Can we Predict Incipient Diabetes Mellitus in Patients with Transfusion Dependent - Thalassemia (-TDT) Referred with a History of Prediabetes?

Background: Prediabetes and diabetes mellitus (DM) are complications in adult patients with transfusion-dependent beta-thalassemia (beta-TDT), with their incidence increasing with age.Objective: This retrospective observational study describes the glycemic trajectories and evaluates predictive indices of beta-cell function and insulin sensitivity/resistance in beta-TDT patients with prediabetes, both in a steady state and during 3-h oral glucose tolerance test (OGTT), in order to identify patients at high risk for incipient diabetes.Setting: The study was mainly conducted at the Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara (Italy), in collaboration with thalassemia referring centers across Italy.Patients: The study included 11 beta-TDT (aged 15.11-31.10 years) with prediabetes.Methods: The ADA criteria for the diagnosis of glucose dysregulation were adopted. Investigations included evaluating plasma glucose levels and insulin secretion, analyzing glycemic trajectories and indices of beta-cell function, and insulin sensitivity/ resistance assessed in steady state and during OGTT.Results: The duration of progression from prediabetes to DM, expressed in years, showed a positive direct correlation with corrected insulin response (CIR-30 = r: 0.7606, P: 0.0065), insulinogenic index (IGI 0-120 = r: 0.6121, P:0.045), oral disposition index (oDI = r: 0.7119, P:0.013), insulin growth factor-1 (IGF-1= r: 0.6246, P: 0.039) and an inverse linear correlation with serum ferritin (SF = r:-0.7197, P: 0.012). The number of patients with 1-hour post-load PG value >= 155 mg/dL ( >= 8.6 mmol/L) was at-4 years: 4/9 (44.4%);-3 years: 8/9 (88.8%); -2 years: 7/10 (70 %) and at-1 year: 11/11 (100%) (PG range:162-217 mg/dL).Conclusions: A progressive increase in 1-hour PG in response to OGTT is associated with progressive beta-cell failure, peripheral resistance to insulin action, and reduced oDI and may be considered a relevant marker for incipient DM in beta-TDT patients with prediabetes.