THE PERFORMANCE OF HOMA 2 COMPARED TO DYNAMIC MARKERS OF INSULIN SECRETION AND SENSITIVITY/RESISTANCE FOR PREDICTING DYSGLYCEMIA IN TRANSFUSION-DEPENDENT Β-THALASSEMIA: THE EXPERIENCE OF A SINGLE CENTRE
HOMA 2 and DYNAMIC MARKERS OF INSULIN SECRETION FOR PREDICTING DYSGLYCEMIA in TDT
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Background. Screening for dysglycemia with an annual oral glucose tolerance test (OGTT) is recommended in transfusion-dependent β-thalassemia (β-TDT), but adherence in routine practice is low. Fasting surrogate indices of β-cell function and insulin sensitivity could offer a less burdensome alternative.
Aims. To evaluate in adult β-TDT patients with normal fasting plasma glucose (FPG < 100 mg/dL): (i) the performance of fasting HOMA-2 indices (HOMA2-IR, HOMA2-%β, HOMA2-%S) and their disposition index as predictors of dysglycemia, and (ii) the comparative value of basal versus dynamic OGTT-derived markers (30-min and 1-h plasma glucose, insulinogenic index [IGI], IGI × ISI Matsuda index and IGI/HOMA2-IR), as predictors of hyperglycemia.
Methods. A single-centre retrospective analysis of 42 β-TDT patients (19 males / 23 females; mean age 29.2 ± 5.9 yr) with FPG < 100 mg/dL who underwent a standard 75-g 2-h OGTT between January 2011 and September 2025. Patients were classified as those with normal glucose tolerance (NGT; n = 19) or those with impaired glucose tolerance (IGT: n= 20) or thalassemia-related diabetes mellitus (Th-RDM: n = 3). Fasting and dynamic indices were compared by ANOVA and Mann–Whitney U; associations were tested by Pearson/Spearman correlation and by three sequential multivariable linear regression models with 2-h plasma glucose as the dependent variable. ROC analysis with Youden's index identified optimal cut-offs.
Results. Fasting HOMA2-IR, HOMA2-%β and HOMA2-%S did not differ significantly between NGT and hyperglycemic patients and were not independent predictors of 2-h plasma glucose. In contrast, in the total group, 30-min PG, 1-h PG, IGI, IGI × ISI Matsuda index and IGI/HOMA2-IR all differed significantly between groups (p: ≤ 0.0082) and were inversely correlated with 2-h PG. Receiver operating characteristic (ROC) analysis and area under the curve (AUC-ROC) were used to assess diagnostic performance of the most significant variables The ROC-AUC cut-offs for predicting dysglycemia were 122.5 mg/dL for 30-min PG (sensitivity 0.91, specificity 0.52), 134 mg/dL for 1-h PG (0.95, 0.10), 5.7 for IGI × ISI Matsuda index (0.87, 0.47) and 1.33 for IGI/HOMA2-IR (0.87, 0.57).
Conclusions. Fasting HOMA-2 indices alone are not reliable predictors of dysglycemia in β-TDT patients with PG < 100 mg/dL. The dynamic IGI/HOMA2-IR ratio and the 30-min/1-h post-load plasma glucose may be used to stratify patients at high risk of glucose dysregulation and could minimize reliance on the full annual OGTT. Larger, prospective multicentre studies are needed to validate these cut-offs.
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Dysglycemia, screenin, thalassemiaSupporting Agencies
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