Evolution of Combined Impaired Fasting Glucose and Impaired Glucose Tolerance in β-Thalassemia Major: Results in 58 Patients with a Mean 7.7- year Follow-Up: Evolution of prediabetes in β-Thalassemia Major

Evolution of Combined Impaired Fasting Glucose and Impaired Glucose Tolerance in β-Thalassemia Major: Results in 58 Patients with a Mean 7.7- year Follow-Up

Evolution of prediabetes in β-Thalassemia Major


  • Vincenzo De Sanctis Quisisana Hospital, Ferrara
  • Shahina Daar Department of Haematology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Sultanate of Oman
  • Ashraf T Soliman Department of Pediatrics, Division of Endocrinology, Hamad General Hospital, Doha, Qatar and Department of Pediatrics, Division of Endocrinology, Alexandria University Children’s Hospital, Alexandria, Egypt
  • Ploutarchos Tzoulis Department of Diabetes and Endocrinology, Whittington Hospital, University College London, London, UK
  • Mohamed A. Yassin National Center for Cancer Care and Research, Medical Oncology Hematology Section HMC, Doha, Qatar
  • Christos Kattamis First Department of Paediatrics, National Kapodistrian University of Athens 11527, Greece


β- thalassemia major, prediabetes, combination IFG/IGT, follow-up, iron overload, liver enzymes


Abstract. Background: Advances in β- thalassemia major (β-TM) care have transformed a disease which had previously led to an early childhood death into a chronic condition. With increased lifespan, comorbidities associated with the disease have become more common, among them glucose dysregulation (GD) which develops insidiously, aggravating prognosis and patients’ quality of life. Objectives: The objectives of this study were to retrospectively review the extent to which β-TM patients, having combined impaired fasting glucose (IFG) and impaired glucose tolerance test (IGT) on oral glucose tolerance test (OGTT), progressed to diabetes and to analyze the potential determinants inducing this progression, or regression to normal glucose tolerance test (NGT). Research design and method: Data of 58 β-TM patients, followed for a mean duration of 7.7 years (range: 1-20 years) with annual or biennial OGTT, were retrieved. Insulin release and insulin sensitivity (IS) were also analyzed. Results: During the follow-up, FPG and 2-h PG levels after OGTT reverted to NGT in 13 patients (22.4%), deteriorated in 13 patients (22.4%) who developed diabetes mellitus, and did not change in the remaining 32 patients (55.2%). A significant correlation was observed between FPG and ALT level (r: 0.3158; P:0.01) and an inverse correlation was found between chronological age and serum ferritin (SF) level (r: -0.321; P:0.014). Finally, SF and ALT, both at the baseline and at the time of last observation, were independent predictors of evolution to diabetes mellitus. Conclusion: The combination IFG/IGT in β-TM patients with severe iron overload constitutes a high-risk state for developing diabetes.



Ladis V, Chouliaras G, Berdousi H, Kanavakis E, Kattamis C. Longitudinal study of survival and causes of death in patients with thalassemia major in Greece. Ann N Y Acad Sci 2005;1054:445–50.

De Sanctis V, Soliman AT, Elsedfy H, Pepe A, Kattamis C, El Kholy M, et al. Diabetes and Glucose Metabolism in Thalassemia Major: An Update. Expert Rev Hematol 2016;9:401–8.

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.

American Diabetes Association. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes - 2020. Diabetes Care 2020;43(Suppl 1):S14–S31.

World Health Organization. Classification of diabetes mellitus. Geneva:World Health Organization; 2019.

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.

Tabak A G, Herder C, Rathmann W, Brunner EJ, Kivimaki M. Prediabetes: A high-risk state for diabetes development. Lancet 2012; 379:2279–90.

Qiao Q, Lindstrom J, Valle TT, Tuomilehto J. Progression to clinically diagnosed and treated diabetes from impaired glucose tolerance and impaired fasting glycaemia. Diabet Med 2003;20:1027–33.

Færch K, Borch-Johnsen K, Holst JJ, Vaag A. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes? Diabetologia 2009;52:1714–23.

Lecube A, Hernández C, Simó R. Glucose abnormalities in non-alcoholic fatty liver disease and chronic hepatitis C virus infection: the role of iron overload. Diabetes Metab Res Rev 2009;25:403-10.

Rhee SY, Woo JT, Chon S, Hwang YC, Oh S, Ahn KJ, et al. Characteristics of insulin resistance and insulin secretory capacity in Korean subjects with IFG and IGT. Diabetes Res Clin Pract 2010;89250-5.

Pratley RE, Weyer C. Progression from IGT to type 2 diabetes mellitus: the central role of impaired early insulin secretion. Curr Diab Rep 2002;2:242-8.

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: Pancreatic changes and glucose homeostasis in β-thalassemia. Acta Biomed 2021;14;92(3):e2021232.

Platis O, Anagnostopoulos G, Farmaki K, Posantzis M, Gotsis E, Tolis G. Glucose metabolism disorders improvement in patients with thalassaemia major after 24-36 months of intensive chelation therapy. Pediatr Endocrinol Rev 2004;2 (Suppl 2):279-81.

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.

Munkongdee T, Chen P, Winichagoon P, Fucharoen S, Paiboonsukwong K. Update in Laboratory Diagnosis of Thalassemia. Front Mol Biosci 2020;7:74.

Styne DM, Arslanian SA, Connor EL, Farooqi IS, Murad MH, Silverstein JH, et al. Pediatric Obesity-Assessment, Treatment, and Prevention:An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2017;102:709-57.

