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

Background: Prediabetes and diabetes mellitus (DM) are complications in adult patients with transfusion-dependent β-thalassemia (β-TDT), with their incidence increasing with age. Objective: This retrospective observational study describes the glycemic trajectories and evaluates predictive indices of β-cell function and insulin sensitivity/resistance in β-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 β-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 β-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 β-cell failure, peripheral resistance to insulin action, and reduced oDI and may be considered a relevant marker for incipient DM in β-TDT patients with prediabetes.