FASTING PLASMA GLUCOSE LEVELS WITHIN THE HIGH NORMAL RANGE ARE ASSOCIATED WITH A SIGNIFICANTLY INCREASED RISK OF FUTURE DYSGLYCEMIA IN TRANSFUSION-DEPENDENT Β THALASSEMIA: A DECADE-LONG MULTICENTER RETROSPECTIVE ANALYSIS Higher normal fasting plasma glucose and glucose dysregulation in β- thalassemia
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Keywords
Transfusion-dependent β-thalassemia, higher normal fasting plasma glucose, glucose dysregulation, fasting plasma glucose trajectories, risk factors, long-term follow-up
Abstract
Abstract. Objective: To evaluate the risk of developing glucose dysregulation and diabetes mellitus over a 10-year period among transfusion-dependent β-thalassemia (β-TDT) patients with varying levels of fasting plasma glucose (FPG) within the normoglycemic range.
Setting: The study included β-TDT patients followed from January 2014 to January 2025 in three thalassemia canters; Tehran and Shiraz in Iran, and Ferrara in Italy.
Participants: A total of 238 β-TDT patients (age range: 10–41.9 years; 96 males and 142 females) were included.
Results: At baseline, the mean fasting plasma glucose (FPG) level was 88.0 ± 8.3 mg/dL (median: 90 mg/dL), and the mean serum ferritin (SF) level was 2,080 ± 2,072 µg/L (median: 1,368 µg/L). The mean alanine aminotransferase (ALT) level, available in 201/238 patients, was 29.0 ± 25.8 IU/L. β-TDT patients were categorized into three subgroups according to the conversion of FPG during the 10 year follow up [Group A: 93/238 β-TDT patients with persistent normal FPG according to ADA criteria; Group B: 67/238 patients developed persistent impaired fasting glucose (IFG), and Group C: 78/238 patients developed thalassemia-related diabetes mellitus (Th-RDM)]. Notably, 64.1% and 76.9 of patients with FPG at baseline ≥ 90 mg/dl and < 100 mg/dL developed impaired fasting glucose (Group B) and Th-RDM (Group C), respectively. To determine the optimal cutoff for the risk of progressing to impaired fasting glucose (IFG) and Th-RDM at 10-year follow-up, ROC curve analyses and respective areas under the curve were analyzed. The FPG cutoff value for optimal specificity and sensitivity was established at 87.5 mg/dL. Contributing factors associated with the progression to prediabetes and Th-RDM included: older age, gender (females), positive family history of type 1 or type 2 diabetes, lower pre-transfusion hemoglobin levels, severity of iron overload, and elevated liver enzyme levels.
Conclusions: Higher FPG levels within the normoglycemic range in β-TDT patients are associated with a greater risk for future glucose dysregulation and diabetes. Close monitoring and timely intervention in these high-risk individuals should be considered in order to reduce the burden of hyperglycemia in this population.
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