De Sanctis V, Soliman AT, Elsedfy H, Skordis N, Kattamis C, Angastiniotis M, et al. Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines. Indian J Endocrinol Metab 2013;17:8-18.

De Sanctis V, Elsedfy H, Soliman AT, Elhakim IZ, Kattamis C, Soliman NA, et al. Clinical and biochemical data of adult thalassemia major patients (TM) with multiple endocrine complications (MEC) versus TM patients with normal endocrine functions: a long-term retrospective study (40 years) in a tertiary care center in Italy. Mediterr J Hematol Infect Dis 2016;8(1):e2016022.

De Sanctis V, Gamberini MR, Borgatti L, Atti G, Vullo C, Bagni B. Alpha and beta cell evaluation in patients with thalassaemia intermedia and iron overload. Postgrad Med J 1985;61:963-7.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–9.

Matsuda M, De Fronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999;22:1462–70.

Bahar A, Kashi Z, Sohrab M, Kosaryan M, Janbabai G. Relationship between beta-globin gene carrier state and insulin resistance. J Diabetes Metab Disord 2012;11(1):22.

Kernan WN, Inzucchi SE, Viscoli CM, et al. Pioglitazone improves insulin sensitivity among nondiabetic patients with a recent transient ischemic attack or ischemic stroke. Stroke 2003;34:1431–6.

Utzschneider K, Prigeon R, Faulenbach M V, Tong J, Carr DB, Boyko EJ, et al. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care 2009;32:335-41.

Alder R, Roesser EB. Introduction to probability and statistics. WH Freeman and Company Eds. Sixth Edition. San Francisco (USA),1975.

Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R, et al. Expert committee on the diagnosis and classification of diabetes mellitus: follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003;26:3160–7.

Gabir MM, Hanson RL, Dabelea D, Imperatore G, Roumain J, Bennett PH, et al. Plasma glucose and prediction of microvascular disease and mortality: evaluation of 1997 American Diabetes Association and 1999 World Health Organization criteria for diagnosis of diabetes. Diabetes Care 2000;23:1113–8.

Larson H, Lindgarde F, Berglund G, Ahrén B. Prediction of diabetes using ADA or WHO criteria in post-menopausal women: a 10-year follow-up study. Diabetologia 2004;43:1224–8.

Vaccaro O, Ruffa G, Imperatore G, Iovino V, Rivellese AA, Riccardi G. Risk of diabetes in the new

diagnostic category of impaired fasting glucose: a prospective analysis. Diabetes Care 1999;22:1490–

De Sanctis V, Soliman AT, Tzoulis P, Daar S, Di Maio S, Fiscina B, Kattamis C. 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.

Kattamis C, Ladis V, Tsoussis D, Kaloumenou I, Theodoridis C. Evolution of glucose intolerance and diabetes in transfused patients with thalassemia. Pediatr Endocrinol Rev 2004;2 (Suppl 2):267-71.

World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. Report of a WHO/IDF Consultation. Geneva; 2006

Cuschieri S, Grech S. Assessing impaired fasting blood glucose criteria for high-risk dysglycaemic populations: an experience from a European population state. J Diabetes Metab Disord 2020;19:775-81.

Taher AT, Saliba AN. Iron overload in thalassemia: different organs at different rates. Hematology Am Soc Hematol Educ Program 2017;2017:265-71.

Cappellini MD, Cohen A, Porter J, Taher A, and Viprakasit V Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). 3rd ed. Nicosia, Cyprus: Thalassaemia International Federation; 2014.

Wood JC. Magnetic resonance imaging measurement of iron overload. Curr Opin Hematol 2007;14(3): 183–90.

Prabhu R, Prabhu V, Prabhu RS. Iron overload in beta thalassemia: a review. J Biosci Tech 2009;1:20–31.

Manley SE, Luzio SD, Stratton IM, Wallace TM, Clark PM. Preanalytical, analytical, and computational factors affect homeostasis model assessment estimates. Diabetes Care 2008;31:1877-83.

Kang ES, Yun YS, Park SW, Kim HJ, Ahn CW, Song YD, et al. Limitation of the validity of the homeostasis model assessment as an index of insulin resistance in Korea. Metabolism 2005;54206-11.

Merkel PA, Simonson DC, Amiel SA, Plewe G, Sherwin RS, Pearson HA, et al. Insulin resistance and hyperinsulinemia in patients with thalassemia major treated by hypertransfusion. N Engl J Med1988;318: 809-14.

Suvarna J, Ingle H, Deshmukh CT. Insulin resistance and beta cell function in chronically transfused patients of thalassemia major. Indian Pediatr 2006;43:393-400.

Hafez M, Youssry I, El-Hamed FA, Ibrahim A. Abnormal glucose tolerance in beta-thalassemia: assessment of risk factors. Hemoglobin 2009;33:101-8.

Ghergherehchi R, Habibzadeh A. Insulin resistance and β cell function in patients with β-thalassemia major. Hemoglobin 2015;39:69-73.

DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979;237:E214–E23.







How to Cite

De Sanctis V, Daar S, Soliman AT, Tzoulis P, Yassin MA, Kattamis C. Evolution of Combined Impaired Fasting Glucose and Impaired Glucose Tolerance in β-Thalassemia Major: Results in 58 Patients with a Mean 7.7- year Follow-Up: Evolution of prediabetes in β-Thalassemia Major . Acta Biomed [Internet]. 2022 Jul. 1 [cited 2024 Jul. 13];93(3):e2022242. Available from: https://www.mattioli1885journals.com/index.php/actabiomedica/article/view/12825