican paediatric population. Paediatr Perinat Epidemiol 2009;23:363-9.
43. Kwiatkowski JL. Management of transfusional iron overload - differential properties and efficacy of iron chelating agents. J Blood Med 2011;2:135-49.

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