Post-Load Plasma Glucose Increase (PG-gap) as a Risk Factor for Developing Dysglycemia in Patients with...

Abnormal glucose homeostasis in transfusion-dependent β-thalassemia (β-TDT) patients requires early detection and intervention. However, current diagnostic criteria for patients with a normal oral glucose tolerance test (OGTT) may fail to detect a significant proportion of high-risk individuals.

The main objective of this study was to evaluate in β-TDT patients with normal fasting plasma glucose (FPG) and glucose tolerance (NGT), the plasma glucose (PG) incremental rise gap during OGTT, defined as the difference between 2h-PG and FPG (PG-gap), as an early predictor index associated with future risk of developing dysglycemia and thalassemia-related diabetes mellitus (Th-RDM).

58 β-TDT patients, recruited from three Thalassemia centers (Iran, Italy, and Greece), were selected for the study. The patients underwent a routine OGTT, and the PG-gap between 2-h PG and FPG (2-h PG - FPG) was calculated. The patients were categorized into three groups based on the results: "Low post-load" when the gap was < 20^th percentile (≤ 10 mg/dL), Group A; "Medium post-load" when the difference was distributed between the 20^th and < 75^th centiles (> 10 mg/dL and < 30 mg/d), Group B; and "High post load" ≥75^th percentile (≥ 30 mg/d) Group C.

Follow-up was available for 6 years in all 58 patients, including 8-year data in 45 patients. The incidence of dysglycemia, namely, isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), IFG plus IGT, isolated high 1-h PG (>155 mg/dL), after OGTT, and thalassemia-related diabetes mellitus (Th-RDM), was significantly lower in Groups A and B (27/45 patients) compared to Group C (18/45 patients) (χ²: 4.8214; P=0.028). Three patients in group C ("High post-load gap") developed Th-RDM. At the last evaluation, the serum ferritin (SF) level was < 800 μg/L in 13/45 (28.8%) patients, between ≥ 800 μg/L and < 1,500 μg/L in 17/45 (37.7%) patients, between ≥ 1,500 μg/L and < 3,000 μg/L in 14/45 (31,1%) patients, and ≥ 3,000 μg/L in 1/45 (2.3%) patients. Multiple linear regression was used to determine the variables contributing to the 2h-PG at the last follow-up. Only two variables, SF and age, were significantly associated with 2h-PG at last follow-up (t-stat: 2.3941; P=0.0203 and t-stat: 2.0918; P=0.0414, respectively). The other variables [BMI, pre-transfusional hemoglobin level, serum alanine aminotransferase (ALT), and positive family history for diabetes type 1 or 2 did not contribute significantly.

The findings suggest that a high post-load plasma glucose gap (≥ 75^th percentile or ≥ 30 mg/dL) is associated with a progressively increasing risk of glucose dysregulation over the next 6 to 8 years. These findings underscore the importance of a personalized approach to assessing the risk of early glucose metabolic disorders in β-TDT patients who are typically classified as normoglycemic.