POST-LOAD PLASMA GLUCOSE INCREASE (PG-GAP) AS A RISK FACTOR FOR DEVELOPING DYSGLYCEMIA IN PATIENTS WITH TRANSFUSION-DEPENDENT Β-THALASSEMIA (Β-TDT): RETROSPECTIVE ANALYSIS OVER 8 YEARS

Abstract. Background: Glucose dysregulation (GD) in transfusion-dependent β-thalassemia (β-TDT) patients demands early detection and intervention. However, current diagnostic criteria of patients with a normal oral glucose tolerance test (OGTT) may fail to detect all high-risk individuals. Objectives: Our objective was to evaluate the incremental rise gap in plasma glucose (PG) during oral glucose tolerance tests (OGTTs), defined as the difference between 2h-PG and fasting PG, as a predictor for the future risk of developing glucose dysregulation (GD) and overt diabetes in patients with transfusion-dependent β-thalassemia (β-TDT) with normal glucose tolerance (NGT) . Research design and methods: 58 β-TDT patients, recruited from three Thalassemia centers (Iran, Italy and Greece), were selected for the study. β-TDT patients were categorized into three groups, based on the difference between 2 h-PG and FPG (2 h-PG – FPG): "Low post-load", when the gap (2-h PG mg/dL - FPG ) was < 20th percentile ( < 10 mg/dL) Group A; "Medium post-load and High post-load" groups, when the differences was distributed between 20th and <75th centile (> 10 mg/dL and < 30 mg/dL (Group B). and ≥75th percentile ( ≥ 30 mg/dL; Group C.). Results: In all 58 β-TDT patients, follow-up was available for 6-years and in 45 patients for 8 years within 2 years interval. The incidence of GD, [isolated high 1-h PG (>155 mg/dL) and Th-RD], after an 8-year follow-up, was significantly lower in Groups A and B (27/45 patients) compared to Group C (18/45 patients) (χ2: 4.8214;P:0.028). Noteworthy, three patients of group C ("High post-load gap") developed thalassemia-related diabetes mellitus (Th-RDM). At last evaluation in 13/45 (28.8%) patients the SF level was < 800 µg/L, in 17/45 (37.7%) between ≥ 800 µg/L and < 1,500 µg/L, in 14/45 (31,1 %) between ≥ 1,500 µg/L and < 3,000 µg/L, and in 1/45 (2.3%) ≥ 3,000 µg/L. Conclusions: Our findings suggest that a high rise of postload plasma glucose gap, above 10 mg/dL, is associated with a progressively increased risk of glucose dysregulation over the next 6- 8-year period. These findings highlight the need for a personalized approach to assess the risk of early glucose metabolic disorders in β-TDT patients who are traditionally classified as normoglycemic.

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