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

Background: Glucose dysregulation (GD), including prediabetes and diabetes mellitus (DM), is a common complication of transfusion-dependent beta-thalassemia (TDT) patients. The prevalence increases with age and magnitude of iron overload, affecting a significant proportion of patients. According to the international guidelines, the development of GD is frequently asymptomatic. Therefore, an early diagnosis 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 beta-cell function, insulin sensitivity, and insulin secretion were calculated. Results: At baseline, 18 TDT patients had normal glucose tolerance (NGT) and 10 had isolated impaired fasting glycemia (IFG), according to the American Diabetes Association (ADA) criteria. Compared to 18 healthy prepubertal 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, nil, and DI) but one [insulinogenic index (IGI)] were statistically different in TDT patients with GD compared to controls. Conclusion: This study underlines the concept that the spectrum of glucose tolerance in TDT patients represents a continuum of glucose homeostasis disturbances and that prepubertal patients with IFG are at higher risk of developing a further deterioration of glucose metabolism with time. Moreover, it appears that one-third of adult TDT patients with normal fasting glucose may develop GD in the second-third decade of life. Thus, early intervention could help to prevent an expected further decline of glucose tolerance.