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

ABSTRACT

Background: Prediabetes and diabetes mellitus (DM) are complications in adult patients with transfusion-dependent ß-thalassemia (ß-TDT), with their incidence increasing with age. Objective: This retrospective observational study describes the glycemic trajectories and evaluates predictive indices of ß-cell function and insulin sensitivity/resistance in ß-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 ß-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 ß-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, P0.045), oral disposition index (oDI = r 0.7119, P0.013), 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 range162-217 mg/dL). Conclusions: A progressive increase in 1-hour PG in response to OGTT is associated with progressive ß-cell failure, peripheral resistance to insulin action, and reduced oDI and may be considered a relevant marker for incipient DM in ß-TDT patients with prediabetes.