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 Long-term retrospective analysis of glucose homeostasis in children with transfusion dependent β-thalassemia
Main Article Content
Keywords
Thalassemia, iron overload, oral glucose tolerance test, type 2 diabetes mellitus, insulin secretion and sensitivity indices, long-term follow-up.
Abstract
Background: Glucose dysregulation (GD), including prediabetes and diabetes mellitus (DM), is a common complication of transfusion dependent β-thalassemia (TDT) patients. The prevalence increases with age and magnitude of iron overload, affecting a significant proportion of patients. The development of GD is frequently asymptomatic and therefore an early diagnosis, according to the international guidelines, requires an annual oral glucose tolerance test (OGTT) in all TDT patients aged ten years or older.
Purpose: This retrospective study aims to evaluate the prevalence of GD in a homogenous population of prepubertal TDT patients and to enhance understanding of the pathogenesis and progression of glucose homeostasis in this group of patients.
Methods: A selected group of 28 TDT patients was followed for at least 10.3 years (range: 10.3 - 28.10 years) from prepubertal age (mean 11.0 ± standard deviation 1.1 years) to adulthood (28.7 ± 3.7 years). Glucose tolerance and insulin response to OGTT were assessed, and indices of β-cell function, insulin sensitivity and insulin secretion were calculated.
Results: At baseline, 18 TDT patients had normal glucose tolerance (NGT) and 10 isolated impaired fasting glycaemia (IFG), according to the American Diabetes Association (ADA) criteria. Compared to 18 prepubertal healthy controls (mean ± SD age: 10.9 ± 1.1 years), the fasting plasma glucose (FPG), basal insulin level and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index were significantly higher in the group of TDT patients (p= 0.001, 0.01 and 0.012, respectively). At the last observation, 7/18 patients (38.8%) with NGT and 9/10 (90%) with IFG at baseline deteriorated; 3 female patients developed type 2 DM (1 from the NGT group and 2 from the IFG group). Compared to adult controls, TDT patients with NGT had a reduced oral disposition index (DI) (p= 0.006), but no significant difference in HOMA-IR and Matsuda index. Conversely, all insulin indices (HOMA-IR, MI and DI) but one [insulinogenic index (IGI)] were statistically different in TDT patients with GD compared to controls.
Conclusion: This study shows a spectrum of disturbances in glucose homeostasis among TDT patients and that prepubertal patients with IFG are at higher risk for developing a deterioration of glucose metabolism.
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23. 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;28:412-419. PMID: 3899825 DOI: 10.1007/BF00280883.
24. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22:1462–1470. PMID: 10480510 DOI: 10.2337/diacare.22.9.1462.
25. Utzschneider K, Prigeon R, Faulenbach M V, Tong J, Carr DB, Boyko EJ, Leonetti DL, McNeely MJ, Fujimoto WY, Kahn SE. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care. 2009;32:335-341. DOI:10.2337/dc08-1478. Erratum in: Diabetes Care. 2009;32:1355. PMID: 18957530.
26. Retnakaran R, Shen S, Hanley AJ, Vuksan V, Hamilton JK, Zinman B. Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test. Obesity (Silver Spring). 2008;16:1901–1907. PMID:18551118 DOI: 10.1038/oby.2008.307.
27. Alder R, Roesser EB. Introduction to probability and statistics.WH Freeman and Company Eds. Sixth Edition. San Francisco (USA), 1975.PMID:1674139.
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De Sanctis, V. (2021) “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: Long-term retrospective analysis of glucose homeostasis in children with transfusion dependent β-thalassemia”, Mediterranean Journal of Hematology and Infectious Diseases, 13(1), p. e2021051. doi: 10.4084/MJHID.2021.051.
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