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

Abstract

Prediabetes and diabetes mellitus (DM) are complications in adult patients with transfusion-dependent β-thalassemia (β-TDT), with their incidence increasing with age. 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. The study was mainly conducted at the Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara (Italy), in collaboration with thalassemia referring centers across Italy. 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. 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). 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.